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13,800 | 26,776,826 | Nerve sparing radical hysterectomy is associated with reduced lower urinary tract dysfunction . | INTRODUCTION Radical hysterectomy represents the cornerstone in the management of localized cervical cancer .
Despite its oncologic efficacy , radical hysterectomy is associated with a significant amount of complications and a negative impact on quality of life .
Surgical technique seems to influence the functional outcomes .
AIM OF THE STUDY A systematic review to provide an up date on the lower urinary tract dysfunction following nerve sparing radical hysterectomy . | OBJECTIVES The objectives of this study were to describe our laparoscopic nerve-sparing radical hysterectomy ( LNSRH ) technique and to assess the feasibility and safety of the procedure , as well as its impact on voiding function . We introduce a fascia space dissection technique in order to preserve the pelvic splanchnic nerve , the hypogastric nerve and the bladder branch of the inferior hypogastric plexus under magnification ( ×10.5 ) during laparoscopic radical hysterectomy ( LRH ) with pelvic lymphadenectomy . METHODS From October 2006 to November 2009 , 163 consecutive patients with cervical cancer underwent laparoscopic radical hysterectomy ( LRH ) and pelvic lymphadenectomy , with 82 women undergoing LNSRH with fascia space dissection technique ( LNSRH group ) and 81 undergoing LRH ( LRH group ) . Data from 163 patients were prospect ively collected and compared . Post-operative assessment of bladder function included the following : the time to recover the ability to void spontaneously and to achieve a post-void residual urine ( PVR ) volume of less than 50 ml , with urination function grade d. RESULTS The laparoscopic nerve-sparing radical hysterectomy procedure was completed successfully and was conducted safely in all of the patients . There were no conversions to open surgery in the two groups . The median operative duration in the LNSRH and the LRH groups were 163.52±34.47 min and 132.13±31.42 min , respectively . Blood loss was 142.12±62.38 ml and 187.69±68.63 ml , respectively . The time taken to obtain a post-void residual urine volume of less than 50 ml after removal of the urethral catheter was 7.42±2.35 d ( 5 - 18 d ) in LNSRH group and was 16.75±7.73 d ( 5 - 35 d ) in LRH group ( P<0.05 ) . The bladder void function recovery to Grade s 0-I was 76 ( 92.7 % ) for the LNSRH group and 59 ( 72.8 % ) for the LRH group . A mean follow-up of 22.3 ( 5 - 42 ) months was adhered to , and no patient had a recurrence or metastasis . CONCLUSIONS The technique described in this preliminary study appears to be safe , feasible , and easy in our population , with satisfactory recovery of voiding function STUDY OBJECTIVE To compare laparoscopic modified radical hysterectomy ( LMRH ) with traditional modified radical hysterectomy ( MRH ) in women with early invasive cervical cancer . DESIGN Prospect i ve , nonr and omized study ( Canadian Task Force classification II-1 ) . SETTING Chi Mei Foundation Medical Center , Tainan , Taiwan . PATIENTS Ten women with cervical cancer stage Ia2 to Ib1 ( < /=2 cm ) . Intervention . LMRH ( class II radical hysterectomy ) and pelvic lymphadenectomy . MEASUREMENTS AND MAIN RESULTS The pathologist examined all specimens . The width of parametrium ( mean + /- SD ) was 1.75 + /- 0.68 cm on the right and 1.70 + /- 0.54 cm on the left . The length of the vaginal cuff was 1.37 + /- 0.86 cm . Operating time for LMRH ( 159 + /- 26.4 min ) was similar to that for MRH ( 165.7 + /- 30.5 min ) . Postoperative hospitalization for LMRH ( 4.1 + /- 1.5 days ) and estimated blood loss ( 250 + /- 147.2 ml ) were significantly less than for MRH ( 8.3 + /- 4.4 days and 611.5 + /- 256.8 ml , respectively ) . No intraoperative complications occurred , and no patient experienced postoperative voiding dysfunction or constipation . CONCLUSIONS Based on preliminary results , LMRH is feasible for treatment of early invasive cervical cancer , and may become preferred for surgical staging of the disease Background R and omised Controlled Trials ( RCTs ) are the preferred study design when comparing therapeutical interventions in medicine . To improve clarity , consistency and transparency of reporting RCTs , the Consoli date d St and ards of Reporting Trials ( CONSORT ) statement was developed . Objectives ( 1 ) To assess the quality of reports and abstract s of RCTs in otorhinolaryngologic literature by using CONSORT checklists , ( 2 ) to compare the quality of reports and abstract s of otorhinolaryngologic RCTs between the top 5 general medical journals and top 5 otorhinolaryngologic journals , and ( 3 ) to formulate recommendations for authors and editors of otorhinolaryngologic ( ‘ ENT ’ ) journals . Methods Based on 2012 ISI Web of Knowledge impact factors , the top 5 general medical and ENT journals were selected . On 25 June 2014 , using a highly sensitive Cochrane RCT filter and ENT filter , possibly relevant articles since January 1st , 2010 were retrieved and relevant RCTs were selected . We assessed how many CONSORT items were reported adequately in reports and abstract s and compared the two journal types . Results Otorhinolaryngologic RCTs ( n = 15 ) published in general medical journals reported a mean of 92.1 % ( 95 % confidence interval : 89.5%–94.7 % ) of CONSORT items adequately , whereas RCTs ( n = 18 ) published in ENT journals reported a mean of 71.8 % ( 66.7%–76.8 % ) adequately ( p < 0.001 ) . For abstract s , means of 70.0 % ( 63.7%–76.3 % ) and 32.3 % ( 26.6–38.0 % ) were found respectively ( p < 0.001 ) . Large differences for specific items exist between the two journal types . Conclusion The quality of reporting of RCTs in otorhinolaryngologic journals is suboptimal . RCTs published in general medical journals have a higher quality of reporting than RCTs published in ENT journals . We recommend authors to report their trial according to the CONSORT Statement and advise editors to endorse the CONSORT Statement and implement the CONSORT Statement in the editorial process to ensure more adequate reporting of RCTs and their abstract OBJECTIVE To investigate bladder and intestinal function recovery and quality of sexual life after laparoscopic nerve-sparing radical hysterectomy ( LNRH ) for treatment of early invasive cervical carcinoma . METHODS Subjects included patients who underwent radical hysterectomy by laparotomy who were r and omly assigned to 2 groups : 30 patients who underwent LNRH and 35 classical laparoscopic radical hysterectomy ( LRH ) . We assessed the patients general clinical information , surgical characteristics , pathological findings , and adjuvant therapies . A urodynamic study was used to assess bladder function . Intestinal function recovery and quality of sexual life were evaluated by question naire . RESULTS No significant differences were found in age , surgery characteristics , pathological findings , adjuvant therapies , and main adverse effects between the 2 groups . The mean duration of the postoperative catheterization ( DPC ) in group LNRH was shorter than that in group LRH ( P < 0.001 ) . The maximum flow rate , maximum cystometric capacity , maximum detrusor pressure and urinary complications in group LNRH were better than those in group LRH . The quality of sexual life evaluated according to the female sexual function index ( FSFI ) was better in group LNRH than in those who underwent LRH . The intestinal function of patients in group LNRH also recovered better compared with patients in group LRH Background Nerve‐sparing radical hysterectomy ( NSRH ) was developed in an attempt to minimize complications after radical hysterectomy . Since 2008 , a modified NSRH‐nerve plane‐sparing radical hysterectomy ( NPSRH ) has been developed at the Cancer Hospital , Chinese Academy of Medical Sciences . The aim of this study was to investigate the role of NPSRH in improving postoperative pelvic visceral dysfunctions . Methods Eighty‐three patients with International Federation of Gynecology and Obstetrics ( FIGO ) stage IB1‐IIA2 cervical cancer received NPSRH ( the study group ) from January 2008 to October 2012 . One hundred and sixty‐six patients who underwent conventional radical hysterectomy ( CRH ) were r and omly selected as the control group . Age , pathological type and stage were matched between the two groups . The safety of surgery was assessed by duration of operation and blood transfusion rate . Postoperative short‐term bladder function was analyzed by duration of catheterization . Long‐term bladder , anorectal and sexual function were evaluated with question naires . Results Seventy‐eight patients ( 94.0 % ) in the NPSRH group and one hundred and sixty patients ( 96.4 % ) in the CRH group completed the study . Median follow‐up time was 31.9 months and 31.0 months respectively ( P=0.708 ) . There was no significant difference between the two groups in terms of age , body mass index , FIGO stage , pathologic type , preoperative and postoperative therapy ( P > 0.05 ) . The blood transfusion rate shared no difference between two groups ( P=0.364 ) . The operation time in the NPSRH group was significantly longer than CRH group ( P < 0.01 ) . But the duration of catheterization and hospitalization in the NPSRH group was significantly reduced compared with CRH group ( P < 0.01 ) . In addition , the incidence of long‐term urinary frequency , urinary incontinence , urinary retention , straining to void , constipation and diarrhea was significantly lower in the NPSRH group ( P < 0.05 ) . However , there was no significant difference regarding sexual function ( P > 0.05 ) . Conclusions The current evidence indicated that NPSRH improved long‐term bladder function compared to CRH . Moreover , it may improve long‐term anorectal function as well The objective of this study is to describe a technique for preserving the autonomic nerve systematic ally , including the hypogastric nerves , pelvic splanchnic nerves , and pelvic plexus and its vesical branches , based on anatomic considerations for the autonomic nerves innervating the urinary bladder , in radical hysterectomies and to assess postsurgical bladder function . A nerve-sparing radical hysterectomy was carried out on 27 consecutive patients with uterine cervical cancer treated between 2000 and 2002 . The FIGO stages of the disease consisted of 10 stage Ib1 , 6 stage Ib2 , 3 stage IIa , and 8 stage IIb . The nerve-sparing procedure was successfully completed in 22 of the 27 patients ( 81.5 % ) in the study . At 1 year after the operation , bladder symptoms were significantly improved in the nerve-sparing group compared to the non – nerve-sparing group . Urinary incontinence and abnormal ( diminished ) bladder sensation were observed in three of the five patients ( two patients had both symptoms ) , for whom the nerve-sparing procedure could not be performed , but none of the 22 patients for whom the nerve-sparing procedure was performed had incontinence , and only two patients had abnormal ( increased ) bladder sensation ( P = 0.0034 for incontinence and P = 0.030 for abnormal bladder sensation ) . The patients ' survival was not adversely affected by the nerve-sparing procedure . Although it is still preliminary , the surgical technique described in this report is thought to be effective for preserving bladder function , and thus , the quality of life could be improved for patients with cervical cancer who are treated with a radical hysterectomy . For further evaluation of the efficacy of nerve-sparing radical hysterectomy , a prospect i ve r and omized trial needs to be performed OBJECTIVE To describe the anatomy of pelvic autonomic nerves as it applies to nerve-sparing radical hysterectomy , and the technique , feasibility , and results of robotic nerve-sparing radical hysterectomy . METHODS Prospect i ve evaluation of 6 patients undergoing robotic nerve-sparing radical hysterectomy ( type C1 ) for cervical cancer Stage IB ( 1B1 in 3 and 1B2 in 3 patients ) . Pelvic lymphadenectomy was performed in 3 patients and pelvic and aortic in the remaining 3 patients . RESULTS The operation was completed in all patients . The mean age of the patients was 51.0 ( range 33 - 73 ) and mean BMI 27.8 ( range 23.2 - 35.1 ) . The mean operating time was 238.6 min ( range 207 - 256 ) , mean blood loss 135 ml ( range 100 - 150 ) , mean number of lymph nodes was 23.6 ( range 19 - 29 ) , mean hospital stay was 2 days ( range 1 - 4 ) . There were no intraoperative complications . Postoperative complications occurred in 1 patient with an ileus who required an extended hospital stay . One patient did not regain normal urinary voidings until the fourth week after surgery . All patients remain free of disease . CONCLUSION Robotic nerve-sparing radical hysterectomy is safe and feasible . Urinary dysfunction may occur Objective Conventional radical hysterectomy with pelvic lymphadenectomy ( RHL ) for early-stage cervical cancer is associated with significant bladder , anorectal , and sexual dysfunction . Nerve-sparing modification of RHL ( NS-RHL ) has been developed with the aim to reduce surgical treatment-related morbidity . Postoperative radiation therapy ( RT ) is offered to patients with unfavorable prognostic features to improve local control . The aim of the study was to assess self-reported morbidity of various types of treatment in cervical cancer patients . Methods Self-reported symptoms were prospect ively assessed before and 1 and 2 years after treatment by the Dutch Gynaecologic Leiden Question naire . Results Included were 229 women ( 123 NS-RHL and 106 conventional RHL ) . Ninety-four ( 41 % ) received RT . Up to 2 years ( response rate , 81 % ) , women reported significantly more bowel , bladder , and sexual symptoms compared with the pretreatment situation . No significant difference was found between the conventional RHL and NS-RHL with the exception of the unexpected finding that a smaller percentage in the NS-RHL group ( 34 % vs 68 % ) complained about numbness of the labia and / or thigh . Radiation therapy had a negative impact on diarrhea , urine incontinence , lymphedema , and sexual symptoms ( especially a narrow/short vagina ) . Conclusions In the current longitudinal cohort study , treatment for early-stage cervical cancer was associated with worse subjective bladder , anorectal , and sexual functioning , irrespective of the surgical procedure used . Postoperative RT result ed in a significant deterioration of these functions . The results have to be interpreted with caution in view of the study design and method used Objective A prospect i ve , r and omized controlled trial was conducted to evaluate the efficacy of nerve-sparing radical hysterectomy ( NSRH ) in preserving bladder function and its oncologic safety in the treatment of cervical cancer . Methods From March 2003 to November 2005 , 92 patients with cervical cancer stage IA2 to IIA were r and omly assigned for surgical treatment with conventional radical hysterectomy ( CRH ) or NSRH , and 86 patients finally included in the analysis . Adequacy of nerve sparing , radicality , bladder function , and oncologic safety were assessed by quantifying the nerve fibers in the paracervix , measuring the extent of paracervix and harvested lymph nodes ( LNs ) , urodynamic study ( UDS ) with International Prostate Symptom Score ( IPSS ) , and 10-year disease-free survival ( DFS ) , respectively . Results There were no differences in clinicopathologic characteristics between two groups . The median number of nerve fiber was 12 ( range , 6 to 21 ) and 30 ( range , 17 to 45 ) in the NSRH and CRH , respectively ( p<0.001 ) . The extent of resected paracervix and number of LNs were not different between the two groups . Volume of residual urine and bladder compliance were significantly deteriorated at 12 months after CRH . On the contrary , all parameters of UDS were recovered no later than 3 months after NSRH . Evaluation of the IPSS showed that the frequency of long-term urinary symptom was higher in CRH than in the NSRH group . The median duration before the postvoid residual urine volume became less than 50 mL was 11 days ( range , 7 to 26 days ) in NSRH group and was 18 days ( range , 10 to 85 days ) in CRH group ( p<0.001 ) . No significant difference was observed in the 10-year DFS between two groups . Conclusion NSRH appears to be effective in preserving bladder function without sacrificing oncologic safety OBJECTIVE Surgical therapy for cervical carcinoma carries a significant risk of functional impairment to the bladder . This study evaluates the feasibility and complications of nerve-sparing radical hysterectomy ( NRH ) in Taiwan . METHODS Between March 2010 and March 2011 , consecutive patients diagnosed with early stage cervical cancer ( FIGO stage Ia2 to Ib1 ) and tumor size < 3 cm were recruited prospect ively to undergo NRH or conventional radical hysterectomy ( RH ) . Patients with histories of urinary stress incontinence or bladder dysfunction disease were excluded . A modified Tokyo nerve-sparing radical hysterectomy was performed . RESULTS A total of 30 patients were enrolled . Among these , 18 patients underwent NRH with successful bilaterally nerve-sparing procedures in 15 cases ( 83 % ) , unilaterally nerve-sparing procedures in 2 cases ( 11 % ) , and a failure in 1 case ( 6 % ) . The indwelling catheter was removed on postoperative day 6 . The mean±SD duration from operation to spontaneous voiding was 6.8 ± 1.5 days for women who underwent NRH ; the corresponding duration for women who underwent RH or failed NRH was 20.6 ± 3 days . None of the patients who underwent NRH required intermittent catheterization . All 12 patients who underwent RH needed self-catheterization after discharge . There was a significant reduction in the incidence of postoperative self-catheterization ( p<0.01 ) and bladder dysfunction ( p<0.006 ) . Average satisfaction score analyzed by the Likert-scale question naire was 4.5 for the NRH group and 1.9 for RH group ( p<0.0001 ) . CONCLUSIONS We concluded that the new technique of NRH can reduce postoperative bladder dysfunctions OBJECTIVE To assess the nerve-sparing radical hysterectomy ( NSRH ) technique and its impact on postoperative voiding function . METHODS Forty-four patients with International Federation of Gynecology and Obstetrics ( FIGO ) stage I b1-IIa cervical cancer were enrolled and r and omized into NSRH group ( study group , n = 22 ) and conventional radical hysterectomy ( CRH ) group ( control group , n = 22 ) . The pelvic autonomic nerve pathway ( including hypogastric nerve , pelvic splanchnic nerve , inferior hypogastric plexus and bladder branch ) was completely preserved in the NSRH group . Related parameters were compared between the two groups . RESULTS The estimated blood loss in NSRH group and CRH group were ( 550 + /- 241 ) ml and ( 475 + /- 284 ) ml , respectively , with no significant difference ( P > 0.05 ) . The mean operation time in NSRH group and CRH group were ( 329 + /- 43 ) min and ( 272 + /- 56 ) min , respectively , with a significant difference ( P < 0.01 ) . More patients in NSRH group had post-void residual urine volume ( PVR ) < 100 ml than that in CRH group on day 8 after surgery ( 68 % vs. 18 % , P < 0.01 ) . The median duration of postoperative catheterization was significantly shorter in NRSH group ( 8 - 23 days , median 8 days ) than that in CRH group ( 8 - 32 days , median 20 days ; P < 0.01 ) . Neither surgery-related injury nor pathologically positive margin was reported in either of the groups . CONCLUSIONS NSRH is a feasible and safe technique for preserving bladder function . Larger prospect i ve studies are needed to confirm the efficacy of this technique OBJECTIVE To decrease postoperative morbidity associated with radical hysterectomy Rutledge type III , we identified the parasympathetic innervation of the bladder in the cardinal ligament . METHODS During laparoscopic dissection of the cardinal ligament , we used 7x magnification on 38 consecutive patients with cervical cancer stages IB1 to IIIA with high risk for parametrial involvement when we performed laparoscopy-assisted radical vaginal hysterectomy type III between August 1997 and January 1999 . RESULTS The middle rectal artery was identified as a l and mark separating the vascular from the neural part of the cardinal ligament . The neural part was shown to contain the splanchnic pelvic nerves which anastomose with the pelvic plexus . Following preservation of these neural structures all patients were able to void their bladder spontaneously . Following nerve-sparing technique , patients regained bladder function significantly quicker compared with a control group ( n = 28 ) in which the neural part of the cardinal ligament had not been preserved : suprapubic drainage 11.2 days versus 21.4 days ( P = 0.0007 ) . CONCLUSION Using the middle rectal artery as a l and mark the neural part of the cardinal ligament can be preserved , result ing in preservation of the motor function of the bladder Objective : To investigate the bladder function recovery and quality of life ( QOL ) using nerve-sparing radical hysterectomy ( NSRH ) in treating early invasive cervical carcinoma . Methods : Subjects included patients who underwent radical hysterectomy by laparotomy for early-stage cervical carcinoma . Thirty-one patients were r and omly assigned to 2 groups : group A , 15 patients who underwent NSRH ; and group B , 16 patients who underwent classical radical hysterectomy . We observed the patients ' general clinical information , surgical characteristics , postoperative vital signs , pathological findings , adjuvant therapies , and adverse effects . A urodynamic study was used to assess the bladder function . The patients ' QOL was evaluated by Functional Assessment of Cervical Cancer Therapy ( FACT-Cx ) . Results : Twenty-nine patients completed the study . No significant differences were found in age , body mass index , surgery characteristics , pathological findings , adjuvant therapies , and main adverse effects between the 2 groups ( P > 0.05 ) . The postoperative time of bladder function recovery in group A was obviously earlier than that in group B ( P < 0.05 ) . The urodynamic study showed that the extent of bladder function recovery in group A was better than that in group B ( P < 0.05 ) . The QOL in group A evaluated 1 year after operation was improved compared with that in group B ( P < 0.05 ) . The QOL analysis showed that group A did much better than group B in social and family life , emotional well-being , working status , and the symptom correlated with the operation ( P < 0.05 ) . No significant differences were found in basic bodily functions ( P > 0.05 ) . Conclusions : Nerve-sparing radical hysterectomy is a safe and reliable technique for early invasive cervical carcinoma . The postoperative bladder function recovery and the patients ' QOL were improved after NSRH compared with the control group . Therefore , NSRH could be an alternative management to modify the classical surgery for cervical carcinoma with International Federation of Gynecology and Obstetrics stages IB1 to IIA We performed unilateral or bilateral nerve-sparing ( UNS or BNS ) radical hysterectomies combined with a parametrial excision in patients with locally advanced cervical cancer . The parametrial excision technique is characterized by a meticulous sharp dissection of the avascular plane outside the visceral fascia of the uterus and vagina under direct vision , providing an en bloc parametria and ensuring that all regional spread of the disease is contained within negative surgical margins . The aim of this study was to describe this surgical technique and to retrospectively evaluate the feasibility and the impact on early bladder function . From February 2005 to November 2006 , 32 patients with FIGO stage IB – IIB cervical cancer , who had the tumor of more than 20 mm in diameter , underwent the UNS surgery or BNS surgery . A parametrial excision was performed in all the patients . The surgical procedure was safely completed in all the patients . Though 14 patients had tumor invasion to the parametria , none of the patients had a positive surgical margin in the parametrium . The bladder function of patients in the UNS group immediately after surgery was more damaged than that in the BNS group . However , all the patients in both groups recovered spontaneous voiding with no need of self-catheterization during the perioperative periods . This preliminary study showed that the surgical technique is feasible and safe . For confirmation of the efficacy of this technique , further large prospect i ve studies are needed The objective of this study was to assess the postsurgical bladder function by urodynamic study in patients with cervical cancer treated with nerve-sparing radical hysterectomy . A total of 27 consecutive patients were included in the study . Of the 27 patients , autonomic nerves had been completely preserved at least on one side in 22 patients ( group A ) , and autonomic nerves could not be successfully preserved in five patients ( group B ) . In group A , there was no significant difference in compliance at the moment of strong desire to void , maximum flow rate , and residual urine volume between before the operation and at 12 months after the operation . However , abdominal pressure at maximum flow had significantly increased in patients of group B than of group A. Detrusor contraction pressure at maximum flow had significantly decreased in patients of group B than of group A. Bladder sensation was diminished in three cases ( 60 % ) of group B but preserved in all the patients of group A. Although it is still preliminary , our surgical technique described in this report is thought to be effective for preservation of bladder function . For further evaluation of the efficacy of nerve-sparing radical hysterectomy in terms of quality of life and survival of patients , a prospect i ve r and omized trial needs to be performed |
13,801 | 31,357,986 | In addition , it developed students ’ learning enthusiasm , students ’ self- study ability , thinking ability , and enhanced students ’ communication skills .
The results indicated that such novel pedagogy is compatible with the present situation of Chinese pharmacy education .
And it could be considered as an effective method to enhance both the theoretical test scores and various abilities of Chinese pharmacy students | Background Recent years have witnessed the wide application of team-based learning(TBL ) pedagogy in Chinese pharmacy education .
However , the relevant systematic review evaluating the effects of such new pedagogical approach has not been established .
The present study was design ed to examine systematic ally the effect of using TBL approach in pharmacy education in China . | 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 |
13,802 | 31,607,465 | Incidence often peaked earlier ( during teenage years ) among high-risk groups compared with general population s. Since 2005 , HIV incidence among adolescent girls and young women declined in Rakai ( Ug and a ) and Manical and ( Zimbabwe ) , and also declined among female sex workers in Kenya , but not in the highest-risk communities in South Africa and Ug and a. INTERPRETATION Few sources of direct estimates of HIV incidence exist in high-burden countries and trend analyses with disaggregated data for age and sex are rare but indicate recent declines among adolescent girls and young women .
In some of the highest-risk setting s , however , little evidence exists to suggest ART availability and other efforts slowed transmission by 2016 .
Despite wide geographical diversity in absolute levels of incidence in adolescent girls and young women , risk relative to males persisted in all setting s , with the greatest sex differentials in the youngest age groups . | BACKGROUND The roll-out of antiretroviral therapy ( ART ) has changed context s of HIV risk , but the influence on HIV incidence among young women is not clear .
We aim ed to summarise direct estimates of HIV incidence among adolescent girls and young women since ART and before large investments in targeted prevention for those in sub-Saharan Africa . | BACKGROUND Female-initiated HIV-prevention options , such as microbicides , are urgently needed . We assessed Carraguard , a carrageenan-based compound developed by the Population Council , for its efficacy and long-term safety in prevention of HIV infection in women . METHODS We undertook a r and omised , placebo-controlled , double-blind trial in three South African sites in sexually-active , HIV-negative women , aged 16 years and older . 6202 participants , who were r and omly assigned by a block r and omisation scheme to Carraguard ( n=3103 ) or placebo ( methylcellulose [ n=3099 ] ) , were instructed to use one applicator of gel plus a condom during each vaginal sex act . Participants were followed up for up to 2 years . Visits every 3 months included testing for HIV presence and pregnancy , pelvic examinations , risk reduction counselling , and treatment for curable sexually transmitted infections and symptomatic vaginal infections . The primary outcome was time to HIV seroconversion . Analysis was in the efficacy population ( a subset of the intention-to-treat population , excluding participants for whom efficacy could not be assessed ) . This study is registered with Clinical Trials.gov , number NCT00213083 . FINDINGS For the primary outcome ( time to HIV seroconversion ) we analysed 3011 women in the Carraguard group and 2994 in the placebo group . HIV incidence was 3.3 per 100 woman-years ( 95 % CI 2.8 - 3.9 ) in the Carraguard group ( 134 events ) and 3.8 per 100 woman-years ( 95 % CI 3.2 - 4.4 ) in the placebo group ( 151 events ) , with no significant difference in the distribution of time to seroconversion ( p=0.30 ) . The covariate-adjusted hazard ratio was 0.87 ( 95 % CI 0.69 - 1.09 ) . Rates of self-reported gel use ( 96.2 % Carraguard , 95.9 % placebo ) and condom use ( 64.1 % in both groups ) at last sex acts were similar in both groups . On the basis of applicator testing , however , gel was estimated to have been used in only 42.1 % of sex acts , on average ( 41.1 % Carraguard , 43.1 % placebo ) . 1420 ( 23 % ) women in the intention-to-treat population had adverse events ( 713 Carraguard , 707 placebo ) , and 95 ( 2 % ) women had adverse events that were related to gel use ( 48 Carraguard , 47 placebo ) . Serious adverse events occurred in 72 ( 2 % ) women in the Carraguard group and 78 ( 3 % ) in the placebo group , only one of which was considered possibly related to gel use ( placebo group ) . INTERPRETATION This study did not show Carraguard 's efficacy in prevention of vaginal transmission of HIV . No safety concerns were recorded Purpose The Manical and cohort was established to provide robust scientific data on HIV prevalence and incidence , patterns of sexual risk behaviour and the demographic impact of HIV in a sub-Saharan African population subject to a generalised HIV epidemic . The aims were later broadened to include provision of data on the coverage and effectiveness of national HIV control programmes including antiretroviral therapy ( ART ) . Participants General population open cohort located in 12 sites in Manical and , east Zimbabwe , representing 4 major socioeconomic strata ( small towns , agricultural estates , roadside settlements and subsistence farming areas ) . 9,109 of 11,453 ( 79.5 % ) eligible adults ( men 17 - 54 years ; women 15–44 years ) were recruited in a phased household census between July 1998 and January 2000 . Five rounds of follow-up of the prospect i ve household census and the open cohort were conducted at 2-year or 3-year intervals between July 2001 and November 2013 . Follow-up rates among surviving residents ranged between 77.0 % ( over 3 years ) and 96.4 % ( 2 years ) . Findings to date HIV prevalence was 25.1 % at baseline and had a substantial demographic impact with 10-fold higher mortality in HIV-infected adults than in uninfected adults and a reduction in the growth rate in the worst affected areas ( towns ) from 2.9 % to 1.0%pa . HIV infection rates have been highest in young adults with earlier commencement of sexual activity and in those with older sexual partners and larger numbers of lifetime partners . HIV prevalence has since fallen to 15.8 % and HIV incidence has also declined from 2.1 % ( 1998 - 2003 ) to 0.63 % ( 2009 - 2013 ) largely due to reduced sexual risk behaviour . HIV-associated mortality fell substantially after 2009 with increased availability of ART . Future plans We plan to extend the cohort to measure the effects on the epidemic of current and future HIV prevention and treatment programmes . Proposals for access to these data and for collaboration are welcome BACKGROUND Universal antiretroviral therapy ( ART ) , as per the 2015 WHO recommendations , might reduce population HIV incidence . We investigated the effect of universal test and treat on HIV acquisition at population level in a high prevalence rural region of South Africa . METHODS We did a phase 4 , open-label , cluster r and omised trial of 22 communities in rural KwaZulu-Natal , South Africa . We included individuals residing in the communities who were aged 16 years or older . The clusters were composed of aggregated local areas ( neighbourhoods ) that had been identified in a previous study in the Hlabisa subdistrict . The study statisticians r and omly assigned clusters ( 1:1 ) with MapInfo Pro ( version 11.0 ) to either the control or intervention communities , stratified on the basis of antenatal HIV prevalence . We offered residents repeated rapid HIV testing during home-based visits every 6 months for about 4 years in four clusters , 3 years in six clusters , and 2 years in 12 clusters ( 58 cluster-years ) and referred HIV-positive participants to trial clinics for ART ( fixed-dose combination of tenofovir , emtricitabine , and efavirenz ) regardless of CD4 cell count ( intervention ) or according to national guidelines ( initially ≤350 cells per μL and < 500 cells per μL from January , 2015 ; control ) . Participants and investigators were not masked to treatment allocation . We used dried blood spots once every 6 months provided by participants who were HIV negative at baseline to estimate the primary outcome of HIV incidence with cluster-adjusted Poisson generalised estimated equations in the intention-to-treat population after 58 cluster-years of follow-up . This study is registered with Clinical Trials.gov , number NCT01509508 , and the South African National Clinical Trials Register , number DOH-27 - 0512 - 3974 . FINDINGS Between March 9 , 2012 , and June 30 , 2016 , we contacted 26 518 ( 93 % ) of 28 419 eligible individuals . Of 17 808 ( 67 % ) individuals with a first negative dried blood spot test , 14 223 ( 80 % ) had subsequent dried blood spot tests , of whom 503 seroconverted after follow-up of 22 891 person-years . Estimated HIV incidence was 2·11 per 100 person-years ( 95 % CI 1·84 - 2·39 ) in the intervention group and 2·27 per 100 person-years ( 2·00 - 2·54 ) in the control group ( adjusted hazard ratio 1·01 , 95 % CI 0·87 - 1·17 ; p=0·89 ) . We documented one case of suicidal attempt in a woman following HIV seroconversion . 128 patients on ART had 189 life-threatening or grade 4 clinical events : 69 ( 4 % ) of 1652 in the control group and 59 ( 4 % ) of 1367 in the intervention group ( p=0·83 ) . INTERPRETATION The absence of a lowering of HIV incidence in universal test and treat clusters most likely result ed from poor linkage to care . Policy change to HIV universal test and treat without innovation to improve health access is unlikely to reduce HIV incidence . FUNDING ANRS , GiZ , and 3ie BACKGROUND Preexposure prophylaxis with antiretroviral drugs has been effective in the prevention of human immunodeficiency virus ( HIV ) infection in some trials but not in others . METHODS In this r and omized , double-blind , placebo-controlled trial , we assigned 2120 HIV-negative women in Kenya , South Africa , and Tanzania to receive either a combination of tenofovir disoproxil fumarate and emtricitabine ( TDF-FTC ) or placebo once daily . The primary objective was to assess the effectiveness of TDF-FTC in preventing HIV acquisition and to evaluate safety . RESULTS HIV infections occurred in 33 women in the TDF-FTC group ( incidence rate , 4.7 per 100 person-years ) and in 35 in the placebo group ( incidence rate , 5.0 per 100 person-years ) , for an estimated hazard ratio in the TDF-FTC group of 0.94 ( 95 % confidence interval , 0.59 to 1.52 ; P=0.81 ) . The proportions of women with nausea , vomiting , or elevated alanine aminotransferase levels were significantly higher in the TDF-FTC group ( P=0.04 , P<0.001 , and P=0.03 , respectively ) . Rates of drug discontinuation because of hepatic or renal abnormalities were higher in the TDF-FTC group ( 4.7 % ) than in the placebo group ( 3.0 % , P=0.051 ) . Less than 40 % of the HIV-uninfected women in the TDF-FTC group had evidence of recent pill use at visits that were matched to the HIV-infection window for women with seroconversion . The study was stopped early , on April 18 , 2011 , because of lack of efficacy . CONCLUSIONS Prophylaxis with TDF-FTC did not significantly reduce the rate of HIV infection and was associated with increased rates of side effects , as compared with placebo . Despite substantial counseling efforts , drug adherence appeared to be low . ( Supported by the U.S. Agency for International Development and others ; FEM-PrEP Clinical Trials.gov number , NCT00625404 . ) Introduction Prevention of acute HIV infections in pregnancy is required to achieve elimination of pediatric HIV . Identification and support for HIV negative pregnant women and their partners , particularly serodiscordant couples , are critical . A mixed method study done in Southern Mozambique estimated HIV incidence during pregnancy , associated risk factors and factors influencing partner 's HIV testing . Methods Between April 2008 and November 2011 , a prospect i ve cohort of 1230 HIV negative pregnant women was followed during pregnancy . A structured question naire , HIV testing , and collection of dried blood spots were done at 2–3 scheduled visits . HIV incidence rates were calculated by repeat HIV testing and risk factors assessed by Poisson regression . A qualitative study including 37 individual interviews with men , women , and nurses and 11 focus group discussion s ( n = 94 ) with men , women and gr and mothers explored motivators and barriers to uptake of male HIV testing . Results HIV incidence rate was estimated at 4.28/100 women-years ( 95%CI : 2.33–7.16 ) . Significant risk factors for HIV acquisition were early sexual debut ( RR 3.79 , 95%CI : 1.04–13.78 , p = 0.04 ) and living in Maputo Province ( RR 4.35 , 95%CI : 0.97–19.45 , p = 0.05 ) . Nineteen percent of women reported that their partner had tested for HIV ( 93 % knew the result with 8/213 indicating an HIV positive partner ) , 56 % said their partner had not tested and 19 % did not know their partner test status . Of the 14 seroconversions , only one reported being in a serodiscordant relationship . Fear of discrimination or stigma was reported as a key barrier to male HIV testing , while knowing the importance of getting tested and receiving care was the main motivator . Conclusions HIV incidence during pregnancy is high in Southern Mozambique , but knowledge of partners ' HIV status remains low . Knowledge of both partners ' HIV status is critical for maximal effectiveness of prevention and treatment services to reach elimination of pediatric HIV/AIDS Background The study aim ed to assess the feasibility of conducting large scale HIV prevention clinical trials in Mozambique by measuring HIV prevalence and incidence among women of reproductive age . This paper describes the baseline socio-demographic characteristics of the Mozambique Microbicides Development Programme ( MDP ) feasibility cohort , baseline prevalence of HIV and other STIs , and HIV incidence . Methods The Mozambique MDP feasibility study was conducted from September 2007 to August 2009 in urban Mavalane and rural Manhiça , in Southern Mozambique . Sexually active , HIV negative women aged 18 years and above were recruited to attend the study clinic every 4 weeks for a total of 40 weeks . At baseline , we collected demographic and sexual behaviour data , sample s to test for sexually transmitted infections ( STI ) and conducted HIV rapid testing . STI and HIV testing were repeated at clinical follow-up visits . We describe HIV prevalence of women at screening , the demographic , behavioural and clinical characteristics of women at enrolment , and HIV incidence during follow-up . Results We screened 793 women ( 369 at Mavalane and 424 at Manhiça ) and enrolled 505 eligible women ( 254 at Mavalane and 251 at Manhiça ) . Overall HIV prevalence at screening was 17 % ; 10 % at Mavalane and 22 % at Manhiça . Women screened at Manhiça were twice as likely as women screened at Mavalane to be HIV positive and HIV positive status was associated with younger age ( 18–34 ) , lower educational level , not using a reliable method of contraception and being Zionist compared to other Christian religions . At enrolment contraceptive use was low in both clinics at 19 % in Mavalane and 21 % in Manhiça , as was reported condom use at last sex act at 48 % in Mavalane and 25 % in Manhiça . At enrolment , 8 % of women tested positive for Trichomonas vaginalis , 2 % for Neisseria gonorrhoeae , 4 % for Chlamydia trachomatis and 46 % for bacterial vaginosis . In Manhiça , 8 % of women had active syphilis at screening . HIV incidence was 4.3 per 100 person years at Mavalane and 9.2 per 100 person years at Manhiça . Conclusions We demonstrated the ability to recruit a cohort of women at risk of HIV who were willing to participate in clinical research . The high HIV incidence necessitates additional action around HIV prevention for women and offers opportunities to evaluate the impact of available prevention options , such as treatment as prevention and oral PrEP . The high HIV incidence and STI prevalence also offers opportunities to evaluate the added benefit of potential prevention options such as new formulations of oral PrEP , vaginal microbicides ( also called topical PrEP ) , vaccines , and multi- purpose technologies for HIV , STIs and contraception Summary Background Studies of HIV-serodiscordant couples in stable sexual relationships have provided convincing evidence that antiretroviral therapy can prevent the transmission of HIV . We aim ed to quantify the preventive effect of a public-sector HIV treatment and care programme based in a community with poor knowledge and disclosure of HIV status , frequent migration , late marriage , and multiple partnerships . Specifically , we assessed whether an individual 's hazard of HIV acquisition was associated with antiretroviral therapy coverage among household members of the opposite sex . Methods In this prospect i ve cohort study , we linked patients ' records from a public-sector HIV treatment programme in rural KwaZulu-Natal , South Africa , with population -based HIV surveillance data collected between 2004 and 2012 . We used information about coresidence to construct estimates of HIV prevalence and antiretroviral therapy coverage for each household . We then regressed the time to HIV seroconversion for 14 505 individuals , who were HIV-uninfected at baseline and individually followed up over time regarding their HIV status , on opposite-sex household antiretroviral therapy coverage , controlling for household HIV prevalence and a range of other potential confounders . Findings 2037 individual HIV seroconversions were recorded during 54 845 person-years of follow-up . For each increase of ten percentage points in opposite-sex household antiretroviral therapy coverage , the HIV acquisition hazard was reduced by 6 % ( 95 % CI 2–9 ) , after controlling for other factors . This effect size translates into large reductions in HIV acquisition hazards when household antiretroviral therapy coverage is substantially increased . For example , an increase of 50 percentage points in household antiretroviral therapy coverage ( eg , from 20 % to 70 % ) reduced the hazard of HIV acquisition by 26 % ( 95 % CI 9–39 ) . Interpretation Our findings provide further evidence that antiretroviral therapy significantly reduces the risk of onward transmission of HIV in a real-world setting in sub-Saharan Africa . Awareness that antiretroviral therapy can prevent transmission to coresident sexual partners could be a powerful motivator for HIV testing and antiretroviral treatment uptake , retention , and adherence . Funding Wellcome Trust and National Institute of Child Health and Human Development ( US National Institutes of Health ) Background An effective HIV vaccine is still elusive . Of the 9 HIV preventive vaccine efficacy trials conducted to- date , only one reported positive results of modest efficacy . More efficacy trials need to be conducted before one or more vaccines are eventually licensed . We assessed the suitability of fishing communities in Ug and a for future HIV vaccine efficacy trials . Methods A community-based cohort study was conducted among a r and om sample of 2191 participants aged 18–49 years . Data were collected on socio-demographic characteristics , HIV risky behaviors , and willingness to participate in future HIV vaccine trials ( WTP ) . Venous blood was collected for HIV serological testing . Retention/follow rates and HIV incidence rates per 100 person years at-risk ( pyar ) were estimated . Adjusted prevalence proportion ratios ( PPRs ) of retention and odds ratios ( ORs ) of lack of WTP were estimated using log-binomial and logistic regression models respectively . Results Overall retention rate was 76.9 % ( 1685/2191 ) , highest ( 89 % ) among participants who had spent 5 + years in the community and lowest ( 54.1 % ) among those with < 1 year stay . Significant predictors of retention included tribe/ethnicity , baseline HIV negative status , and longer than 1 year stay in the community . Overall WTP was 89.1 % ( 1953/2191 ) . Lack of WTP was significantly higher among women than men [ adj . OR = 1.51 ( 95 % CI , 1.14- 2.00 ) ] and among participants who had stayed in fishing communities for 10 or more years relative to those with less than one year [ adj . OR = 1.78 ( 95 % CI , 1.11 - 2.88 ) ] . Overall HIV incidence rate per 100 pyar was 3.39 ( 95 % CI ; 2.55 - 4.49 ) . Participants aged 25–29 years had highest incidence rates ( 4.61 - 7.67/100 pyar ) and high retention rates between 78.5 and 83.1 % . In a combined analysis of retention and incidence rates participants aged 30 + years had retention rates ~80 % but low incidence rates ( 2.45 - 3.57 per 100 pyar ) while those aged 25–29 years had the highest incidence rates ( 4.61 - 7.67/100 pyar ) and retention rates 78.5 - 83.1 % . Conclusions There is high HIV incidence , retention and WTP among fishing communities around L. Victoria , Ug and a which make these communities appropriate for future HIV prevention efficacy studies including vaccine trials Objectives : A r and omized , double-blind , placebo-controlled trial ( RCT ) of herpes simplex virus type 2 suppressive therapy with acyclovir 400 mg twice daily conducted among women in northwestern Tanzania reported a similar rate of HIV acquisition in both trial arms ( Current Controlled Trials number IS RCT N35385041 ) . Risk factors for HIV incidence were examined in the context of 3-monthly follow-up visits offering both voluntary counselling and testing and care for sexually transmitted infections . Design : Prospect i ve cohort analysis of trial participants enrolled and followed for up to 30 months . Methods : Risk factors for HIV acquisition were analysed using Cox regression . Results : Overall , 821 herpes simplex virus type 2 seropositive , HIV seronegative women were r and omized ; 400 r and omized to acyclovir and 421 to placebo ; 659 ( 80.3 % ) completed follow-up . HIV incidence was 4.27 per 100 person-years . There was no overall impact of acyclovir on HIV incidence [ hazard ratio = 1.01 ; 95 % confidence interval ( CI ) 0.61–1.66 ] . HIV acquisition was independently associated with younger age at enrolment ( age 16–19 vs. 30–35 : hazard ratio = 4.02 ; 95 % CI 1.67–9.68 ) , alcohol consumption at enrolment ( ≥30 drinks/week vs. none : hazard ratio = 4.39 , 95 % CI 1.70–11.33 ) , having paid sex within the previous 3 months ( hazard ratio = 1.82 , 95 % CI 1.09–3.05 ) , recent infection with gonorrhoea ( hazard ratio = 3.62 , 95 % CI 1.62–8.08 ) and injections in the previous 3 months ( hazard ratio = 3.45 , 95 % CI 1.62–7.34 ) . There was some evidence of an association between HIV incidence and living in the recruitment community for less than 2 years ( hazard ratio = 1.75 , 95 % CI 0.98–3.10 ) and exposure to hormonal contraception ( hazard ratio = 1.60 , 95 % CI 0.93–2.76 ) . Conclusion : A high incidence of HIV was observed in this trial cohort , especially in young women . Interventions are needed to address the risk associated with alcohol use and to sustain control of other sexually transmitted infections BACKGROUND In mature generalized human immunodeficiency virus ( HIV ) epidemics , as survival from accessing antiretroviral treatment ( ART ) increases , HIV prevalence data may be suboptimal and difficult to interpret without HIV incidence rates . OBJECTIVE To determine the HIV incidence rate among rural and urban women in KwaZulu-Natal , South Africa . METHODS We conducted a prospect i ve cohort study from March 2004 to May 2007 . Volunteers were recruited from a rural family-planning clinic and an urban clinic for sexually transmitted infections . Consenting , HIV-uninfected women aged 14 - 30 years were enrolled . Demographic , clinical , sexual and behavioural data were collected using st and ardized question naires with HIV risk reduction counselling and HIV testing . Pelvic examinations were completed at quarterly visits . RESULTS The HIV prevalence at screening was 35.7 % [ 95 % confidence interval ( CI ) 32.7 - 38.8 ] amongst rural women and 59.3 % ( 95 % CI 56.5 - 62.0 ) amongst urban women . A total of 594/2240 ( 26.5 % ) enrolled women contributed to 602 person-years ( PYs ) of follow-up . The median age was 22 years [ inter-quartile range 18 - 23 years ] . HIV incidence rate was 6.5/100 PY ( 95 % CI 4.4 - 9.2 ) amongst rural women and 6.4/100 PY ( 95 % CI 2.6 - 13.2 ) amongst urban women . HIV incidence rate of 17.2/100 PY ( 95 % CI 2.1 - 62.2 ) was highest amongst urban women < 20 years of age and 10.2/100 PY ( 95 % CI 4.1 - 20.9 ) amongst rural women ≥ 25 years of age . CONCLUSION HIV incidence rates are devastatingly high in young women in rural and urban KwaZulu-Natal , despite reports of stabilized HIV prevalence observed in current surveillance data . The diffuse nature of the HIV epidemic underscores the urgent need to enhance HIV prevention and treatment modalities OBJECTIVE To estimate the potential impact of using hormonal contraceptives on rates of infection with human immunodeficiency virus type 1 ( HIV-1 ) and pregnancy by theoretically removing the use of hormonal contraceptives from a study population . METHODS A prospect i ve cohort study included 3704 HIV-negative women who were enrolled in two biomedical trials that tested two vaginal microbicides ( PRO 2000 and Carraguard ® ) for the prevention of HIV-1 in Durban , South Africa , in 2004 - 2009 . Cox proportional hazards regression models along with partial population attributable risks ( PARs ) and their 95 % confidence intervals ( CIs ) were calculated to assess the relative population -level impact of the use of hormonal contraceptives on HIV-1 seroconversion rates and on pregnancy rates . FINDINGS Women who reported using hormonal contraceptives at enrolment in the trial had a higher risk of HIV-1 seroconversion ( adjusted hazards ratio : 1.24 ; 95 % CI : 0.97 - 1.58 ) than women who reported using other types of contraceptives at enrolment . At the population level , the use of hormonal contraceptives ( pills or injectables ) at baseline and during study follow-up accounted for approximately 20 % ( 95 % CI : 16 - 22 ) of HIV-1 seroconversions . However , the partial PAR indicated a relative impact of 12 % ( 95 % CI : 9.0 - 15.7 ) . On the other h and , 72 % ( 95 % CI : 66 - 77 ) of the pregnancies could have been avoided if all women had used hormonal contraceptives . CONCLUSION Women using hormonal contraceptives need comprehensive counselling on simultaneous prevention of HIV-1 infection Background HIV is prevalent in Sofala Province , Mozambique . To inform future prevention research , we undertook a study in the provincial capital ( Beira ) to measure HIV incidence in women at higher risk of HIV and assess the feasibility of recruiting and retaining them as research participants . Methods Women age 18–35 were recruited from schools and places where women typically meet potential sexual partners . Eligibility criteria included HIV-seronegative status and self-report of at least 2 sexual partners in the last month . History of injection drug use was an exclusion criterion , but pregnancy was not . Participants were scheduled for monthly follow-up for 12 months , when they underwent face-to-face interviews , HIV counseling and testing , and pregnancy testing . Results 387 women were eligible and contributed follow-up data . Most were from 18–24 years old ( median 21 ) . Around one-third of participants ( 33.8 % ) reported at least one new sexual partner in the last month . Most women ( 65.5 % ) reported not using a modern method of contraception at baseline . Twenty-two women seroconverted for a prospect i ve HIV incidence of 6.5 per 100 woman-years ( WY ; 95 % confidence interval ( CI ) : 4.1–9.9 ) . Factors associated with HIV seroconversion in the multivariable analysis were : number of vaginal sex acts without using condoms with partners besides primary partner in the last 7 days ( hazard ratio ( HR ) 1.7 ; 95 % CI : 1.2–2.5 ) and using a form of contraception at baseline other than hormonal or condoms ( vs. no method ; HR 25.3 ; 95 % CI : 2.5–253.5 ) . The overall retention rate was 80.0 % for the entire follow-up period . Conclusions We found a high HIV incidence in a cohort of young women reporting risky sexual behavior in Beira , Mozambique . HIV prevention programs should be strengthened . Regular HIV testing and condom use should be encouraged , particularly among younger women with multiple sexual partners Objective To assess the impact of Stepping Stones , a HIV prevention programme , on incidence of HIV and herpes simplex type 2 ( HSV-2 ) and sexual behaviour . Design Cluster r and omised controlled trial . Setting 70 villages ( clusters ) in the Eastern Cape province of South Africa . Participants 1360 men and 1416 women aged 15 - 26 years , who were mostly attending schools . Intervention Stepping Stones , a 50 hour programme , aims to improve sexual health by using participatory learning approaches to build knowledge , risk awareness , and communication skills and to stimulate critical reflection . Villages were r and omised to receive either this or a three hour intervention on HIV and safer sex . Interviewers administered question naires at baseline and 12 and 24 months and blood was tested for HIV and HSV-2 . Main outcome measures Primary outcome measure : incidence of HIV . Other outcomes : incidence of HSV-2 , unwanted pregnancy , reported sexual practice s , depression , and substance misuse . Results There was no evidence that Stepping Stones lowered the incidence of HIV ( adjusted incidence rate ratio 0.95 , 95 % confidence interval 0.67 to 1.35 ) . The programme was associated with a reduction of about 33 % in the incidence of HSV-2 ( 0.67 , 0.46 to 0.97 ; P=0.036)—that is , Stepping Stones reduced the number of new HSV-2 infections over a two year period by 34.9 ( 1.6 to 68.2 ) per 1000 people exposed . Stepping Stones significantly improved a number of reported risk behaviours in men , with a lower proportion of men reporting perpetration of intimate partner violence across two years of follow-up and less transactional sex and problem drinking at 12 months . In women desired behaviour changes were not reported and those in the Stepping Stones programme reported more transactional sex at 12 months . Conclusion Stepping Stones did not reduce incidence of HIV but had an impact on several risk factors for HIV — notably , HSV-2 and perpetration of intimate partner violence . Trial Registration Clinical Trials NCT00332878 Background Reliable HIV incidence estimates for Mozambique are limited . We conducted a prospect i ve HIV incidence study as part of a clinical research site development initiative in Chókwè district , Gaza Province , southern Mozambique . Methods Between June 2010 and October 2012 , we recruited women at sites where women at higher risk of HIV infection would likely be found . We enrolled and tested 1,429 sexually active women in the screening phase and 479 uninfected women in the prospect i ve phase . Participants were scheduled for 12 + months follow-up , when they underwent face-to-face interviews , HIV counseling and testing , and pregnancy testing . We observed a total of 373.1 woman-years ( WY ) of follow-up , with mean ( median ) of 9.4 ( 9.7 ) women-months per participant . Results The prevalence of HIV was 29.4 % ( 95 % confidence interval [ CI ] : 27.0–31.8 % ) . In multivariable logistic regression analysis , factors that remained significantly associated with prevalent HIV were : older age ( OR : 0.6 ; 95 % CI : 0.4–0.7 ) , lower educational level ( OR : 0.4 ; 95 % CI : 0.3–0.7 ) , and using hormonal contraception ( OR : 0.6 ; 95 % CI : 0.4–0.7 ) or condoms ( OR : 0.5 ; 95 % CI : 0.3–0.7 ) . We observed an HIV incidence rate of 4.6 per 100 WY ( 95 % CI : 2.7 , 7.3 ) . The HIV incidence was 4.8 per 100 WY ( 95 % CI : 2.5 , 8.3 ) in women aged 18–24 years , 4.5 per 100 WY ( 95 % CI : 1.2 , 11.4 ) in women aged 25–29 years and 3.2 per 100 WY ( 95 % CI : 0.1 , 18.0 ) in the 30–35 years stratum . None of the demographic factors or time-varying behavioral factors examined was significantly associated with incident HIV infection in bivariable analysis at p≤0.10 . Conclusions We found a high HIV incidence among sexually active young women in Chókwè , Mozambique . HIV prevention programs should be strengthened in the area , with more comprehensive reproductive health services , regular HIV testing , condom promotion , and messaging about multiple sexual partners Objectives : To quantify the association between intimate partner violence ( IPV ) and incident HIV infection in women in the Rakai Community Cohort Study between 2000 and 2009 . Design and methods : Data were from the Rakai Community Cohort Study annual surveys between 2000 and 2009 . Longitudinal data analysis was used to estimate the adjusted incidence rate ratio ( IRR ) of incident HIV associated with IPV in sexually active women aged 15–49 years , using a multivariable Poisson regression model with r and om effects . The population attributable fraction was calculated . Putative mediators were assessed using Baron and Kenny 's criteria and the Sobel – Goodman test . Results : Women who had ever experienced IPV had an adjusted IRR of incident HIV infection of 1.55 ( 95 % CI 1.25–1.94 , P = 0.000 ) , compared with women who had never experienced IPV . Risk of HIV infection tended to be greater for longer duration of IPV exposure and for women exposed to more severe and more frequent IPV . The adjusted population attributable fraction of incident HIV attributable to IPV was 22.2 % ( 95 % CI 12.5–30.4 ) . There was no evidence that either condom use or number of sex partners in the past year mediated the relationship between IPV and HIV . Conclusion : IPV is associated with incident HIV infection in a population -based cohort in Ug and a , although the adjusted population attributable fraction is modest . The prevention of IPV should be a public health priority , and could contribute to HIV prevention BACKGROUND Swazil and has the highest national HIV prevalence worldwide . The Swazil and HIV Incidence Measurement Survey ( SHIMS ) provides the first national HIV incidence estimate based on prospect ively observed HIV seroconversions . METHODS A two-stage survey sampling design was used to select a nationally representative sample of men and women aged 18 - 49 years from 14 891 households in 575 enumeration areas in Swazil and , who underwent household-based counselling and rapid HIV testing during 2011 . All individuals aged 18 - 49 years who resided or had slept in the household the night before and were willing to undergo home-based HIV testing , answer demographic and behavioural questions in English or siSwati , and provide written informed consent were eligible for the study . We performed rapid HIV testing and assessed sociodemographic and behavioural characteristics with use of a question naire at baseline and , for HIV-seronegative individuals , 6 months later . We calculated HIV incidence with Poisson regression modelling as events per person-years × 100 , and we assessed covariables as predictors with Cox proportional hazards modelling . Survey weighting was applied and all models used survey sampling methods . FINDINGS Between Dec 10 , 2010 , and June 25 , 2011 , 11 897 HIV-seronegative adults were enrolled in SHIMS and 11 232 ( 94 % ) were re-tested . Of these , 145 HIV seroconversions were observed , result ing in a weighted HIV incidence of 2·4 % ( 95 % CI 2·1 - 2·8 ) . Incidence was nearly twice as high in women ( 3·1 % ; 95 % CI 2·6 - 3·7 ) as in men ( 1·7 % ; 1·3 - 2·1 , p<0·0001 ) . Among men , partner 's HIV-positive status ( adjusted hazard ratio [ aHR ] 2·67 , 1·06 - 6·82 , p=0·040 ) or unknown serostatus ( aHR 4·64 , 2·32 - 9·27 , p<0·0001 ) in the past 6 months predicted HIV seroconversion . Among women , significant predictors included not being married ( aHR 2·90 , 1·44 - 5·84 , p=0·0030 ) , having a spouse who lives elsewhere ( aHR 2·66 , 1·29 - 5·45 , p=0·0078 ) , and having a partner in the past 6 months with unknown HIV status ( aHR 2·87 , 1·44 - 5·84 , p=0·0030 ) . INTERPRETATION Swazil and has the highest national HIV incidence in the world . In high-prevalence countries , population -based incidence measures and programmes that further exp and HIV testing and support disclosure of HIV status are needed . FUNDING President 's Emergency Plan for AIDS Relief ( PEPFAR ) by the Centers for Disease Control and Prevention BACKGROUND Clinical trial participants may differ from the source population due to the dem and s of trial participation and self- selection , inadvertent selection of a lower-risk group , or both . We investigated the HIV risk status of volunteers in a Simulated Vaccine Efficacy Trial ( SiVET ) nested within a prospect i ve observational cohort of fisher folks in South Western Ug and a. METHODS Volunteers aged 18 - 49 years , at high risk for HIV from fishing communities in Masaka district were recruited into an observational cohort and followed quarterly . High risk was defined as a self-report , of at least one of the following in the past three months ; sexually transmitted infections , unprotected sex with > 1 partner or a new sexual partner , use of recreational drugs , weekly alcohol use , and /or frequent travel . Volunteers who had at least three months of follow-up in the observational cohort were consecutively enrolled in SiVET , administered Hepatitis B vaccine at months ( 0 , 1 , 6 ) and followed-up three days post vaccinations to mimic a vaccine trial schedule . HIV incidence over the next 12 months was compared between SiVET and the observational cohort studies . RESULTS Between January 2012 and February 2013 , 575 individuals were enrolled in the observational cohort , of whom 282 were enrolled in SiVET between July 2012 and February 2013 . Despite similar pattern of reported risk behaviour in both studies , HIV incidence was higher in observational cohort , 11.4 cases/100 PYO [ 95 % CI : 7.4 - 17.7 ] compared to 3.8 [ 95 % CI : 2.0 - 7.0 ] in SiVET ( p<0.01 ) . SiVET volunteers tended to be men , having some education and longer-term residents , all factors that are also associated with lower HIV risk . CONCLUSION We observed a lower HIV incidence in SiVET than in the observational cohort . The two population s differed significantly in demographics but not in reported risk . HIV incidence estimates from observational cohorts must be used with caution to estimate the trial study size BACKGROUND The use of injectable progestin-only contraceptives has been associated with increased risk of HIV acquisition in observational studies , but the biological mechanisms of this risk remain poorly understood . We aim ed to assess the effects of progestins on HIV acquisition risk and the immune environment in the female genital tract . METHODS In this prospect i ve cohort , we enrolled HIV-negative South African women aged 18 - 23 years who were not pregnant and were living in Umlazi , South Africa from the Females Rising through Education , Support , and Health ( FRESH ) study . We tested for HIV-1 twice per week to monitor incident infection . Every 3 months , we collected demographic and behavioural data in addition to blood and cervical sample s. The study objective was to characterise host immune determinants of HIV acquisition risk , including those associated with injectable progestin-only contraceptive use . Hazard ratios ( HRs ) were estimated using Cox proportional hazards methods . FINDINGS Between Nov 19 , 2012 , and May 31 , 2015 , we characterised 432 HIV-uninfected South African women from the FRESH study . In this cohort , 152 women used injectable progestin-only contraceptives , 43 used other forms of contraception , and 222 women used no method of long-term contraception . Women using injectable progestin-only contraceptives were at substantially higher risk of acquiring HIV ( 12·06 per 100 person-years , 95 % CI 6·41 - 20·63 ) than women using no long-term contraception ( 3·71 per 100 person-years , 1·36 - 8·07 ; adjusted hazard ratio [ aHR ] 2·93 , 95 % CI 1·09 - 7·868 , p=0·0326 ) . HIV-negative injectable progestin-only contraceptive users had 3·92 times the frequency of cervical HIV target cells ( CCR5 + CD4 T cells ) compared with women using no long-term contraceptive ( p=0·0241 ) . Women using no long-term contraceptive in the luteal phase of the menstrual cycle also had a 3·25 times higher frequency of cervical target cells compared with those in the follicular phase ( p=0·0488 ) , suggesting that a naturally high progestin state had similar immunological effects to injectable progestin-only contraceptives . INTERPRETATION Injectable progestin-only contraceptive use and high endogenous progesterone are both associated with increased frequency of activated HIV targets cells at the cervix , the site of initial HIV entry in most women , providing a possible biological mechanism underlying increased HIV acquisition in women with high progestin exposure . FUNDING The Bill and Melinda Gates Foundation and the National Institute of Allergy and Infectious Diseases Background : To control the global HIV epidemic , targeted interventions to reduce the incidence of HIV infections are urgently needed until an effective HIV vaccine is available . This study describes HIV-1 incidence and associated risk factors in a general population cohort of adults from Mbeya region , Tanzania , who participated in a vaccine preparedness study . Methods : We conducted a closed prospect i ve cohort study with 6-monthly follow-up from 2002 to 2006 enrolling adults from the general population . HIV-1 incidence and risk factors for HIV-1 acquisition were analyzed using Cox regression . Results : We observed 2578 seronegative participants for a mean period of 3.06 person years ( PY ) ( 7471 PY in total ) . Overall HIV-1 incidence was 1.35 per 100 PY ( 95 % confidence interval [ CI ] , 1.10 - 1.64/100 PY ) . The highest overall HIV-1 incidence was found in females from Itende village ( 1.55 per 100 PY ; 95 % CI , 0.99 - 2.30/100 PY ) ; the highest age-specific incidence was observed in semiurban males aged 30 to 34 years ( 2.75 per 100 PY ; 95 % CI , 0.75 - 7.04 ) . HIV-1 acquisition was independently associated with female gender ( hazard ratio [ HR ] , 1.64 ; 95 % CI , 1.05 - 2.57 ) , younger age at enrollment ( age 18 - 19 versus 35 - 39 years : HR , 0.29 ; 95 % CI , 0.11 - 0.75 ) , alcohol consumption ( almost daily versus none : HR , 2.01 ; 95 % CI , 1.00 - 4.07 ) , education level ( secondary school versus none : HR , 0.39 ; 95 % CI , 0.17 - 0.89 ) , and number of lifetime sex partners ( more than five versus one : HR , 2.22 ; 95 % CI , 1.13 - 4.36 ) . Conclusions : A high incidence of HIV was observed in this cohort , and incident infection was strongly associated with young age , alcohol consumption , low school education level , and number of sex partners . Targeted interventions are needed to address the elevated risk associated with these factors BACKGROUND Female-controlled methods of HIV prevention are urgently needed . We assessed the effect of provision of latex diaphragm , lubricant gel , and condoms ( intervention ) , compared with condoms alone ( control ) on HIV seroincidence in women in South Africa and Zimbabwe . METHODS We did an open-label , r and omised controlled trial in HIV-negative , sexually active women recruited from clinics and community-based organisations , who were followed up quarterly for 12 - 24 months ( median 21 months ) . All participants received an HIV prevention package consisting of pre-test and post-test counselling about HIV and sexually transmitted infections , testing , treatment of curable sexually transmitted infections , and intensive risk-reduction counselling . The primary outcome was incident HIV infection . This study is registered with Clinical Trials.gov , number NCT00121459 . FINDINGS Overall HIV incidence was 4.0 % per 100 woman-years : 4.1 % in the intervention group ( n=2472 ) and 3.9 % in the control group ( n=2476 ) , corresponding to a relative hazard of 1.05 ( 95 % CI 0.84 - 1.32 , intention-to-treat analysis ) . The proportion of women using condoms was significantly lower in the intervention than in the control group ( 54%vs 85 % of visits , p<0.0001 ) . The proportions of participants who reported adverse events ( 60 % [ 1523 ] vs 61 % [ 1529 ] ) and serious adverse events ( 5 % [ 130 ] vs 4 % [ 101 ] ) were similar between the two groups . INTERPRETATION We observed no added protective benefit against HIV infection when the diaphragm and lubricant gel were provided in addition to condoms and a comprehensive HIV prevention package . Our observation that lower condom use in women provided with diaphragms did not result in increased infection merits further research . Although the intervention seemed safe , our findings do not support addition of the diaphragm to current HIV prevention strategies Objective : To test the hypothesis that increasing community antiretroviral therapy ( ART ) coverage would be associated with lower HIV incidence in female sex workers ( FSWs ) in Mombasa District , Kenya . Design : Prospect i ve cohort study . Methods : From 1998 to 2012 , HIV-negative FSWs were asked to return monthly for an interview regarding risk behavior and testing for sexually transmitted infections including HIV . We evaluated the association between community ART coverage and FSW 's risk of becoming HIV infected using Cox proportional hazards models adjusted for potential confounding factors . Results : One thous and , four hundred and four FSWs contributed 4335 woman-years of follow-up , with 145 acquiring HIV infection ( incidence 3.35/100 woman-years ) . The ART rollout began in 2003 . By 2012 , an estimated 52 % of HIV-positive individuals were receiving treatment . Community ART coverage was inversely associated with HIV incidence ( adjusted hazard ratio 0.77 ; 95 % confidence interval 0.61–0.98 ; P = 0.03 ) , suggesting that each 10 % increase in coverage was associated with a 23 % reduction in FSWs ’ risk of HIV acquisition . Community ART coverage had no impact on herpes simplex virus type-2 incidence ( adjusted hazard ratio 0.97 ; 95 % confidence interval 0.79–1.20 ; P = 0.8 ) . Conclusion : Increasing general population ART coverage was associated with lower HIV incidence in FSWs . The association with HIV incidence , but not herpes simplex virus type-2 incidence , suggests that the effect of community ART coverage may be specific to HIV . Interventions such as preexposure prophylaxis and antiretroviral-containing microbicides have produced disappointing results in HIV prevention trials with FSWs . These results suggest that FSWs ’ risk of acquiring HIV infection might be reduced through the indirect approach of increasing ART coverage in the community Objectives : To measure HIV incidence in a rural area of South Africa with high HIV prevalence and to analyze risk factors for acquisition of HIV using a prospect i ve population -based cohort study . Methods : Data from two rounds ( 2003–2005 ) of a large prospect i ve population -based HIV survey in rural KwaZulu-Natal were used to calculate HIV incidence by sex and 5-year age group . Multiple imputations ( MI ) were used to adjust for selection effects and risk factors for acquiring HIV were examined in Weibull multiple regression . Results : During 5253 person-years at risk , 170 individuals became seropositive . The crude HIV incidence rate per 100 person-years was 3.8 [ 95 % confidence interval ( CI ) , 3.2–4.6 ] in women aged 15–49 years and 2.3 ( 95 % CI , 1.8–3.1 ) in men aged 15–54 years . MI significantly increased the HIV incidence rates both in women and men [ 7.9/100 person-years ( 95 % CI , 7.4–8.4 ) and 5.1/100 person-years ( 95 % CI 4.1–6.2 ) , respectively ] . When holding other factors constant in Weibull multiple regression , the hazard of HIV seroconversion was approximately twice as high in people who were currently unmarried but had a partner than among people who were currently married ( P < 0.001 ) and increased with increasing distance from a government health clinic ( P = 0.051 ) and decreasing distance from a primary road ( P = 0.002 ) . Conclusion : In this high HIV prevalence community in rural South Africa HIV incidence is very high . The present focus on antiretroviral treatment needs to be balanced with a renewed emphasis on HIV prevention for both sexes OBJECTIVE To assess the effect of oral and injectable contraceptive use compared to nonhormonal contraceptive use on HIV acquisition among Southern African women enrolled in a microbicide trial . STUDY DESIGN This is a prospect i ve cohort study using data from women enrolled in HIV Prevention Trials Network protocol 035 . At each quarterly visit , participants were interviewed about self-reported contraceptive use and sexual behaviors and underwent HIV testing . Cox proportional hazards regression was used to assess the effect of injectable and oral hormonal contraceptive use on HIV acquisition . RESULTS The analysis included 2830 participants , of whom 106 became HIV infected ( 4.07 per 100 person-years ) . At baseline , 1546 ( 51 % ) participants reported using injectable contraceptives and 595 ( 21 % ) reported using oral contraceptives . HIV incidence among injectable , oral and nonhormonal contraceptive method users was 4.72 , 2.68 and 3.83 per 100 person-years , respectively . Injectable contraceptive use was associated with a nonstatistically significant increased risk of HIV acquisition [ adjusted hazard ratio (aHR)=1.17 ; 95 % confidence interval ( CI ) 0.70 , 1.96 ] , while oral contraceptive use was associated with a nonstatistically significant decreased risk of HIV acquisition ( aHR=0.76 ; 95 % CI 0.37,1.55 ) . CONCLUSION In this secondary analysis of r and omized trial data , a marginal , but nonstatistically significant , increase in HIV risk among women using injectable hormonal contraceptives was observed . No increased HIV risk was observed among women using oral contraceptives . Our findings support the World Health Organization 's recommendation that women at high risk for acquiring HIV , including those using progestogen-only injectable contraception , should be strongly advised to always use condoms and other HIV prevention measures . IMPLICATION S Among Southern African women participating in an HIV prevention trial , women using injectable hormonal contraceptives had a modest increased risk of HIV acquisition ; however , this association was not statistically significant . Continued research on the relationship between widely used hormonal contraceptive methods and HIV acquisition is essential BACKGROUND The incidence of human immunodeficiency virus ( HIV ) infection remains high among women in sub-Saharan Africa . We evaluated the safety and efficacy of extended use of a vaginal ring containing dapivirine for the prevention of HIV infection in 1959 healthy , sexually active women , 18 to 45 years of age , from seven communities in South Africa and Ug and a. METHODS In this r and omized , double-blind , placebo-controlled , phase 3 trial , we r and omly assigned participants in a 2:1 ratio to receive vaginal rings containing either 25 mg of dapivirine or placebo . Participants inserted the rings themselves every 4 weeks for up to 24 months . The primary efficacy end point was the rate of HIV type 1 ( HIV-1 ) seroconversion . RESULTS A total of 77 participants in the dapivirine group underwent HIV-1 seroconversion during 1888 person-years of follow-up ( 4.1 seroconversions per 100 person-years ) , as compared with 56 in the placebo group who underwent HIV-1 seroconversion during 917 person-years of follow-up ( 6.1 seroconversions per 100 person-years ) . The incidence of HIV-1 infection was 31 % lower in the dapivirine group than in the placebo group ( hazard ratio , 0.69 ; 95 % confidence interval [ CI ] , 0.49 to 0.99 ; P=0.04 ) . There was no significant difference in efficacy of the dapivirine ring among women older than 21 years of age ( hazard ratio for infection , 0.63 ; 95 % CI , 0.41 to 0.97 ) and those 21 years of age or younger ( hazard ratio , 0.85 ; 95 % CI , 0.45 to 1.60 ; P=0.43 for treatment-by-age interaction ) . Among participants with HIV-1 infection , nonnucleoside reverse-transcriptase inhibitor resistance mutations were detected in 14 of 77 participants in the dapivirine group ( 18.2 % ) and in 9 of 56 ( 16.1 % ) in the placebo group . Serious adverse events occurred more often in the dapivirine group ( in 38 participants [ 2.9 % ] ) than in the placebo group ( in 6 [ 0.9 % ] ) . However , no clear pattern was identified . CONCLUSIONS Among women in sub-Saharan Africa , the dapivirine ring was not associated with any safety concerns and was associated with a rate of acquisition of HIV-1 infection that was lower than the rate with placebo . ( Funded by the International Partnership for Microbicides ; Clinical Trials.gov number , NCT01539226 . ) Objective : The objective of this study was to underst and temporal trends in the contribution of different genital tract infections to HIV incidence over 20 years of follow-up in a cohort of high-risk women . Design : A prospect i ve cohort study . Methods : We performed monthly evaluations for HIV , vaginal yeast , bacterial vaginosis , Trichomonas vaginalis , Neisseria gonorrhoeae , nonspecific cervicitis , herpes simplex virus type two ( HSV-2 ) , genital ulcer disease ( GUD ) and genital warts . We used Cox regression to evaluate the association between sexually transmitted infections ( STIs ) and HIV acquisition over four time periods ( 1993–1997 , 1998–2002 , 2003–2007 , 2008–2012 ) . Models were adjusted for age , workplace , sexual risk behaviour , hormonal contraceptive use and other STIs . The result ing hazard ratios were used to calculate population attributable risk percentage ( PAR% ) . Results : Between 1993 and 2012 , 1964 women contributed 6135 person-years of follow-up . The overall PAR% for each infection was prevalent HSV-2 ( 48.3 % ) , incident HSV-2 ( 4.5 % ) , bacterial vaginosis ( 15.1 % ) , intermediate microbiota ( 7.5 % ) , vaginal yeast ( 6.4 % ) , T. vaginalis ( 1.1 % ) , N. gonorrhoeae ( 0.9 % ) , nonspecific cervicitis ( 0.7 % ) , GUD ( 0.8 % ) and genital warts ( −0.2 % ) . Across the four time periods , the PAR% for prevalent HSV-2 ( 40.4 % , 61.8 % , 58.4 % , 48.3 % ) and bacterial vaginosis ( 17.1 % , 19.5 % , 14.7 % , 17.1 % ) remained relatively high and had no significant trend for change over time . The PAR% for trichomoniasis , gonorrhoea , GUD and genital warts remained less than 3 % across the four periods . Conclusion : Bacterial vaginosis and HSV-2 have consistently been the largest contributors to HIV acquisition risk in the Mombasa Cohort over the past 20 years . Interventions that prevent these conditions would benefit women 's health and could reduce their risk of becoming infected with HIV BACKGROUND Cash transfers have been proposed as an intervention to reduce HIV-infection risk for young women in sub-Saharan Africa . However , scarce evidence is available about their effect on reducing HIV acquisition . We aim ed to assess the effect of a conditional cash transfer on HIV incidence among young women in rural South Africa . METHODS We did a phase 3 , r and omised controlled trial ( HPTN 068 ) in the rural Bushbuckridge subdistrict in Mpumalanga province , South Africa . We included girls aged 13 - 20 years if they were enrolled in school grade s 8 - 11 , not married or pregnant , able to read , they and their parent or guardian both had the necessary documentation necessary to open a bank account , and were residing in the study area and intending to remain until trial completion . Young women ( and their parents or guardians ) were r and omly assigned ( 1:1 ) , by use of numbered sealed envelopes containing a r and omisation assignment card which were numerically ordered with block r and omisation , to receive a monthly cash transfer conditional on school attendance ( ≥80 % of school days per month ) versus no cash transfer . Participants completed an Audio Computer-Assisted Self-Interview ( ACASI ) , before test HIV counselling , HIV and herpes simplex virus (HSV)-2 testing , and post-test counselling at baseline , then at annual follow-up visits at 12 , 24 , and 36 months . Parents or guardians completed a Computer-Assisted Personal Interview at baseline and each follow-up visit . A stratified proportional hazards model was used in an intention-to-treat analysis of the primary outcome , HIV incidence , to compare the intervention and control groups . This study is registered at Clinical Trials.gov ( NCT01233531 ) . FINDINGS Between March 5 , 2011 , and Dec 17 , 2012 , we recruited 10 134 young women and enrolled 2537 and their parents or guardians to receive a cash transfer programme ( n=1225 ) or not ( control group ; n=1223 ) . At baseline , the median age of girls was 15 years ( IQR 14 - 17 ) and 672 ( 27 % ) had reported to have ever had sex . 107 incident HIV infections were recorded during the study : 59 cases in 3048 person-years in the intervention group and 48 cases in 2830 person-years in the control group . HIV incidence was not significantly different between those who received a cash transfer ( 1·94 % per person-years ) and those who did not ( 1·70 % per person-years ; hazard ratio 1·17 , 95 % CI 0·80 - 1·72 , p=0·42 ) . INTERPRETATION Cash transfers conditional on school attendance did not reduce HIV incidence in young women . School attendance significantly reduced risk of HIV acquisition , irrespective of study group . Keeping girls in school is important to reduce their HIV-infection risk . FUNDING National Institute of Allergy and Infectious Diseases , National Institute of Mental Health of the National Institutes of Health Background HIV risk remains unacceptably high among adolescent girls and young women ( AGYW ) in southern and eastern Africa , reflecting structural and social inequities that drive new infections . In 2015 , PEPFAR ( the United States President ’s Emergency Plan for AIDS Relief ) with private-sector partners launched the DREAMS Partnership , an ambitious package of interventions in 10 sub-Saharan African countries . DREAMS aims to reduce HIV incidence by 40 % among AGYW over two years by addressing multiple causes of AGYW vulnerability . This protocol outlines an impact evaluation of DREAMS in four setting s. Methods To achieve an impact evaluation that is credible and timely , we describe a mix of methods that build on longitudinal data available in existing surveillance sites prior to DREAMS roll-out . In three long-running surveillance sites ( in rural and urban Kenya and rural South Africa ) , the evaluation will measure : ( 1 ) population -level changes over time in HIV incidence and socio-economic , behavioural and health outcomes among AGYW and young men ( before , during , after DREAMS ) ; and ( 2 ) causal pathways linking uptake of DREAMS interventions to ‘ mediators ’ of change such as empowerment , through to behavioural and health outcomes , using nested cohort studies with sample s of ~ 1000–1500 AGYW selected r and omly from the general population and followed for two years . In Zimbabwe , where DREAMS includes an offer of pre-exposure HIV prophylaxis ( PrEP ) , cohorts of young women who sell sex will be followed for two years to measure the impact of ‘ DREAMS+PrEP ’ on HIV incidence among young women at highest risk of HIV . In all four setting s , process evaluation and qualitative studies will monitor the delivery and context of DREAMS implementation . The primary evaluation outcome is HIV incidence , and secondary outcomes include indicators of sexual behavior change , and social and biological protection . Discussion DREAMS is , to date , the most ambitious effort to scale-up combinations or ‘ packages ’ of multi-sectoral interventions for HIV prevention . Evidence of its effectiveness in reducing HIV incidence among AGYW , and demonstrating which aspects of the lives of AGYW were changed , will offer valuable lessons for replication Cost-Benefit of ART In the battle to control HIV , mass antiretroviral treatment ( ART ) costs $ 500 to $ 900 per person per year . Bor et al. ( p. 961 ) calculated the impact of intensifying ART on the life expectancy of people living in rural KwaZulu Natal . The date s of death were collected from a population of about 100,000 people during 2000–2011 : Four years before and 8 years after the scaling up of ART . Life expectancy of adults increased by more than 11 years after ART was exp and ed , and the economic value of the lifetimes gained were calculated to far exceed the cost of treatment . Tanser et al. ( p. 966 ) followed nearly 17,000 HIV-uninfected individuals in KwaZulu-Natal over an 8-year period . Holding other HIV risk factors constant , individual HIV acquisition risk declined significantly with increasing ART coverage of HIV-infected people . The risk of acquiring HIV is reduced in rural communities via large-scale delivery of antiretroviral therapy . The l and mark HIV Prevention Trials Network ( HPTN ) 052 trial in HIV-discordant couples demonstrated unequivocally that treatment with antiretroviral therapy ( ART ) substantially lowers the probability of HIV transmission to the HIV-uninfected partner . However , it has been vigorously debated whether substantial population -level reductions in the rate of new HIV infections could be achieved in " real-world " sub-Saharan African setting s where stable , cohabiting couples are often not the norm and where considerable operational challenges exist to the successful and sustainable delivery of treatment and care to large numbers of patients . We used data from one of Africa 's largest population -based prospect i ve cohort studies ( in rural KwaZulu-Natal , South Africa ) to follow up a total of 16,667 individuals who were HIV-uninfected at baseline , observing individual HIV seroconversions over the period 2004 to 2011 . Holding other key HIV risk factors constant , individual HIV acquisition risk declined significantly with increasing ART coverage in the surrounding local community . For example , an HIV-uninfected individual living in a community with high ART coverage ( 30 to 40 % of all HIV-infected individuals on ART ) was 38 % less likely to acquire HIV than someone living in a community where ART coverage was low ( < 10 % of all HIV-infected individuals on ART ) |
13,803 | 18,254,089 | The data that are available from the studies provide only a small insight into the long-term efficacy and harm profiles of these treatments . | BACKGROUND Herb and plant based preparations are a popular treatment for asthma , although there remain concerns as to their efficacy and safety .
In Western societies , motivations for using such treatments may be both positive and negative , with their perceived safety and dissatisfaction with conventional medicine among them .
In China such treatments are more commonly used and many compounds considered ' conventional ' are derived from herbs or plants .
OBJECTIVES To assess the efficacy and safety of herb and plant extracts in the management of chronic asthma . | BACKGROUND There are few data on the use of alternative therapies in adult asthma and their impact on health outcomes . OBJECTIVE The objective of this study was to study the prevalence and morbidity of asthma self-treatment with herbs , coffee or black tea , and over-the-counter ( OTC ) medications containing ephedrine or epinephrine . METHODS We carried out a cross-sectional analysis of interview data for 601 adults with asthma recruited from a r and om sample of pulmonary and allergy specialists . We estimated the 12-month prevalence of reported use of herbal products , coffee or black tea , or OTC products to self-treat asthma and their association with emergency department visits and hospitalization . RESULTS Herbal asthma self-treatment was reported by 46 ( 8 % ; 95 % confidence interval [ CI ] 6 % to 10 % ) ; coffee or black tea self-treatment by 36 ( 6 % ; 95 % CI 4 % to 8 % ) , epinephrine or ephedrine OTC use by 36 ( 6 % ; 95 % CI 4 % to 8 % ) , and any of the three practice s by 98 subjects ( 16 % ; 95 % CI 13 % to 19 % ) . Adjusting for demographic and illness covariates , herbal use ( odds ratio [ OR ] 2.5 ; 95 % CI 1.1 to 5.6 ) and coffee or black tea use ( OR 3.1 ; 95 % CI 1.2 to 7.8 ) were associated with asthma hospitalization ; OTC use was not ( OR 0.8 ; 95 % CI 0.3 to 2.5 ) . CONCLUSIONS Even among adults with access to specialty care for asthma , self-treatment with nonprescription products was common and was associated with increased risk of reported hospitalization . This association does not appear to be accounted for by illness severity or other disease covariates . It may reflect delay in utilization of more efficacious treatments Difficultes ethiques rencontrees pour l'organisation d'experimentations cliniques concernant l'asthme chez l'enfant ( un appareil pour inhalation de corticosteroides , une method e d'immunotherapie , une method e de desensibilisation Asthma is characterized as a chronic inflammatory process . Pycnogenol((R ) ) , a bioflavonoid mixture extracted from Pinus maritima , is known to scavenge free radicals while possessing antioxidant and antiinflammatory properties . The objective of this study was to evaluate the efficiency of this agent in a r and omized , double-blinded , placebo-controlled , crossover study in patients with varying asthma severity . Twenty-six patients who fulfilled the American Thoracic Society criteria for asthma were enrolled in the study . Medical history , physical examination , blood sample analyses , and spirometric values were obtained at baseline , 4 weeks , and 8 weeks . The patients were r and omly assigned to receive either 1 mg/lb/day ( maximum 200 mg/day ) Pycnogenol or placebo for the first period of 4 weeks and then crossed over to the alternate regimen for the next 4 weeks . No adverse effects were observed related to the study drug . Within the contingent of 22 patients who completed the study , almost all responded favorably to Pycnogenol in contrast to placebo . Pycnogenol treatment also significantly reduced serum leukotrienes compared with placebo . The results of this pilot study indicate that Pycnogenol may be a valuable nutraceutical in the management of chronic asthma . We recommend that further clinical trials be conducted in larger groups of asthmatics to establish its efficacy OBJECTIVE To explore the mechanism of acupoint electro-superconducting therapy with Chinese herbal drugs contained pad in treating children asthma . METHODS Sixty asthma children in the mild to moderate stage of asthma attack were r and omly divided into two groups , the treated group and the control group . Besides the basic treatment , acupoint electro-superconducting therapy with the pad containing Chinese herbal drugs was applied to the treated group , and to the control group the same therapy but with pad of placebo was applied , seven days as a course of treatment . The peak exhalation force ( PEF ) was measured daily , and the cytokines , interleukin-10 ( IL-10 ) and interferon-gamma ( IFN-gamma ) were determined before and after treatment . RESULTS No significant difference was found in the ratio of patients ' PEF to the normal predicted value between the two groups before treatment ( P > 0.05 ) . But on the fourth day of the treatment course , the increase of PEF in the treated group was more obvious than that in the control group ( P < 0.05 ) . The IL-10 levels of two groups were raised after ending the treatment course , but the increment in the treated group was more obvious ( P < 0.01 ) . However , the changes of IFN-gamma levels after treatment showed insignificant difference between the two groups ( P > 0.05 ) . CONCLUSION Acupoint electro-superconducting therapy with Chinese herbal drugs contained pad is helpful to improve the pulmonary function of children with asthma , it could also increase the serum IL-10 level in attack stage of the asthma children The efficacy and tolerability of a butterbur root extract ( Petadolex ) for the treatment of asthma was analyzed in a prospect i ve , non-r and omized , open trial . Subjects included 64 adults and 16 children/adolescents treated for two months with the extract , followed by two months during which the intake of the extract was optional . Concomitant asthma medication was permitted . The number , duration , and severity of asthma attacks decreased , while peak flow , forced expiratory volume ( FEV1 ) , and all measured symptoms improved during therapy . In addition , more than 40 percent of patients using asthma medications at baseline reduced intake of these medications by the end of the study . This study suggests the Petasites hybridus extract Petadolex is an effective and safe therapy for the treatment of asthma CONTEXT A prior national survey documented the high prevalence and costs of alternative medicine use in the United States in 1990 . OBJECTIVE To document trends in alternative medicine use in the United States between 1990 and 1997 . DESIGN Nationally representative r and om household telephone surveys using comparable key questions were conducted in 1991 and 1997 measuring utilization in 1990 and 1997 , respectively . PARTICIPANTS A total of 1539 adults in 1991 and 2055 in 1997 . MAIN OUTCOMES MEASURES Prevalence , estimated costs , and disclosure of alternative therapies to physicians . RESULTS Use of at least 1 of 16 alternative therapies during the previous year increased from 33.8 % in 1990 to 42.1 % in 1997 ( P < or = .001 ) . The therapies increasing the most included herbal medicine , massage , megavitamins , self-help groups , folk remedies , energy healing , and homeopathy . The probability of users visiting an alternative medicine practitioner increased from 36.3 % to 46.3 % ( P = .002 ) . In both surveys alternative therapies were used most frequently for chronic conditions , including back problems , anxiety , depression , and headaches . There was no significant change in disclosure rates between the 2 survey years ; 39.8 % of alternative therapies were disclosed to physicians in 1990 vs 38.5 % in 1997 . The percentage of users paying entirely out-of-pocket for services provided by alternative medicine practitioners did not change significantly between 1990 ( 64.0 % ) and 1997 ( 58.3 % ) ( P=.36 ) . Extrapolations to the US population suggest a 47.3 % increase in total visits to alternative medicine practitioners , from 427 million in 1990 to 629 million in 1997 , thereby exceeding total visits to all US primary care physicians . An estimated 15 million adults in 1997 took prescription medications concurrently with herbal remedies and /or high-dose vitamins ( 18.4 % of all prescription users ) . Estimated expenditures for alternative medicine professional services increased 45.2 % between 1990 and 1997 and were conservatively estimated at $ 21.2 billion in 1997 , with at least $ 12.2 billion paid out-of-pocket . This exceeds the 1997 out-of-pocket expenditures for all US hospitalizations . Total 1997 out-of-pocket expenditures relating to alternative therapies were conservatively estimated at $ 27.0 billion , which is comparable with the projected 1997 out-of-pocket expenditures for all US physician services . CONCLUSIONS Alternative medicine use and expenditures increased substantially between 1990 and 1997 , attributable primarily to an increase in the proportion of the population seeking alternative therapies , rather than increased visits per patient The aim of this study was to evaluate the efficacy and safety of a Chinese herbal formula modified Mai-Men-Dong-Tang ( mMMDT ) for treatment of persistent , mild-to-moderate asthma . A total of 100 asthmatic patients were enrolled and assigned to three treatment groups in this double-blind , r and omized , placebo-controlled clinical trial . Over a period of 4 months , patients in groups A and B received 80 and 40 mg/kg/day of mMMDT , while those in group C received a placebo . Efficacy variables included changes in forced expiratory volume in 1 s ( FEV1 ) , symptom score , serum total immunoglobulin E ( IgE ) , and dust mite-specific IgE. Safety assessment s included complete blood count , and liver and kidney function . Relative to baseline , significantly greater increases in FEV1 were demonstrated for both A and B groups in comparison with the placebo-treated analog ( both p < 0.05 ) . Further , similar improvements in symptom score were observed for both mMMDT treatment groups . The serum total IgE for group A showed a decreasing tendency after treatment but no statistical difference was noted . Furthermore , no drug-related adverse effects were reported . Blood test , and liver and kidney function were within normal range during the study , with no marked changes demonstrated over time . In conclusion , the Chinese herbal formula mMMDT provided improvements in lung function and relieved asthma symptoms in our sample of patients . Given its efficacy and safety , we consider mMMDT a credible treatment regimen for persistent , mild-to-moderate asthma Alternative medicine use has increased at a remarkable pace all over the world in recent years . Although herbal medicine for the treatment of asthma is becoming the focus of public attention , r and omized studies had not been performed , even in Eastern countries including Japan . This study was design ed to investigate whether one of the Japanese government approved herbal complexes Saiboku-to ( TJ-96 ) is effective for the treatment of atopic asthma , and to investigate whether this protective activity is associated with a reduction in eosinophilic inflammation . A double-blind , r and omized , crossover design was used . Subjects received 2.5 g of TJ-96 or placebo orally 3 times daily for 4 weeks and then , after a washout period of at least 4 weeks , crossed over to receive the alternative treatment . We assessed the effects of pretreatment with TJ-96 on bronchoconstriction precipitated by inhalation of methacholine . Furthermore , eosinophil counts and measurement of eosinophilic cationic protein ( ECP ) were performed . After 4 weeks of treatment with TJ-96 , values of PC20 -methacholine significantly improved in the treatment with TJ-96 . Also , patients ' symptoms , blood eosinophils , serum ECP , sputum eosinophils , and sputum ECP were significantly decreased . Our results suggest that TJ-96 has an antiinflammatory effect on bronchial eosinophilic infiltration . This study raises further interesting therapeutic possibilities and argues for further trials of new approaches to the treatment of asthma Essential fatty acids are cl aim ed to have positive effects in atopic diseases . In a double blind , placebo controlled , parallel group study 58 out of 60 children , with atopic dermatitis and the need for regular treatment with topical skin steroids , completed a 16 weeks ' treatment period with either Epogam evening primrose oil or placebo capsules . Twenty two of these subjects also had asthma . The parents used diaries to record symptom scores and concomitant medication . Peak expiratory flow was measured and disease activity was monitored by the clinician every four weeks . The plasma concentrations of essential fatty acids increased significantly in the group treated with Epogam capsules . The study demonstrated significant improvements of the eczema symptoms but no significant difference was found between the placebo and the Epogam groups . No therapeutic effect was shown on asthma symptoms or fidget Dietary gammalinolenic acid ( GLA ) , a potent inhibitor of 5-lipoxygenase ( 5-LOX ) and suppressor of leukotriene B4 ( LTB4 ) , can attenuate the clinical course of rheumatoid arthritics , with negligible side effects . Since Zileuton , also an inhibitor of 5-LOX , attenuates asthma but with an undesirable side effect , we investigated whether dietary GLA would suppress bio synthesis of PMN-LTB4 isolated from asthma patients and attenuate asthma . Twenty-four mild-moderate asthma patients ( 16 - 75 years ) were r and omized to receive either 2.0 g daily GLA ( borage oil ) or corn oil ( placebo ) for 12 months . Blood drawn at 3 months intervals was used to prepare sera for fatty acid analysis , PMNs for determining phospholipid fatty acids and for LTB4 generation . Patients were monitored by daily asthma scores , pulmonary function , and exhaled NO . Ingestion of daily GLA ( i ) increased DGLA ( GLA metabolite ) in PMN-phospholipids ; ( ii ) increased generation of PMN-15-HETrE ( 5-LOX metabolite of DGLA ) . Increased PMN-DGLA/15-HETrE paralleled the decreased PMN generation of proinflammatory LTB4 . However , the suppression of PMN-LTB4 did not reveal statistically significant suppression of the asthma scores evaluated . Nonetheless , the study demonstrated dietary fatty acid modulation of endogenous inflammatory mediators without side effects and thus warrant further explorations into the roles of GLA at higher doses , leukotrienes and asthma OBJECTIVE To observe the therapeutic effect of Zhifeng Huatan Pingxiao recipe ( ZHPR ) in treating attack stage of child asthma . METHODS Sixty child asthma patients with attack of mild and moderate degree were r and omly divided into the treated group ( 40 patients treated with ZHPR ) and the control group ( 20 patients treated with western medicine ) . The therapeutic effect and laboratory indexes , including peripheral eosinophil count ( EOS ) , serum immunoglobulin E ( IgE ) and plasma endothelin ( ET ) , before and after treatment were observed . RESULTS The total effective rate in the treated group was 72.5 % , which was not different to that in the control group ( P > 0.05 ) . The therapeutic effect between different TCM types ( heat and cold types ) in the treated group was not different significantly ( P > 0.05 ) . ET , IgE and EOS levels all lowered after treatment in the treated group , but as compared with those in the control group , the difference was insignificant ( P > 0.05 ) . CONCLUSION The therapeutic effect of ZHPR in treating child asthma attack stage is equivalent to that of western medicine , it shows actions in improving laboratory indexes We have studied the effect of inhaled ouabain on resting bronchomotor tone and histamine responsiveness in eight asthmatic patients in an attempt to clarify the role of Na/K ATPase in airway reactivity . Doses ranged from 50 micrograms to 5000 micrograms and were given in a placebo controlled , double blind manner . Baseline FEV1 was recorded prior to inhalation and at intervals up to 30 min thereafter . At 30 min , a histamine provocation test was performed and results expressed as that concentration producing a 20 % fall in FEV1 . Maximum fall in FEV1 was not significantly different between placebo or any dose of ouabain , ranging from 4.3%-8.2 % ( p greater than 0.06 ) nor was histamine reactivity altered significantly ( geometric mean range 0.17 mg-0.29 mg [ p greater than 0.2 ] ) . Unlike animal studies therefore , we have been unable to demonstrate any effect of Na/K ATPase inhibition on airway reactivity in vivo The gum resin of Boswellia serrata , known in Indian Ayurvedic system of medicine as Salai guggal , contains boswellic acids , which have been shown to inhibit leukotriene bio synthesis . In a double-blind , placebo-controlled study forty patients , 23 males and 17 females in the age range of 18 - 75 years having mean duration of illness , bronchial asthma , of 9.58 + /- 6.07 years were treated with a preparation of gum resin of 300 mg thrice daily for a period of 6 weeks . 70 % of patients showed improvement of disease as evident by disappearance of physical symptoms and signs such as dyspnoea , rhonchi , number of attacks , increase in FEV subset1 , FVC and PEFR as well as decrease in eosinophilic count and ESR . In the control group of 40 patients 16 males and 24 females in the age range of 14 - 58 years with mean of 32.95 + /- 12.68 were treated with lactose 300 mg thrice daily for 6 weeks . Only 27 % of patients in the control group showed improvement . The data show a definite role of gum resin of Boswellia serrata in the treatment of bronchial asthma The aqueous extract of propolis has been formulated as a nutritional food product and administered , as an adjuvant to therapy , to patients with mild to moderate asthma daily for 2 months in the framework of a comparative clinical study in parallel with a placebo preparation . The diagnosis of asthma was made according to the criteria of patient classification of the National Institutes of Health and Global Initiative for Asthma Management . At inclusion , the pulmonary forced expiratory volume in the first second ( FEV1 ) as a percentage of the forced vital capacity ( FVC ) was more than 80 % in mild persistent cases , and between 60 and 80 % in moderate persistent cases , showing an increase in the degree of reversibility of > 15 % in FEV1 . All patients were on oral theophylline as controller therapy , none was receiving oral or inhaled corticosteroids , none had other comorbidities necessitating medical treatment , and all were from a middle‐class community and had suffered from asthma for the last 2–5 years . Twenty‐four patients received the placebo , with one drop‐out during the study , while 22 received the propolis extract , with no drop‐outs . The age range of the patients was 19–52 years ; 36 were male and 10 female . The number of nocturnal attacks was recorded on a weekly basis , while pulmonary function tests were performed on all patients at the beginning of the trial , 1 month later and at the termination of the trial . Immunological parameters , including various cytokines and eicosanoids known to play a role in asthma , were measured in all patients at the beginning of the trial and 2 months later . Analysis of the results at the end of the clinical study revealed that patients receiving propolis showed a marked reduction in the incidence and severity of nocturnal attacks and improvement of ventilatory functions . The number of nocturnal attacks dropped from an average of 2.5 attacks per week to only 1 . The improvement in pulmonary functions was manifested as a nearly 19 % increase in FVC , a 29.5 % increase in FEV1 , a 30 % increase in peak expiratory flow rate ( PEFR ) , and a 41 % increase in the forced expiratory flow rate between 25 and 75 % of the vital capacity ( FEF25‐75 ) . The clinical improvement was associated with decreases by 52 , 65 , 44 and 30 % , respectively , of initial values for the pro‐inflammatory cytokines tumor necrosis factor (TNF)‐α , ICAM‐1 , interleukin (IL)‐6 and IL‐8 , and a 3‐fold increase in the ‘ protective ’ cytokine IL‐10 . The levels of prostagl and ins E2 and F2α and leukotriene D4 were decreased significantly to 36 , 39 , and 28 % , respectively , of initial values . Patients on the placebo preparation showed no significant improvement in ventilatory functions or in the levels of mediators . The findings suggest that the aqueous propolis extract tested is potentially effective as an adjuvant to therapy in asthmatic patients . The benefits may be related to the presence in the extract of caffeic acid derivatives and other active constituents Background : Plant-based medicine is the 3rd most popular choice of both adults ( 11 % ) and children ( 6 % ) suffering from Asthma . While several plant-based formulations have been reported for the treatment of asthma in the past , many authors have published their reservations on clinical trials carried out using complementary and alternative medicines . Objectives : The authors desired to eliminate the shortcomings of the earlier clinical trials carried out by many investigators in a structured study . Therefore , a 12-week r and omized double-blind placebo-controlled clinical study was conducted to investigate the efficacy of a plant-based formulation ( DCBT4567-Astha-15 ) in comparison with oral salbutamol , salbutamol + theophylline and a matching placebo in patients with reversible asthma . Methods : Ninety-four patients between 15 and 50 years of age , showing 15 % improvement in forced expiratory volume in 1 s ( FEV1 ) 15 min after a bronchial challenge of inhaled salbutamol ( 200 µg ) were recruited , and the end point of the study was determined as a 15 % improvement in FEV1 and clinical symptoms like dyspnoea , wheezing , cough , expectoration , disability , sleep disturbances and respiration rate . Results : DCBT4567-Astha-15 , salbutamol and salbutamol + theophylline patients showed statistically significant improvement in FEV1 , while placebo patients did not show any improvement . Fifty percent of DCBT4567-Astha-15 , 48 % of salbutamol , 58 % of salbutamol + theophylline and 26 % of placebo patients showed the desired 15 % improvement in FEV1 . Improved mean FEV1 values at the end of the trial indicated that the salbutamol - theophylline combination was superior followed by salbutamol and DCBT4567-Astha-15 . Clinical symptoms like dyspnoea , wheezing , cough , expectoration , disability , and sleep disturbances were significantly reduced in DCBT4567-Astha-15 patients compared to patients of the other three arms . Conclusions : DCBT4567-Astha-15 was as efficacious as salbutamol ( 12 mg/day ) or salbutamol ( 12 mg/day ) in combination with theophylline ( 200 mg/day ) in the treatment of reversible asthmatics . Quality of life of patients also improved with DCBT4567-Astha-15 drug treatment OBJECTIVE To observe the clinical effect of Chanbei Kechuanping ( CBKCP ) on bronchial asthma and to explore its mechanism . METHODS Ninety-six patients of bronchial asthma were r and omly divided into two groups , the CBKCP treated group and the control group ( treated by Guilong Kechuanning ) . The changes on symptoms and signs of asthma , pulmonary function , T-lymphocyte subsets , plasma soluble interleukin-2 receptor ( sIL-2R ) , thromboxane B2(TXB2 ) and 6-keto-prostagl and in F1 alpha(6-keto-PGF1 alpha ) were observed before and after treatment . RESULTS ( 1 ) The markedly effective rate and effective rate in the CBKCP treated group were higher than those in the control group . The pulmonary function , including 1 second forced expiratory volume , maximum expiratory flow rate and forced lung expiratory vital capacity were all improved in both groups , but the effect was more obvious in the CBKCP treated group . ( 2 ) As compared with the control group , CBKCP showed more obvious effect in lowering sIL-2R , T-lymphocyte subset and raising 6-keto-PGF1 alpha . Experimental study of guinea pig with asthma model showed that CBKCP could markedly prolong the latent time of asthma attack , lower the percentage of mast cells in total cells in the alveoli lavage solution , blood acidophic cell count and degranulation rate of mast cells , and decrease IgE , IL-4 and TXB2 levels as well as increase the 6-keto-PGF1 alpha level . CONCLUSION CBKCP has favorable therapeutic effect on asthma attack , it might play the role partly by regulating the functional T-lymphocyte subsets , reducing the level of IgE , sIL-2R , IL-4 and TXB2 , and increasing the level of 6-keto-PGF1 alpha BACKGROUND Butterbur or Petasites hybridus is an herbal remedy that exhibits antihistamine and antileukotriene activity and has been shown to attenuate the response to adenosine monophosphate challenge in patients with allergic rhinitis and asthma . However , no data are available regarding its effects on the histamine and allergen cutaneous response . OBJECTIVE To evaluate the effects of butterbur compared with fexofenadine and montelukast on the histamine and allergen wheal and flare cutaneous responses . METHODS Atopic patients were r and omized into a double-blind , double-dummy , crossover study to receive for 1 week butterbur , 50 mg twice daily ( 8 AM and 10 PM ) ; fexofenadine , 180 mg once daily ( 10 PM ) , and placebo once daily ( 8 AM ) ; montelukast , 10 mg once daily ( 10 PM ) , and placebo once daily ( 8 AM ) ; or placebo twice daily ( 8 AM and 10 PM ) . Patients attended the department at 10 AM and had measurements of the cutaneous wheal and flare responses to histamine , allergen , and saline control at 10-minute intervals for 60 minutes . RESULTS Twenty patients completed the study . The mean + /- SE histamine wheal and flare responses , respectively , were significantly attenuated ( P < .05 ) by fexofenadine ( 9.4 + /- 1.8 mm2 and 13.5 + /- 3.2 mm2 ) compared with placebo ( 15.5 + /- 3.3 mm2 and 179.8 + /- 74.3 mm2 ) but not by butterbur ( 16.4 + /- 2.1 mm2 and 297.7 + /- 121.2 mm2 ) or montelukast ( 19 + /- 1.9 mm2 and 240.2 + /- 66.6 mm2 ) . The allergen wheal and flare responses , respectively , were also significantly attenuated ( P < .05 ) by fexofenadine ( 31.1 + /- 6.3 mm2 and 256.9 + /- 86.5 mm2 ) compared with placebo ( 65.4 + /- 15.2 mm2 and 1,014.5 + /- 250.0 mm2 ) but not by butterbur ( 50.4 + /- 9.2 mm2 and 1,110.3 + /- 256.1 mm2 ) or montelukast ( 58.8 + /- 9.1 mm2 and 1,463.6 + /- 295.6 mm2 ) . CONCLUSIONS Butterbur did not produce any significant effects on the histamine and allergen cutaneous response compared with placebo , whereas mediator antagonism with fexofenadine but not montelukast produced significant attenuation . This finding would suggest that butterbur may not be effective in allergic skin disease BACKGROUND Asthma and rhinosinusitis are common medical conditions among adults . Alternative treatments could have important impacts on health status among those individuals with these conditions , but specific prevalence data for these treatments are limited . OBJECTIVE To estimate the prevalence of specific alternative treatment modalities , including herbal agents , ingestion of caffeinated beverages , homeopathy , acupuncture , and massage therapies . DESIGN R and om population telephone sample . SETTING Northern California . PARTICIPANTS Three hundred adults aged 18 to 50 years with self-report of a physician diagnosis of asthma ( n = 125 ) or rhinosinusitis without concomitant asthma ( n = 175 ) . MEASUREMENTS Structured telephone interviews covering demographics and clinical variables , including the following alternative treatments used in the previous 12 months : herbal agents ; caffeine-containing products ; homeopathy ; acupuncture ; aromatherapy ; reflexology ; and massage . RESULTS Any alternative practice was reported by 127 subjects ( 42 % ; 95 % confidence interval [ CI ] , 36 to 48 % ) . Of these , 33 subjects ( 26 % ; 95 % CI , 21 to 31 % ) were not current prescription medication users . Herbal use was reported by 72 subjects ( 24 % ) , caffeine treatment by 54 subjects ( 18 % ) , and other alternative treatments by 66 subjects ( 22 % ) . Taking into account demographic variables , subjects with asthma were more likely than those with rhinitis alone to report caffeine self-treatment for their condition ( odds ratio , 2.5 ; 95 % CI , 1.4 to 4.8 % ) , but herbal use and other alternative treatments did not differ significantly by condition group . CONCLUSION Alternative treatments are frequent among adults with asthma or rhinosinusitis and should be taken into account by health-care providers and public health and policy analysts A double-blind , r and omized , crossover study was done to determine the efficacy of colchicine in 30 atopic children with moderately severe asthma . A constant dose of sustained-release theophylline and salbutamol by inhalation , as needed , was administered to all patients . Compared to placebo , colchicine , 0.5 mg twice daily , significantly reduced morning tightness and nocturnal asthma score . There was , however , no significant difference between colchicine and placebo for cough , daytime asthma , or daily combined symptom scores for each patient . Colchicine did not significantly decrease beta-2 agonist inhaler use when compared with placebo . Similarly , there was no statistically significant difference between placebo and colchicine therapy as far as pulmonary function tests and peak flow reversibility were concerned . Thus , colchicine administered for 4 weeks demonstrated insufficient antiasthma activity . Colchicine-induced clinical improvement that was reported in a previous study may be due to selection of patients with mild asthma symptoms . However , our group , comprised of moderately severe asthmatic patients , did not show a satisfactory clinical response Traditional Chinese medicine has a long history of application in the treatment of bronchial asthma . Solid scientific evidence , however , is not available despite its widespread use among patients worldwide and in Taiwan . To assess the effect of Ding Chuan Tang ( DCT ) in airway hyper-responsiveness ( AHR ) on asthmatic children via r and omized , double blind , placebo-controlled clinical trial . This study enrolled children who were aged 8 - 15 and diagnosed as mild to moderate persistent asthma patients . They were r and omly allocated to receive 6.0 g DCT or placebo daily for 12 wk . Self-recorded daily symptom scores , medication scores , and morning and evening peak expiratory flow rates were returned at the monthly clinic . Pulmonary function test , methacholine challenge test , and serum inflammatory mediators were measured before and at the end of the trial . Fifty-two asthmatic children completed the clinical study . Twenty-eight patients were assigned to the treatment group and 24 to the placebo group . At the end of the treatment period , AHR determined by log PC(20 ) was significantly improved in the DCT group ( 0.51 + /- 1.05 mg/ml vs. 0.26 + /- 0.84 mg/ml , p = 0.034 ) . The total clinical and medication reduced parameters showed improvement in the DCT group ( p = 0.004 ) . The AHR , symptom and medication scores in children with persistent asthma were significantly improved with DCT treat for 12 wk . The results suggested more stable airways achieved with such an add-on complementary therapy A r and omized , placebo‐controlled , double‐blind study involving 60 subjects , aged 6–18 years old , was conducted over a period of 3 months to determine the effect of Pycnogenol ® ( a proprietary mixture of water‐soluble bioflavonoids extracted from French maritime pine ) on mild‐to‐moderate asthma . After baseline evaluation , subjects were r and omized into two groups to receive either Pycnogenol ® or placebo . Subjects were instructed to record their peak expiratory flow with an Assess ® Peak Flow Meter each evening . At the same time , symptoms , daily use of rescue inhalers ( albuterol ) , and any changes in oral medications were also recorded . Urine sample s were obtained from the subjects at the end of the run‐in period , and at 1‐ , 2‐ , and 3‐month visits . Urinary leukotriene C4/D4/E4 was measured by an enzyme immunoassay . Compared with subjects taking placebo , the group who took Pycnogenol ® had significantly more improvement in pulmonary functions and asthma symptoms . The Pycnogenol ® group was able to reduce or discontinue their use of rescue inhalers more often than the placebo group . There was also a significant reduction of urinary leukotrienes in the Pycnogenol ® group . The results of this study demonstrate the efficacy of Pycnogenol ® as an adjunct in the management of mild‐to‐moderate childhood asthma 1 . The effects of a specific PAF acether antagonist ( BN 52063 ) on the response to isocapnic hyperventilation with dry cold air ( ISH study ) and exercise ( EIA study ) were assessed in a single dose and short term treatment study in 10 patients with exercise induced asthma . 2 . ISH challenge was performed twice within 1 h after administration of either placebo , 240 mg BN 52063 p.o . or inhalation of 2.4 mg BN 52063 . Hyperventilation increased Raw from 0.30 + /- 0.02 to 0.89 kPa s l-1 ( P less than 0.001 ) after the first challenge and from 0.28 + /- 0.04 to 0.84 + /- 0.06 kPa s l-1 ( P less than 0.001 ) after the second challenge . Oral pretreatment with BN 52063 did not result in a reduction of bronchoconstriction during both challenges . A significant increase of Raw was noted immediately after inhalation of BN 52063 . An inhibition of PAF induced platelet aggregation ( by a factor of 2 ) occurred after oral administration of BN 52063 after both ISH challenges ( P less than 0.05 ) . No significant inhibition of PAF induced platelet aggregation was seen after inhalation of BN 52063 . At concentrations up to 30 microM in vitro , BN 52063 inhibited PAF induced platelet aggregation in a dose dependent manner . The IC50 of BN 52063 against the aggregating effect of 1 microM PAF was 7.0 + /- 2.1 microM. 3 . In the EIA study the patients were challenged on the third day of treatment with either placebo or 240 mg BN 52063 p.o . or 5 mg BN 52063 by inhalation . Peak expiratory flow rates ( PEFR ) fell by 155 + /- 37 1 min-1 after exercise . ( ABSTRACT TRUNCATED AT 250 WORDS Platelet Activating Factor , PAF-acether , elicits acute and more prolonged inflammatory responses in both experimental animals and man , and is recognised as a possible mediator of asthma . The effect of a specific PAF-acether antagonist , BN 52063 , on the early asthmatic response to inhaled allergen was assessed in a r and omised , double-blind , crossover study in eight atopic asthmatics , who received three days treatment with BN 52063 or placebo , separated by a one week washout . On the third day of treatment , subjects were challenged with nebulised house dust mite or pollen allergen . BN 52063 significantly antagonised early bronchoconstriction and showed a tendency to inhibit residual bronchial hyperreactivity , assessed six hours after allergen challenge by a provocation test to acetylcholine . No side effects were reported during active treatment . This is the first study in man demonstrating the efficacy of a specific PAF-acether antagonist on the immediate response to inhaled allergen challenge in asthmatics . The findings support the possible role of specific PAF-acether antagonists in the treatment of asthma In order to study the effect of strengthening body resistance method on asthmatic attack , asthma patients of Cold type and Heat type were treated with symptomatic treatment ( as control groups ) , and treatment both on the principal and secondary aspect ( as test group ) respectively . The results showed that the markedly effective rates of the test groups of both type were higher than that of the two control groups . In test groups after treatment , the 1 second forced expiratory volume ( FEV1 ) and the maximal expiratory flow increased markedly , the human leucocyte antigen carrying ( HLA-DR+ ) T cell ratio , the basophilic cell releasing capacity ( HBR ) and the T cell hyperplasia response to specific allergen were all reduced . While in the control groups , these criteria had no significant changes after treatment . These results suggested that the strengthening body resistance method displayed an obvious regulating action in relieving attack of asthma The airway and tremor response and cardiovascular and hypokalemic effects of single doses of inhalative fenoterol dry powder capsules ( 0.4 mg ) were compared with the fenoterol metered dose inhaler ( 0.4 mg ) and colforsin ( forskolin ) dry powder capsules ( 10.0 mg ) , a direct activator of the adenylate cyclase system , in 16 patients with asthma . Subjects ( FEV1 ≤ 60 % predicted ) were investigated in a r and omized , double‐masked , placebo‐controlled , four‐period , crossover trial for a 120 minute period . All active drugs caused a significant increase in specific airway conductance ( p < 0.05 ) ; the order of potency ( mean ± SEM maximum increase from baseline ) was fenoterol metered dose inhaler ( 0.51 ± 0.06 sec−1 · kPa−1 ) , fenoterol dry powder capsules ( 0.49 ± 0.07 ) , and colforsin dry powder capsules ( 0.30 ± 0.03 ) . A marked increase in finger tremor amplitude result ed after fenoterol metered dose inhaler only ( 62.93 % ± 10.21 % ; p < 0.05 ) in contrast to fenoterol dry powder capsules ( 15.84 % ± 4.35 % ; p < 0.05 ) and colforsin dry powder capsules ( 12.87 % ± 10.44 % ; p > 0.05 ) . A decrease in plasma potassium was found after fenoterol ( metered dose inhaler > dry powder capsules ; p < 0.05 ) . In conclusion , fenoterol dry powder capsules caused less tremor response and hypokalemic effects than the metered dose inhaler , although the bronchodilator capacity was similar . Colforsin dry powder capsules result ed in a measurable bronchodilatation in patients with asthma Nigella sativa ( black seed ) is an important medicinal herb . In many Arabian , Asian and African countries , black seed oil is used as a natural remedy for a wide range of diseases , including various allergies . The plant 's mechanism of action is still largely unknown . Due to the lack of study data on its efficacy in allergies , four studies on the clinical efficacy of Nigella sativa in allergic diseases are presented . In these studies , a total of 152 patients with allergic diseases ( allergic rhinitis , bronchial asthma , atopic eczema ) were treated with Nigella sativa oil , given in capsules at a dose of 40 to 80 mg/kg/day . The patients scored the subjective severity of target symptoms using a predefined scale . The following laboratory parameters were investigated : IgE , eosinophil count , endogenous cortisol in plasma and urine , ACTH , triglycerides , total cholesterol , LDL and HDL cholesterol and lymphocyte sub population s. The score of subjective feeling decreased over the course of treatment with black seed oil in all four studies . A slight decrease in plasma triglycerides and a discrete increase in HDL cholesterol occurred while the lymphocyte sub population s , endogenous cortisol levels and ACTH release remained unchanged . Black seed oil therefore proved to be an effective adjuvant for the treatment of allergic diseases It has shown recently that Evening Primrose Oil ( Efamol ) produces a significant clinical improvement in atopic eczema . Efamol contains gamma-linolenic acid which is a precursor to PGE1 a more consistent bronchodilator than PGE2 . We have conducted a double blind placebo controlled study in atopic asthmatics given Efamol for an eight week period looking at the control of asthma , including histamine challenge tests . We have found no effect on the asthma or challenge tests although Efamol produced an alteration in fatty acid profile . The patients showed an abnormal fatty acid profile . We speculate that such fatty acid abnormalities could be important in the aetiology of asthma OBJECTIVE To observe the effect and the possible mechanism of Jiexiao Oral Liquid ( JXOL ) in preventing and curing virus induced asthma in children . METHODS One hundred and sixty patients of acute upper respiratory tract infection ( AURTI ) with asthma history were r and omly divided into 2 groups . JXOL was given to the treated group within 24 hrs after occurrence of AURTI symptoms , and virazole of 10 - 15 mg.kg-1.d-1 was given to the control group , the therapeutic course for both groups was 7 days . Changes of clinical symptoms , signs , therapeutic effect , pulmonary function and immuno-globulin in patients were observed . RESULTS The total effective rate of the treated group was 83.8 % , the clinical control rate was 48.8 % , while those in the control group were 62.5 % and 23.8 % respectively , showing significant difference between them ( P < 0.01 ) . JXOL could obviously improve the indexes of forced expiratory volume in one second ( FEV1 ) and peak expiratory flow ( PEF ) , reduce the level of IgE , as compared with those before treatment , the difference was significant ( P < 0.01 or P < 0.05 ) ; it also showed significant difference as compared with those in the control group after treatment . The changes of IgA , IgG and IgM after treatment showed insignificant difference . CONCLUSION JXOL was effective in preventing and curing virus induced asthma in children , it also shows pulmonary function improving and immune regulating effects R and omized , controlled trials ( RCTs ) of herbal interventions often inadequately describe important aspects of their methods ( 1 - 4 ) . Although the quality of reporting of these trials may be improving with time , many still lack important information , particularly about the composition of the herbal intervention ( 4 , 5 ) . Crude herbal drugs are natural products and their chemical composition varies depending on several factors , such as geographic source of the plant material , climate in which it was grown , and time of harvest . Commercially available herbal medicinal products also vary in their content and concentration of chemical constituents from batch to batch and when products containing the same herbal ingredient are compared among manufacturers ( 6 - 14 ) . Even when herbal products are st and ardized for content of known active or marker compounds to achieve more consistent pharmaceutical quality , there is variation in the concentrations of other constituents . These variations can result in differences in pharmacologic activity in vitro ( 15 ) and in bioavailability in humans ( 16 ) . Mindful of these issues , we elaborated on the 22-item checklist of the Consoli date d St and ards of Reporting Trials ( CONSORT ) statement ( 17 ) to help authors and editors improve reporting of RCTs of herbal interventions . Methods We developed these reporting recommendations in 3 phases that included premeeting item generation , a consensus meeting , and postmeeting feedback . The individuals who participated are listed in the Appendix . To generate items , 1 investigator conducted telephone interviews of 16 participants with expertise in the method and reporting of RCTs ( 5 participants ) , pharmacognosy ( 4 participants ) , herbal medicinal products ( 5 participants ) , medical statistics ( 1 participant ) , and herbal product manufacturing ( 1 participant ) . The investigator asked participants to suggest revisions to existing CONSORT checklist items and also to additional items required for reporting trials of herbal interventions . He asked participants to nominate revisions or new items on the basis of empirical evidence that not reporting the item would bias estimates of treatment effect . When no empirical evidence was available , commonsense reasoning was acceptable . After completing all telephone calls , the investigator thematically grouped items and circulated them by e-mail to each participant for review . Fourteen participants attended the consensus meeting . The meeting began with a review of the premeeting checklist item suggestions . We emphasized minimizing item elaborations and additions and basing elaborations on evidence whenever possible . Each item suggestion was presented and followed by debate for its inclusion , deletion , or modification . This process was repeated until all items were review ed and a consensus emerged . After the consensus meeting , we circulated a draft summary report to all participants to ensure that it accurately represented decisions made during the consensus meeting . We then circulated the report to the wider CONSORT Group for input and revised it on the basis of their suggestions . Ethical approval was obtained from The University of Toronto Health Sciences Ethics Review Committee on 23 January 2004 . Financial support for the consensus meeting was provided by the Canadian Institutes of Health Research . The funding body had no role in the design , conduct , or analysis of this study and did not influence the decision to su bmi t the manuscript for publication . All research ers are independent of the funders . Results The group did not recommend any new CONSORT checklist items or modifications in the CONSORT flow diagram . We did , however , elaborate on 9 of the 22 CONSORT checklist items to enhance their relevance to trials of herbal interventions ( Table , Figure ; Appendix Table ) , including minor recommendations for 8 items ( item 1 [ title and abstract ] , item 2 [ background ] , item 3 [ participants ] , item 6 [ outcomes ] , item 15 [ baseline data ] , item 20 [ interpretation ] , item 21 [ generalizability ] , and item 22 [ overall evidence ] ) and detailed recommendations for 1 item ( item 4 [ interventions ] ) . Table . Proposed Elaboration of CONSORT Checklist Item 4 for Reporting R and omized , Controlled Trials of Herbal Medicine Interventions Figure . The high-pressure liquid chromatography chemical fingerprint for the extract of Ginkgo biloba L Appendix Table . Proposed Elaborations of CONSORT Items for R and omized , Controlled Trials of Herbal Medicine Interventions The Table shows the detailed recommendations for item 4 and an example of good reporting related to each recommendation . These recommendations begin with the words where applicable to indicate that all information suggested may not be applicable to every type of herbal medicine intervention . For example , an herbal medicinal product comprising crude herbal material ( for example , leaves and stems ) simply prepared as a tea or decoction does not require description of the type and concentration of solvent used and the ratio of herbal drug to extract ( item 4B.3 ) . Also , not every herbal medicine intervention will have a finished product or extract name or manufacturer ( item 4A.2 ) , but instead may be made by the investigators specifically for the study . In such circumstances , all methods used in preparing and formulating the product must be reported . Similarly , item 4F is not required for herbal interventions when the practitioner is not a part of the intervention . With these exceptions , we recommend that all information shown in the Table be reported for all herbal interventions . Discussion We developed recommendations to be used in conjunction with the existing CONSORT checklist when reporting RCTs of herbal interventions . In particular , we thought it imperative that reports of RCTs provide clear and complete descriptions of the herbal intervention . We think that our recommendations might also be relevant for reporting herbal interventions in other research design s , whether pre clinical ( for example , in vivo or in vitro ) or clinical ( for example , N of 1 trials ) , and refer interested readers to a detailed explanatory document that further describes each of our recommendations and provides additional examples of good reporting ( 22 ) . We hope that authors find our recommendations instructive and that journals will endorse their use and modify their instructions to authors accordingly Although some formulae of traditional Chinese medicines ( TCM ) have been used for antiasthma treatment , few of them have had sufficient discussion on their efficacy , safety and mechanisms . In this study , the availability of the TCM formula STA-1 for the treatment of allergic asthma was investigated by conducting a double-blind , placebo-controlled and r and omized trial . One hundred and twenty patients between the ages of 5 to 20 years with mild-to-moderate asthma were included . These patients were treated with either STA-1 or placebo in a dose of 80 g/kg/day and were administered twice daily for 6 months . The main outcome measures were a daily diary record of symptoms , supplementary bronchodilator and glucocorticoid treatment , changes of pulmonary function ( forced expiratory volume in 1 s ) , changes of total and Dermatophagoides pteronyssinus (DP)-specific IgE and side effects . The results showed a statistically significant reduction of symptom scores , systemic steroid dose , total IgE and specific IgE in the STA-1 group . Furthermore , STA-1 also improved the pulmonary lung function FEV(1 ) compared with the placebo group and only minimal side effects were shown . These results suggested that STA-1 is available for the treatment of mild-to-moderate chronic asthma Abstract Results of a crossover double-blind trial on 110 bronchial asthma patients with leaves of Tylophora indica and of spinach ( placebo ) are presented . The dose was one leaf daily for 6 days to be chewed and swallowed early in the morning . A 12 week follow-up was done . At the end of one week , 62 per cent of the Tylophora group had complete to moderate relief in symptoms , as compared with 28 per cent of the placebo group . At 4 weeks , the respective figures were 37 per cent and 11 per cent ; at 8 weeks , 30 per cent and 7.4 per cent ; and at 12 weeks , 16 per cent and zero per cent . The incidence of side effects , such as sore mouth , loss of taste for salt , and /or morning nausea and vomiting was 53 per cent in the Tylophora group and 9 per cent in the placebo group . There appeared to be a correlation between the incidence of side effects and degree of improvement . After crossover at the end of one week , 50 per cent of the Tylophora group had complete to moderate relief as compared with 11 per cent of the placebo group . The authors are not aware of any other drug which , when administered in a small dose once a day for 6 days only , will suppress the symptoms of allergic rhinitis and /or asthma for 8 to 12 weeks in a significant number of patients . It is postulated that irritative effects of the juice of the Tylophora leaf on the mucous membranes of the mouth , tongue , and stomach somehow suppress or diminish the response of the nasobronchial tissue to an inhalant allergen through some reflex mechanism In a r and omised single-blind crossover study we assessed the effects of a specific PAF acether antagonist , BN 52063 , on the early asthmatic response to exercise in six patients with exercise induced asthma . After a treatment period of two days an exercise challenge on the third day was preceded by administration of either placebo or BN 52063 240 mg p.o . 3 hours or 5 mg by inhalation 30 minutes before the challenge . After the oral intake of 240 mg BN 52063 there was no effect on the initial exercise induced bronchoconstriction , but the prolonged reduction of PEF was significantly attenuated expressed as a smaller AUC ( p less than 0.02 ) . In the placebo period there was a marked increase in plasma concentrations of both platelet factor 4 ( PF4 ) and beta-thromboglobulin ( beta-TBG ) . Intake of BN 52063 diminished the rise in plasma concentrations of PF4 and beta-TBG after the exercise challenge significantly . The results show that platelet activation after exercise induced asthma was markedly inhibited by BN 52063 , indicating that PAF acts as a mediator in exercise induced asthma Sixteen patients with proven reversible airways obstruction were admitted to a double-blind study to compare the bronchodilator effects of oral delta-1-(trans)-tetrahydrocannabinol ( delta-1-THC ) and salbutamol . Measurements of forced vital capacity , forced expired volume in one second , peak expiratory flow rate , and maximum expiratory flow rate at 50 percent vital capacity after 10 mg oral delta-1-THC did not differ significantly from the effect of placebo , whereas increases after salbutamol were significant . Analyses of mood , pulse rate , blood pressure , and electrocardiogram showed no important changes after oral delta-1-THC . In vitro studies with isolated tracheal muscle indicate that the activity of delta-1-THC is 1,000 times less than the equivalent dose of isoprenaline , and the effect of delta-1-THC is not abolished by beta-adrenoreceptor blocking agents . It is concluded that oral delta-1-THC , at a dose of 10 mg , does not produce clinical ly significant bronchodilatation in patients with reversible airways obstruction BACKGROUND Chinese herbal medicine has a long history of human use . A novel herbal formula , anti-asthma herbal medicine intervention ( ASHMI ) , has been shown to be an effective therapy in a murine model of allergic asthma . OBJECTIVE This study was undertaken to compare the efficacy , safety , and immunomodulatory effects of ASHMI treatment in patients with moderate-severe , persistent asthma with prednisone therapy . METHODS In a double-blind trial , 91 subjects underwent r and omization . Forty-five subjects received oral ASHMI capsules and prednisone placebo tablets ( ASHMI group ) and 46 subjects received oral prednisone tablets and ASHMI placebo capsules ( prednisone group ) for 4 weeks . Spirometry measurements ; symptom scores ; side effects ; and serum cortisol , cytokine , and IgE levels were evaluated before and after treatment . RESULTS Posttreatment lung function was significantly improved in both groups as shown by increased FEV(1 ) and peak expiratory flow findings ( P<.001 ) . The improvement was slightly but significantly greater in the prednisone group ( P<.05 ) . Clinical symptom scores , use of beta(2)-bronchodilators , and serum IgE levels were reduced significantly , and to a similar degree in both groups ( P<.001 ) . T(H)2 cytokine levels were significantly reduced in both treated groups ( P<.001 ) and were lower in the prednisone-treated group ( P<.05 ) . Serum IFN-gamma and cortisol levels were significantly decreased in the prednisone group ( P<.001 ) but significantly increased in the ASHMI group ( P<.001 ) . No severe side effects were observed in either group . CONCLUSION Anti-asthma herbal medicine intervention appears to be a safe and effective alternative medicine for treating asthma . In contrast with prednisone , ASHMI had no adverse effect on adrenal function and had a beneficial effect on T(H)1 and T(H)2 balance Airway hypersecretion is mediated by increased release of inflammatory mediators and can be improved by inhibition of mediator production . We have recently reported that 1.8-cineol ( eucalyptol ) which is known as the major monoterpene of eucalyptus oil suppressed arachidonic acid metabolism and cytokine production in human monocytes . Therefore , the aim of this study was to evaluate the anti-inflammatory efficacy of 1.8-cineol by determining its prednisolone equivalent potency in patients with severe asthma . Thirty-two patients with steroid-dependent bronchial asthma were enrolled in a double-blind , placebo-controlled trial . After determining the effective oral steroid dosage during a 2 month run-in phase , subjects were r and omly allocated to receive either 200 mg 1.8-cineol t. i.d . or placebo in small gut soluble capsules for 12 weeks . Oral glucocorticosteroids were reduced by 2.5 mg increments every 3 weeks . The primary end point of this investigation was to establish the oral glucocorticosteroid-sparing capacity of 1.8-cineol in severe asthma . Reductions in daily prednisolone dosage of 36 % with active treatment ( range 2.5 - 10 mg , mean : 3.75 mg ) vs. a decrease of only 7 % ( 2.5 - 5 mg , mean : 0.91 mg ) in the placebo group ( P = 0.006 ) were tolerated . Twelve of 16 cineol vs. four out of 16 placebo patients achieved a reduction of oral steroids ( P = 0.012 ) . Long-term systemic therapy with 1.8-cineol has asignificant steroid-saving effect in steroid-depending asthma . This is the first evidence suggesting an anti-inflammatory activity of the monoterpene 1.8-cineol in asthma and a new rational for its use as mucolytic agent in upper and lower airway diseases Menthol ( 2-isopropyl-5-methyl-cyclohexanol ) , a cyclic alcohol widely appreciated for its ability to produce a cooling sensation , has been used as a constituent of food and drink , tobacco and cosmetics . This compound can reduce flatulence and colic pain in patients with irritable bowel syndrome probably through blockade of Ca2 + channels on intestinal smooth muscle ( 1 ) . A recent report indicates that menthol vapour possesses an antitussive action ( 2 ) . The objective of the present study was to investigate the effect of menthol on airway hyperresponsiveness in asthma Xuan Fei Ding Chuan Wan ( [ symbol : see text ] pills for facilitating the flow of the lung-qi to relieve asthma ) and Xiao Chuan Gu Ben Wan ( [ symbol : see text ] pills for treating asthma by consolidating the origin ) were used for treatment of bronchial asthma . The cure rate in the treated group ( n = 600 ) was 81.33 % , significantly higher ( P < 0.01 ) than that in the control group ( n = 164 , with a cure rate of 9.76 % ) BACKGROUND The effects of butterbur ( BB ) , a herbal remedy , as add-on therapy to inhaled corticosteroids in patients with atopic asthma is currently unknown . OBJECTIVE We evaluated the effects of BB , given as add-on therapy to asthmatic patients maintained on inhaled corticosteroids , assessing adenosine monophosphate ( AMP ) bronchoprovocation ( primary outcome variable ) along with other surrogate inflammatory markers such as exhaled nitric oxide , serum eosinophil cationic protein and peripheral blood eosinophil count . METHODS Sixteen atopic asthmatic patients with mean ( st and ard error of mean ) forced expiratory volume in 1 s ( FEV1 ) of 78 (4)% predicted , maintained on their constant dose of inhaled corticosteroids throughout the study , received twice daily for 1 week either BB 25 mg or placebo ( PL ) , in a double-blind , cross-over fashion , with a 1-week washout period prior to each r and omized treatment . Measurements were made at baselines prior to each r and omized treatment and following the r and omized treatment period . RESULTS Baseline values for the primary and secondary outcomes were not significantly different prior to BB and PL . AMP provocative concentration causing a 20 % reduction from baseline FEV1 ( PC20 ) as doubling dilution change from baseline , significantly improved ( P<0.05 ) with BB , 0.6 ( 0.2 ) , compared with PL , -0.1 ( 0.3 ) ; a 0.7 doubling dilution difference . Exhaled nitric oxide as change from baseline was significantly reduced ( P<0.05 ) with BB , -1.2 ( 0.8 ) p.p.b . , compared with PL , 0.5 ( 0.4 ) p.p.b . Both serum eosinophil cationic protein and peripheral blood eosinophil count as change from baseline were also significantly suppressed ( P<0.05 ) with BB , -3.9 ( 3.3 ) microg/L , -31 (28)x106/L compared with PL , 3.3 ( 2.5 ) microg/L , 38 (16)x106/L , respectively . CONCLUSION Chronic dosing with BB conferred complementary anti-inflammatory activity in atopic asthmatic patients maintained on inhaled corticosteroids . Further studies are now required to assess the potential role for BB as either monotherapy in milder patients or add-on therapy in more severe asthmatics To determine the role of Na/K ATPase in determining bronchial reactivity in man , we studied the effect of 1 mg inhaled ouabain on histamine reactivity in six normal and 10 asthmatic subjects in a placebo controlled , crossover study . sGaw was measured before and up to 2 h after drug , followed by a histamine challenge test to estimate the dose of histamine causing a 35 % reduction in sGAW ( PD35 ) . sGAW values after ouabain and placebo did not differ significantly . Ouabain did not affect bronchial reactivity , geometric mean ( 95 % CI ) PD35 histamine values following ouabain and placebo were 8.98 ( 3.8 - 21.2 ) and 7.75 ( 3.2 - 18.7 ) mumol respectively in normal subjects and 0.46 ( 0.18 - 1.21 ) and 0.69 ( 0.22 - 2.13 ) in asthmatic subjects . We were thus unable to demonstrate a role for Na/K ATPase in determining bronchial reactivity to histamine in man To the Editor.— In the 19th century , cannabis products were commonly used in the treatment of asthma . 1 - 3 Smoking marihuana , on the other h and , is associated with bronchitis and other deleterious effects on lung function . 4 The present report deals with acute marihuana effects on pulmonary capacity in nonasthmatic regular marihuana smokers . Method .— Thirty-one healthy men between the ages of 21 and 30 years who had smoked marihuana frequently for at least two years were studied ; more than half had smoked marihuana at least once a week for four or more years . About half were cigarette smokers . None had current respiratory complaints or a history of pulmonary disease . Subjects were r and omly assigned to a marihuana group ( N = 15 ) or placebo group ( N = 16 ) . The marihuana contained 1.5 % tetrahydrocannabinol ( THC ) , while the placebo consisted of cannabis tobacco with THC removed . The National Institute of Mental Health provided the drug and the placebo |
13,804 | 26,436,959 | We found moderate- quality evidence that workplace interventions reduce time to first RTW , high- quality evidence that workplace interventions reduce cumulative duration of sickness absence , very low- quality evidence that workplace interventions reduce time to lasting RTW , and moderate- quality evidence that workplace interventions increase recurrences of sick leave .
Overall , the effectiveness of workplace interventions on work disability showed varying results .
Workplace interventions reduce time to RTW and improve pain and functional status in workers with musculoskeletal disorders .
We found no evidence of a considerable effect of workplace interventions on time to RTW in workers with mental health problems or cancer .
We found moderate- quality evidence to support workplace interventions for workers with musculoskeletal disorders .
The quality of the evidence on the effectiveness of workplace interventions for workers with mental health problems and cancer is low , and results do not show an effect of workplace interventions for these workers . | BACKGROUND Work disability has serious consequences for individuals as well as society .
It is possible to facilitate resumption of work by reducing barriers to return to work ( RTW ) and promoting collaboration with key stakeholders .
This review was first published in 2009 and has now been up date d to include studies published up to February 2015 .
OBJECTIVES To determine the effectiveness of workplace interventions in preventing work disability among sick-listed workers , when compared to usual care or clinical interventions . | Background To reduce the duration of sick leave and loss of productivity due to common mental disorders ( CMDs ) , we developed a return-to-work programme to be provided by occupational physicians ( OPs ) based on the principles of exposure in vivo ( RTW-E programme ) . This study evaluates this programme 's effectiveness and cost-effectiveness by comparing it with care as usual ( CAU ) . The three research questions we have are : 1 ) Is an RTW-E programme more effective in reducing the sick leave of employees with common mental disorders , compared with care as usual ? 2 ) Is an RTW-E programme more effective in reducing sick leave for employees with anxiety disorders compared with employees with other common mental disorders ? 3 ) From a societal perspective , is an RTW-E programme cost-effective compared with care as usual ? Methods / design This study was design ed as a pragmatic cluster-r and omized controlled trial with a one-year follow-up and r and omization on the level of OPs . We aim ed for 60 OPs in order to include 200 patients . Patients in the intervention group received the RTW-E programme . Patients in the control group received care as usual . Eligible patients had been on sick leave due to common mental disorders for at least two weeks and no longer than eight weeks . As primary outcome measures , we calculated the time until full return to work and the duration of sick leave . Secondary outcome measures were time until partial return to work , prevalence rate of sick leave at 3 , 6 , 9 , and 12 months ' follow-up , and scores of symptoms of distress , anxiety , depression , somatization , and fatigue ; work capacity ; perceived working conditions ; self-efficacy for return to work ; coping behaviour ; avoidance behaviour ; patient satisfaction ; and work adaptations . As process measures , we used indices of compliance with the intervention in the intervention group and employee-supervisor communication in both groups . Economic costs were calculated from a societal perspective . The total costs consisted of the costs of consuming health care , costs of production loss due to sick leave and reduced productivity , and out-of-pocket costs of patients for travelling to their OP . Discussion The results will be published in 2009 . The strengths and weaknesses of the study protocol are discussed . Trial registration IS RCT Background Considering the high costs of sick leave and the consequences of sick leave for employees , an early return-to-work of employees with mental disorders is very important . Therefore , a workplace intervention is developed based on a successful return-to-work intervention for employees with low back pain . The objective of this paper is to present the design of a r and omized controlled trial evaluating the cost-effectiveness of the workplace intervention compared with usual care for sick-listed employees with common mental disorders . Methods The study is design ed as a r and omized controlled trial with a follow-up of one year . Employees eligible for this study are on sick leave for 2 to 8 weeks with common mental disorders . The workplace intervention will be compared with usual care . The workplace intervention is a stepwise approach that aims to reach consensus about a return-to-work plan by active participation and strong commitment of both the sick-listed employee and the supervisor . Outcomes will be assessed at baseline , 3 , 6 , 9 and 12 months . The primary outcome of this study is lasting return-to-work , which will be acquired from continuous registration systems of the companies after the follow-up . Secondary outcomes are total number of days of sick leave during the follow-up , severity of common mental disorders , coping style , job content , and attitude , social influence , and self-efficacy determinants . Cost-effectiveness will be evaluated from the societal perspective . A process evaluation will also be conducted . Discussion Return-to-work is difficult to discuss in the workplace for sick-listed employees with mental disorders and their supervisors . Therefore , this intervention offers a unique opportunity for the sick-listed employee and the supervisor to discuss barriers for return-to-work . Results of this study will possibly contribute to improvement of disability management for sick-listed employees with common mental disorders . Results will become available in 2009.Trial registration IS RCT Background Musculoskeletal disorders ( MSDs ) are a major reason for impaired work productivity and sick leave . In 2009 , a national rehabilitation program was introduced in Sweden to promote work ability , and patients with MSDs were offered multimodal rehabilitation . The aim of this study was to analyse the effect of this program on health related quality of life , function , sick leave and work ability . Methods We conducted a prospect i ve , observational cohort study including 406 patients with MSDs attending multimodal rehabilitation . Changes over time and differences between groups were analysed concerning function , health related quality of life , work ability and sick leave . Regression analyses were used to study the outcome variables health related quality of life ( measured with EQ-5D ) , and sick leave . Results Functional ability and health related quality of life improved after rehabilitation . Patients with no sick leave/disability pension the year before rehabilitation , improved health related quality of life more than patients with sick leave/disability pension the year before rehabilitation ( p = 0.044 ) . During a period of −/+ four months from rehabilitation start , patients with EQ-5D ≥ 0.5 at rehabilitation start , reduced their net sick leave days with 0.5 days and patients with EQ-5D < 0.5 at rehabilitation start , increased net sick leave days with 1.5 days ( p = 0.019 ) . Factors negatively associated with sick leave at follow-up were earlier episodes of sick leave/disability pension , problems with exercise tolerance functions and mobility after rehabilitation . Higher age was associated with not being on sick leave at follow-up and reaching an EQ-5D ≥ 0.5 at follow-up . Severe pain after rehabilitation , problems with exercise tolerance functions , born outside of Sweden and full-time sick leave/disability pension the year before rehabilitation were all associated with an EQ-5D level < 0.5 at follow-up . Conclusions Patients with MSDs participating in a national work promoting rehabilitation program significantly improved their health related quality of life and functional ability , especially those with no sick leave . This shows that vocational rehabilitation programs in a primary health care setting are effective . The findings of this study can also be valuable for more appropriate patient selection for rehabilitation programs for MSDs Background Major depressive disorder is among the medical conditions with the highest negative impact on work outcome . However , little is known regarding evidence -based interventions targeting the improvement of work outcomes in depressed employees . In this paper , the design of a r and omized controlled trial is presented in order to evaluate the effectiveness of adjuvant occupational therapy in employees with depression . This occupational intervention is based on an earlier intervention , which was design ed and proven effective by our research group , and is the only intervention to date that specifically targets work outcome in depressed employees . Methods / Design In a two-arm r and omized controlled trial , a total of 117 participants are r and omized to either ' care as usual ' or ' care as usual ' with the addition of occupational therapy . Patients included in the study are employees who are absent from work due to depression for at least 25 % of their contract hours , and who have a possibility of returning to their own or a new job . The occupational intervention consists of six individual sessions , eight group sessions and a work-place visit over a 16-week period . By increasing exposure to the working environment , and by stimulating communication between employer and employee , the occupational intervention aims to enhance self-efficacy and the acquisition of more adaptive coping strategies . Assessment s take place at baseline , and at 6 , 12 , and 18-month follow-ups . Primary outcome measure is work participation ( hours of absenteeism and time until work resumption ) . Secondary outcome measures are work functioning , symptomatology , health-related quality of life , and neurocognitive functioning . In addition , cost-effectiveness is evaluated from a societal perspective . Finally , mechanisms of change ( intermediate outcomes ) and potential patient-treatment matching variables are investigated . Discussion This study hopes to provide valuable knowledge regarding an intervention to treat depression , one of the most common and debilitating diseases of our time . If our intervention is proven ( cost- ) effective , the personal , economic , and health benefits for both patients and employers are far-reaching . Trial registration R and omised controlled trial to evaluate the effectiveness of collaborative care in a Dutch occupational healthcare setting : 126 workers on sick leave with major depressive disorder were r and omised to usual care ( n = 61 ) or collaborative care ( n = 65 ) . After 3 months , collaborative care was more effective on the primary outcome measure of treatment response ( i.e. reduction in symptoms of ≥50 % ) on the Patient Health Question naire-9 ( PHQ-9 ) . However , the groups did not differ on the PHQ-9 as a continuous outcome measure . Implication s of these results are discussed Background There is a paucity of method ologically robust vocational rehabilitation ( VR ) intervention trials . This study assessed the feasibility and acceptability of a VR trial of women with breast cancer to inform the development of a larger interventional study . Methods Women were recruited in Scotl and and r and omised to either a case management VR service or to usual care . Data were collected on eligibility , recruitment and attrition rates to assess trial feasibility , and interviews conducted to determine trial acceptability . Sick leave days ( primary outcome ) were self-reported via postal question naire every 4 weeks during the first 6 months post-surgery and at 12 months . Secondary outcome measures were change in employment pattern , quality of life and fatigue . Results Of the 1,114 women assessed for eligibility , 163 ( 15 % ) were eligible . The main reason for in eligibility was age ( > 65 years , n = 637 , 67 % ) . Of those eligible , 111 ( 68 % ) received study information , of which 23 ( 21 % ) consented to participate in the study . Data for 18 ( 78 % ) women were analysed ( intervention : n = 7 ; control : n = 11 ) . Participants in the intervention group reported , on average , 53 fewer days of sick leave over the first 6 months post-surgery than those in the control group ; however , this difference was not statistically significant ( p = 0.122 ; 95 % confidence interval −15.8 , 122.0 ) . No statistically significant differences were found for secondary outcomes . Interviews with trial participants indicated that trial procedures , including recruitment , r and omisation and research instruments , were acceptable . Conclusions Conducting a pragmatic trial of effectiveness of a VR intervention among cancer survivors is both feasible and acceptable , but more research about the exact components of a VR intervention and choice of outcomes to measure effectiveness is required . VR to assist breast cancer patients in the return to work process is an important component of cancer survivorship plans . Trial registration IS RCT Purpose . Test the feasibility and impact of an automated workplace mental health assessment and intervention . Design . Efficacy was evaluated in a r and omized control trial comparing employees who received screening and intervention with those who received only screening . Setting . Workplace . Subjects . 463 volunteers from Boston Medical Center , Boston University , and EMC and other employed adults , among whom 164 were r and omized to the intervention ( N = 87 ) and control ( N = 77 ) groups . Intervention . The system administers a panel of telephonic assessment instruments followed by tailored information , education , and referrals . Measures . The Work Limitation Question naire , the Medical Outcomes Question naire Short Form-12 , the Patient Health Question naire-9 , question 10 from the Patient Health Question naire to measure functional impairment , and the Perceived Stress Scale-4 and questions written by study psychiatrists to measure emotional distress and social support respectively . The WHO-Five Well-being Index was administered to measure overall well-being . Analysis . Independent sample t-tests and χ2 tests as well as mean change were used to compare the data . Results . No significant differences on 16 of the 20 comparisons at 3- and 6-month time points . The intervention group showed a significant improvement in depression ( p ≤ .05 ) at 3 months and on two Work Limitation Question naire subscales , the Mental-Interpersonal Scale ( p ≤ .05 ) and the Time and Scheduling Scale ( p ≤ .05 ) , at 3 and 6 months respectively with a suggestive improvement in mental health at 6 months ( p ≤ .10 ) . Conclusions . This is a potentially fruitful area for research with important implication s for workplace behavioral interventions . ( Am J Health Promot 2011;25[3]:207–216 . Background To describe the design of a population based r and omized controlled trial ( RCT ) , including a cost-effectiveness analysis , comparing participative ergonomics interventions between 2–8 weeks of sick leave and Grade d Activity after 8 weeks of sick leave with usual care , in occupational back pain management . Methods Design : An RCT and cost-effectiveness evaluation in employees sick-listed for a period of 2 to 6 weeks due to low back pain . Interventions used are 1 . Communication between general practitioner and occupational physician plus Participative Ergonomics protocol performed by an ergonomist . 2 . Grade d Activity based on cognitive behavioural principles by a physiotherapist . 3 . Usual care , provided by an occupational physician according to the Dutch guidelines for the occupational health management of workers with low back pain . The primary outcome measure is return to work . Secondary outcome measures are pain intensity , functional status and general improvement . Intermediate variables are kinesiophobia and pain coping . The cost-effectiveness analysis includes the direct and indirect costs due to low back pain . The outcome measures are assessed before r and omization ( after 2–6 weeks on sick leave ) and 12 weeks , 26 weeks and 52 weeks after first day of sick leave . Discussion The combination of these interventions has been subject of earlier research in Canada . The results of the current RCT will : 1 . crossvali date the Canadian findings in an different sociocultural environment ; 2 . add to the cost-effectiveness on treatment options for workers in the sub acute phase of low back pain . Results might lead to alterations of existing (inter)national guidelines Purpose Underst and ing individual factors associated with return to work ( RTW ) post-injury is an important goal of compensation systems research . The aim of the present study was to determine factors associated with time to return to work following acute unintentional injuries . Methods A prospect i ve cohort study was conducted in Victoria , Australia . The cohort comprised 133 persons who were employed at the time they were admitted to one of three study hospitals . Baseline health status data was obtained retrospectively at one-week post-injury and participants were further surveyed at 1 , 6 , 12 , 26 and 52 weeks post-injury to measure recovery . Multivariate Cox proportional hazards regression analysis was used to examine the association between potential prognostic factors and time to RTW during the 12 month study . Results At the end of 12 months follow-up , 81.2 % of the study cohort had returned to work . Older age , increased injury severity , self reported symptomatic pain and poor mental health at 1 week post-injury were associated with extended time to RTW . A significant statistical interaction between the receipt of compensation and high social functioning as measured by the SF-36 or strong social relationships as measured by the Assessment of Quality of Life was associated with earlier RTW . Participants reporting strong social relationships and high social functioning at 1 week post-injury and entitled to injury compensation returned to work 2.05 and 3.66 times earlier respectively , than similar participants with no entitlement to compensation . Conclusions Both injury-related and psychosocial factors were associated with the duration of time to RTW following acute unintentional injuries . This study replicated previously reported findings on social functioning and compensation from an independent acute trauma sample . Programs or policies to improve social functioning early post-injury may provide opportunities to improve the duration of time to RTW following injury Objective To evaluate the effectiveness of an integrated care programme , combining a patient directed and a workplace directed intervention , for patients with chronic low back pain . Design Population based r and omised controlled trial . Setting Primary care ( 10 physiotherapy practice s , one occupational health service , one occupational therapy practice ) and secondary care ( five hospitals ) . Participants 134 adults aged 18 - 65 sick listed for at least 12 weeks owing to low back pain . Intervention Patients were r and omly assigned to usual care ( n=68 ) or integrated care ( n=66 ) . Integrated care consisted of a workplace intervention based on participatory ergonomics , involving a supervisor , and a grade d activity programme based on cognitive behavioural principles . Main outcome measures The primary outcome was the duration of time off work ( work disability ) due to low back pain until full sustainable return to work . Secondary outcome measures were intensity of pain and functional status . Results The median duration until sustainable return to work was 88 days in the integrated care group compared with 208 days in the usual care group ( P=0.003 ) . Integrated care was effective on return to work ( hazard ratio 1.9 , 95 % confidence interval 1.2 to 2.8 , P=0.004 ) . After 12 months , patients in the integrated care group improved significantly more on functional status compared with patients in the usual care group ( P=0.01 ) . Improvement of pain between the groups did not differ significantly . Conclusion The integrated care programme substantially reduced disability due to chronic low back pain in private and working life . Trial registration Current Controlled Trials IS RCT N28478651 Study Design . R and omized controlled trial . Objectives . To investigate the effectiveness and costs of a mini-intervention , provided in addition to the usual care , and the incremental effect of a work site visit for patients with subacute disabling low back pain . Summary of Background Data . There is lack of data on cost-effectiveness of brief interventions for patients with prolonged low back pain . Methods . A total of 164 patients with subacute low back pain were r and omized to a mini-intervention group ( A ) , a work site visit group ( B ) , or a usual care group ( C ) . Groups A ( n = 56 ) and B ( n = 51 ) underwent one assessment by a physician plus a physiotherapist . Group B received a work site visit in addition . Group C served as controls ( n = 57 ) and was treated in municipal primary health care . All patients received a leaflet on back pain . Pain , disability , specific and generic health-related quality of life , satisfaction with care , days on sick leave , and use and costs of health care consumption were measured at 3- , 6- , and 12-month follow-ups . Results . During follow-up , fewer subjects had daily pain in Groups A and B than in Group C ( Group A vs. Group C , P = 0.002 ; Group B vs. Group C , P = 0.030 ) . In Group A , pain was less bothersome ( Group A vs. Group C , P = 0.032 ) and interfered less with daily life ( Group A vs. Group C , P = 0.040 ) than among controls . Average days on sick leave were 19 in Group A , 28 in Group B , and 41 in Group C ( Group A vs. Group C , P = 0.019 ) . Treatment satisfaction was better in the intervention groups than among the controls , and costs were lowest in the mini-intervention group . Conclusions . Mini-intervention reduced daily back pain symptoms and sickness absence , improved adaptation to pain and patient satisfaction among patients with subacute low back pain , without increasing health care costs . A work site visit did not increase effectiveness Background Major depressive disorder ( MDD ) has major consequences for both patients and society , particularly in terms of needlessly long sick leave and reduced functioning . Although evidence -based treatments for MDD are available , they show disappointing results when implemented in daily practice . A focus on work is also lacking in the treatment of depressive disorder as well as communication of general practitioners ( GPs ) and other health care professionals with occupational physicians ( OPs ) . The OP may play a more important role in the recovery of patients with MDD . Purpose of the present study is to tackle these obstacles by applying a collaborative care model , which has proven to be effective in the USA , with a focus on return to work ( RTW ) . From a societal perspective , the (cost)effectiveness of this collaborative care treatment , as a way of transmural care , will be evaluated in depressed patients on sick leave in the occupational health setting . Methods / Design A r and omised controlled trial in which the treatment of MDD in the occupational health setting will be evaluated in the Netherl and s. A transmural collaborative care model , including Problem Solving Treatment ( PST ) , a workplace intervention , antidepressant medication and manual guided self-help will be compared with care as usual ( CAU ) . 126 Patients with MDD on sick leave between 4 and 12 weeks will be included in the study . Care in the intervention group will be provided by a multidisciplinary team of a trained OP-care manager and a consultant psychiatrist . The treatment is separated from the sickness certification . Data will be collected by means of question naires at baseline and at 3 , 6 , 9 and 12 months after baseline . Primary outcome measure is reduction of depressive symptoms , secondary outcome measure is time to RTW , tertiary outcome measure is the cost effectiveness . Discussion The high burden of MDD and the high level of sickness absence among people with MDD contribute to the relevance of this study . The intervention is an innovative approach , with trained OPs in a new role as care managers in the treatment of MDD . If this intervention proves to be cost-effective , implementation will be very relevant for individual patients as well as for society . Trial registration IS RCT Introduction Within the labour force workers without an employment contract represent a vulnerable group . In most cases , when sick-listed , these workers have no workplace/employer to return to . Therefore , the aim of this study was to evaluate the effectiveness on return-to-work of a participatory return-to-work program compared to usual care for unemployed workers and temporary agency workers , sick-listed due to musculoskeletal disorders . Methods The workers , sick-listed for 2–8 weeks due to musculoskeletal disorders , were r and omly allocated to the participatory return-to-work program ( n = 79 ) or to usual care ( n = 84 ) . The new program is a stepwise procedure aim ed at making a consensus-based return-to-work plan , with the possibility of a temporary ( therapeutic ) workplace . Outcomes were measured at baseline , 3 , 6 , 9 and 12 months . The primary outcome measure was time to sustainable first return-to-work . Secondary outcome measures were duration of sickness benefit , functional status , pain intensity , and perceived health . Results The median duration until sustainable first return-to-work was 161 days in the intervention group , compared to 299 days in the usual care group . The new return-to-work program result ed in a non-significant delay in RTW during the first 90 days , followed by a significant advantage in RTW rate after 90 days ( hazard ratio of 2.24 [ 95 % confidence interval 1.28–3.94 ] P = 0.005 ) . No significant differences were found for the measured secondary outcomes . Conclusions The newly developed participatory return-to-work program seems to be a promising intervention to facilitate work resumption and reduce work disability among temporary agency workers and unemployed workers , sick-listed due to musculoskeletal disorders CONTEXT Selective reporting of outcomes within published studies based on the nature or direction of their results has been widely suspected , but direct evidence of such bias is currently limited to case reports . OBJECTIVE To study empirically the extent and nature of outcome reporting bias in a cohort of r and omized trials . DESIGN Cohort study using protocol s and published reports of r and omized trials approved by the Scientific-Ethical Committees for Copenhagen and Frederiksberg , Denmark , in 1994 - 1995 . The number and characteristics of reported and unreported trial outcomes were recorded from protocol s , journal articles , and a survey of trialists . An outcome was considered incompletely reported if insufficient data were presented in the published articles for meta- analysis . Odds ratios relating the completeness of outcome reporting to statistical significance were calculated for each trial and then pooled to provide an overall estimate of bias . Protocol s and published articles were also compared to identify discrepancies in primary outcomes . MAIN OUTCOME MEASURES Completeness of reporting of efficacy and harm outcomes and of statistically significant vs nonsignificant outcomes ; consistency between primary outcomes defined in the most recent protocol s and those defined in published articles . RESULTS One hundred two trials with 122 published journal articles and 3736 outcomes were identified . Overall , 50 % of efficacy and 65 % of harm outcomes per trial were incompletely reported . Statistically significant outcomes had a higher odds of being fully reported compared with nonsignificant outcomes for both efficacy ( pooled odds ratio , 2.4 ; 95 % confidence interval [ CI ] , 1.4 - 4.0 ) and harm ( pooled odds ratio , 4.7 ; 95 % CI , 1.8 - 12.0 ) data . In comparing published articles with protocol s , 62 % of trials had at least 1 primary outcome that was changed , introduced , or omitted . Eighty-six percent of survey responders ( 42/49 ) denied the existence of unreported outcomes despite clear evidence to the contrary . CONCLUSIONS The reporting of trial outcomes is not only frequently incomplete but also biased and inconsistent with protocol s. Published articles , as well as review s that incorporate them , may therefore be unreliable and overestimate the benefits of an intervention . To ensure transparency , planned trials should be registered and protocol s should be made publicly available prior to trial completion Background Compared to healthy controls , cancer patients have a higher risk of unemployment , which has negative social and economic impacts on the patients and on society at large . Therefore , return-to-work of cancer patients needs to be improved by way of an intervention . The objective is to describe the development and content of a work-directed intervention to enhance return-to-work in cancer patients and to explain the study design used for evaluating the effectiveness of the intervention . Development and content of the interventionThe work-directed intervention has been developed based on a systematic literature review of work-directed interventions for cancer patients , factors reported by cancer survivors as helping or hindering their return-to-work , focus group and interview data for cancer patients , health care professionals , and supervisors , and vocational rehabilitation literature . The work-directed intervention consists of : 1 ) 4 meetings with a nurse at the treating hospital department to start early vocational rehabilitation , 2 ) 1 meeting with the participant , occupational physician , and supervisor to make a return-to-work plan , and 3 ) letters from the treating physician to the occupational physician to enhance communication . Study design to evaluate the interventionThe treating physician or nurse recruits patients before the start of initial treatment . Patients are eligible when they have a primary diagnosis of cancer , will be treated with curative intent , are employed at the time of diagnosis , are on sick leave , and are between 18 and 60 years old . After the patients have given informed consent and have filled out a baseline question naire , they are r and omised to either the control group or to the intervention group and receive either care as usual or the work-directed intervention , respectively . Primary outcomes are return-to-work and quality of life . The feasibility of the intervention and direct and indirect costs will be determined . Outcomes will be assessed by a question naire at baseline and at 6 , 12 , 18 , and 24 months after baseline . Discussion This study will provide information about the effectiveness of a work-directed intervention for cancer patients . The intention is to implement the intervention in normal care if it has been shown effective . Trial registration Background Common mental disorders ( CMD ) have a major impact on both society and individual workers , so return to work ( RTW ) is an important issue . In The Netherl and s , the occupational physician plays a central role in the guidance of sick-listed workers with respect to RTW . Evidence -based guidelines are available , but seem not to be effective in improving RTW in people with CMD . An intervention supporting the occupational physician in guidance of sick-listed workers combined with specific guidance regarding RTW is needed . A blended E-health module embedded in collaborative occupational health care is now available , and comprises a decision aid supporting the occupational physician and an E-health module , Return@Work , to support sick-listed workers in the RTW process . The cost-effectiveness of this intervention will be evaluated in this study and compared with that of care as usual . Methods This study is a two-armed cluster r and omized controlled trial , with r and omization done at the level of occupational physicians . Two hundred workers with CMD on sickness absence for 4–26 weeks will be included in the study . Workers whose occupational physician is allocated to the intervention group will receive the collaborative occupational health care intervention . Occupational physicians allocated to the care as usual group will give conventional sickness guidance . Follow-up assessment s will be done at 3 , 6 , 9 , and 12 months after baseline . The primary outcome is duration until RTW . The secondary outcome is severity of symptoms of CMD . An economic evaluation will be performed as part of this trial . Conclusion It is hypothesized that collaborative occupational health care intervention will be more (cost)-effective than care as usual . This intervention is innovative in its combination of a decision aid by email sent to the occupational physician and an E-health module aim ed at RTW for the sick-listed worker OBJECTIVES : To assess if the implementation of guidelines for occupational rehabilitation of patients with low back pain by means of process variables -- a set of objective criteria for technical performance and continuity of care -- led to a better outcome in clinical and return to work variables . METHODS : The study group consisted of 59 patients with at least 10 days of sick leave because of low back pain . Univariate analyses as well as multiple logistic regression and Cox 's regression analyses were performed to assess the relation between quality of care and outcome . RESULTS : Process indicators for technical competence , continuity of care , and total performance were all significantly related to satisfaction of employees . Continuity of care and total performance were significantly related to working status at 3 months , and time to return to work . None of the process indicators was related to pain or disability after 3 months follow up . Satisfaction was not related to any of the other outcome variables . This indicates that if guidelines for occupational rehabilitation are met , outcome is better . CONCLUSION : Quality of the process of care was related to outcome . Interventions of occupational physicians need improvement in the areas of continuity of care and communication with treating physicians . The effectiveness of an improved intervention should be studied in a subsequent r and omised clinical trial As the Nation 's first rigorous large-scale evaluation of vocational rehabilitation ( VR ) assistance to persons with severe disabilities , the Project NetWork demonstration will provide a wide range of information to policy-makers , research ers , and other interest groups . The evaluation of Project NetWork addresses two key policy questions : Is it feasible to increase participation in VR services among Disability Insurance ( DI ) beneficiaries and Supplemental Security Income ( SSI ) applicants/recipients through a combination of intensive outreach , case management , and enhanced work incentives ? Do the interventions tested produce net benefits from the perspective of participants , society , the DI Trust Fund , and the Federal Government , as a whole ? The study utilizes a r and omized field experiment design to evaluate the net impact of the demonstration on participant employment , earnings , receipt of transfer benefits , social and psychological well-being , and other variables of interest to policymakers . A combination of SSA administrative data , information from the demonstration 's onsite management information system ( MIS ) , and in-person interviews ( containing a rich array of information on disability , health , and attitudes ) supports the evaluation . This article summarizes three aspects of the evaluation : Its experimental and sample design ; the methods and data to be used to analyze project benefits , costs , and participation ; and the challenges faced during demonstration implementation . It also presents preliminary data on the characteristics of Project NetWork participants and eligibles OBJECTIVE To investigate the outcome of a brief vocational-oriented intervention aim ing to motivate disability pensioners with back pain to return to work , and to evaluate prognostic factors for having entered a return to work process during the following year . DESIGN A r and omized controlled trial was conducted . SUBJECTS Participants ( n = 89 ) ( mean age 49 years , 65 % women ) who had received disability pension for more than one year were r and omized into an intervention group ( education , reassurance , motivation , vocational counselling , n = 45 ) and a control group ( n = 44 ) . METHODS Primary outcome measures were return to work or having entered a return to work process . Secondary outcome measures were life satisfaction , disability , fear avoidance behaviour and expectancy . RESULTS The intervention had no statistically significant effect on return to work or having entered a return to work process at 1-year follow-up . Twice as many in the intervention group ( n = 10 , 22 % ) had entered a return to work process compared with the controls ( n = 5 , 11 % ) . The number needed to treat was 9.2 ( 95 % confidence interval ( CI ) = 3.4 , Inf ) . Only minor differences in secondary outcome measures were demonstrated . Positive expectancy , better physical performance and less pain were related to return to work . CONCLUSION The effort of returning disability pensioners to work by a brief vocational-oriented intervention may be of clinical relevance . The effect needs to be explored further in larger sample s of disability pensioners This paper describes a participatory ergonomics program aim ed at early return to regular work of workers suffering from subacute occupational back pain and assesses the perceptions of the participants on the implementation of ergonomic solutions in the workplace . The participatory ergonomics program was used in the rehabilitation of workers suffering from subacute back pain for more than 6 weeks , a program that was associated with an increased rate of return to work . The perceptions of the participatory ergonomics participants were assessed 6 months after completion of the ergonomic intervention through a question naire sent to employer representatives , union representatives and injured workers of participating workplaces . About half of the ergonomic solutions were implemented according to the perception of the participants , with a substantial agreement between respondents Study Design . Population ‐based r and omized clinical trial . Objectives . To develop and test a model of management of subacute back pain , to prevent prolonged disability . Summary of Background Data . The present management of back pain seems inadequate , and development of innovative models has been urged . Methods . A model for the treatment of subacute work‐related back pain has been developed and evaluated in a population ‐based r and omized clinical trial . Workers ( n = 130 ) from eligible workplaces in the Sherbrooke area ( N = 31 ) , who had been absent from work for more than 4 weeks for back pain , were r and omized , based on their workplace , in one of four treatment groups : usual care , clinical intervention , occupational intervention , and full intervention ( a combination of the last two ) . The duration of absence from regular work and from any work was evaluated using survival analysis . Functional status and pain were compared at study entry and after 1 year of follow‐up . Results . The full intervention group returned to regular work 2.41 times faster than the usual care intervention group ( 95 % confidence interval 1.19‐4.89 ; P = 0.01 ) . The specific effect of the occupational intervention accounted for the most important part of this result , with a rate ratio of return to regular work of 1.91 ( 95 % confidence interval = 1.18‐3.10 ; P < 0.01 ) . Pain and disability scales demonstrated either a statistically significant reduction or a trend toward reduction in the three intervention groups , compared with the trend in the usual care intervention group . Conclusions . Close association of occupational intervention with clinical care is of primary importance in impeding progression toward chronicity of low back pain Introduction Return to work following an occupational injury is a multifactoral process although many traditional clinic-based rehabilitation programs do not appreciate the importance of workplace factors . A r and omized controlled trial was conducted to investigate the effect of workplace-based rehabilitation program on the return to work outcome of work-related rotator cuff disorder , which is based on the therapeutic use of actual work facilities and work environment . Methods A total of 103 workers were recruited and r and omly assigned into Clinic-based Work Hardening ( CWH ) or Workplace-based Work Hardening ( WWH ) groups . The CWH group were given traditional generic work hardening training while WWH group received workplace-based work hardening training with rehabilitative principles of athletic rotator cuff pathology , biomechanics and specific job activities . Results After four weeks , a higher return to work rate was obtained in WWH group compared to CWH group ( 71.4 % vs. 37 % , p < 0.01 ) . A statistically significant difference ( p < 0.05 ) was also noted in lowering of self-reported shoulder problems and functional work capabilities in the WWH group versus the CWH group . Conclusion Workplace-based rehabilitation program appeared to be more effective in facilitating the return to work process of the injured worker as assessed immediately following intervention . In particular this approached was associated with many of the psychosocial workplace factors related to separation from the work routine . The influence of peer group and /or employer could be minimized . This initial attempt with rotator cuff injuries appears promising however long-term outcome needs to be determined OBJECTIVES In case of long-term sick leave , gradually increasing workload appears to be an effective component of work-directed interventions to reduce sick leave due to common mental disorders ( CMD ) . CMD are defined as stress-related , adjustment , anxiety , or depressive disorders . We developed an exposure-based return-to-work ( RTW-E ) intervention and evaluated the effect on time-to-full return to work ( RTW ) among workers who were on sick leave due to CMD in comparison to those treated with care-as-usual ( CAU ) . CAU is guideline -directed and consists of problem-solving strategies and grade d activities . METHODS Using a two-armed cluster-r and omized trial , we r and omized 56 occupational physicians ( OP ) . Of these , 35 OP treated 160 workers at the start of their sick leave ; 75 workers received RTW-E and 85 workers received CAU . These workers were followed over a 12-month follow-up period . The time-to-full RTW lasting ≥28 days without recurrence was the primary outcome measure . To evaluate differences between groups , we used intention-to-treat and multilevel Cox 's regression analysis . RESULTS The median time-to-full RTW differed significantly between groups [ hazard ratio ( HR ) 0.55 ; 95 % confidence interval ( 95 % CI ) 0.33 - 0.89 ] . The workers receiving RTW-E ( 209 days ; 95 % CI 62 - 256 ) had a prolonged time-to-full RTW compared to workers receiving CAU ( 153 days ; 95 % CI 128 - 178 ) . CONCLUSIONS Workers on sick leave due to CMD treated with RTW-E showed a prolonged time-to-full RTW compared to those treated with CAU . We recommend that OP do not apply RTW-E but continue counseling workers on sick leave due to CMD according to CAU Background Long-term sick leave has been of concern to politicians and decision-makers in Norway for several years . In the current study we assess the feasibility and effectiveness of offering a voluntary , solution-focused follow-up to sick-listed employees . Methods Employees on long-term sick leave due to psychological problems or muscle skeletal pain were r and omly allocated to be offered a solution-focused follow-up ( n = 122 ) or " treatment as usual " ( n = 106 ) . The intervention was integrated within 2 social security offices ' regular follow-up . The intervention group was informed about the offer with letters , telephone calls and information meetings . Feasibility was measured by rate of uptake to the intervention , and effectiveness by number of days on sick leave . Results In general , few were reached with the different information elements . While the letter was sent to all , only 31 % were reached by telephone and 15 % attended the information meetings . Thirteen employees ( 11.5 % ) in the intervention group participated in the solution-focused follow-up . Intention to treat analysis showed no difference in mean length of sick leave between the intervention group ( 217 days ) and the control group ( 189 days ) ( p = 0,101 ) . Conclusion Even if the information strategy might be improved , it is not likely that a voluntary solution-focused follow-up offered by the social security offices would result in measurable reduction in length of sick leave on a population level . However , the efficacy of a solution-focused follow-up for the persons reporting a need for this approach should be further investigated Study Design . R and omized parallel-group comparative trial with a 6-month follow-up period . Objective . To compare , in chronic low back pain patients , the effectiveness of a functional restoration program , including intensive physical training , occupational therapy , and psychological support to an active individual therapy consisting of 3 hours physical therapy per week during 5 weeks . Summary of Background Data . Controlled studies conducted in the United States showed a benefit of functional restoration in patients with low back pain , especially on return to work . R and omized Canadian and European trials had less favorable results . In France , there has been up to now no r and omized study . Controlled studies suggested a positive effect of functional restoration programs . Methods . Eighty-six patients with low back pain were r and omized to either the functional restoration ( 44 patients ) or the active individual therapy ( 42 patients ) program . One person in each group never started the program . Two patients did not complete the functional restoration program , and one was lost to follow-up at 6 months . The mean number of sick-leave days in the 2 previous years was 6 months . Results . After adjustment on the variable ≪ workplace enrolled in an ergonomic program ≫ , the mean number of sick-leave days was significantly lower in the functional restoration group . Physical criteria and treatment appreciation were also better . There was no significant difference in the intensity of pain , the quality of life and functional indexes , the psychological characteristics , the number of contacts with the medical system , and the drug intake . Conclusions . This study demonstrates the effectiveness of a functional restoration program on important outcome measures , such as sick leave , in a country that has a social system that protects people facing difficultiesat work Purpose Major depression is associated with high levels of absence and reduced productivity . Therefore the costs to society are high . The aim of this study was to evaluate the cost-utility of collaborative care for major depressive disorder ( MDD ) compared to care as usual in an occupational healthcare setting . A societal perspective was taken . Methods In this r and omised controlled trial , 126 sick-listed workers with MDD were included ( 65 collaborative care , 61 care as usual ) . Baseline measurements and follow up measures ( 3 , 6 , 9 and 12 months ) were assessed by question naire . We applied the Trimbos/iMTA question naire for costs associated with psychiatric illness , the SF-HQL and the EQ-5D respectively measuring the health care utilization , production losses and general health related quality of life . Results The average annual healthcare costs in the collaborative care group were € 3,874 ( 95 % CI € 2,778–€5,718 ) compared to € 4,583 ( 95 % CI € 3,108–€6,794 ) in the care as usual group . The average quality of life years ( QALY ’s ) gained were lower in the collaborative care group , 0.05 QALY . The majority of the ICERS ( 69 % ) indicate that collaborative care is less costly but also less effective than care as usual . Including the productivity costs did not change this result . Conclusions The cost-utility analysis showed that collaborative care generated reduced costs and a reduction in effects compared to care as usual and was therefore not a cost-effective intervention Background Long-term sick leave has been of concern to politicians and decision-makers in Norway for several years . In the current study we assess the efficacy of a solution-focused follow-up for sick-listed employees . Methods Employees on long-term sick leave due to psychological problems or muscle skeletal pain ( n = 703 ) were invited to participate in the project . Following self-recruitment , 103 were r and omly allocated to receive solution-focused follow-up ( n = 53 ) or " treatment as usual " ( n = 50 ) . The intervention was integrated within the regular follow up of six social security offices and organised as eight weekly solution focused work sessions . Effectiveness was measured by rate of return to work and health related quality of life ( SF-36 ) . Results Intention to treat analysis showed no significant differences between the two groups for any of the outcome measures . Secondary analysis , comparing those who attended at least 50 % of the sessions with the control group revealed a significant difference in favour of the active intervention group in the SF-36 subscale of mental health ( Effect Size 0.56 , p = 0.05 ) . When comparing the subgroup of participants with psychological problems there was a significant difference in mental health in favour of the intervention group ( Effect Size 0.71 , p = 0.041 ) . Conclusion A voluntary solution-focused intervention offered by social-security offices is no more effective than regular follow up for employees on long-term sick leave due to psychological problems or muscle skeletal pain Objectives To evaluate the cost effectiveness , cost utility and cost benefit of a workplace intervention compared with usual care for sick-listed employees with distress . Methods An economic evaluation was conducted alongside a r and omised controlled trial . Employees with distress and who were sick-listed for 2–8 weeks were r and omised to a workplace intervention ( n=73 ) or to usual care ( n=72 ) . The workplace intervention is a stepwise process involving the sick-listed employee and their supervisor , aim ed at formulating a consensus-based plan for return to work ( RTW ) . The effect outcomes were lasting RTW and quality -adjusted life years ( QALYs ) . Healthcare utilisation was measured over 12 months . Cost effectiveness analyses ( CEA ) and cost utility analyses ( CUA ) were conducted from the societal perspective and cost benefit analyses ( CBA ) from the employer perspective . Bootstrapping techniques were used to estimate cost and effect differences , related CIs , and cost effectiveness and cost utility ratios . Cost effectiveness planes were presented and subgroup analyses were performed . Results CEA and CUA revealed no statistically significant differences in lasting RTW , QALYs or costs . The CBA indicated a statistically significant higher cost of occupational health services in the workplace intervention group . The workplace intervention was not cost effective according to the CEA , CUA and CBA . Conclusions Widespread implementation of the workplace intervention for sick-listed employees with distress is not recommended because there was no economic benefit compared with usual care . Future trials should confirm if the workplace intervention is cost effective for the subgroup employees who intended to return to work despite symptoms . This trial has been registered at the Dutch National Trial Register IS RCT N92307123 OBJECTIVE Goal setting and motivational factors are strongly associated with maintaining a job and return to work after sick leave , but research into the effects of interventions targeting these factors is limited . We conducted a r and omized controlled study to examine the vocational effect of intervention focusing on motivation , goal setting and planning for return to work . DESIGN AND METHODS Of 243 patients at risk of long-term sick leave or job dropout , 184 ( 76 % ) provided complete baseline information for the study . After r and omization to an intervention group ( n=92 ) and a reference group ( n=92 ) , occupational physicians examined the participants in accordance with st and ard guidelines . The intervention group received additional support from a social worker in order to enhance goal setting , motivation and planning for return to work . After 1 year 163 participants ( 89 % ) provided data on general health and employment status . The risk of not being gainfully employed was analysed by logistic regression analysis with adjustment for several covariates . RESULTS The intervention did not increase the likelihood of gainful employment after 1 year or reduce the average number of days of sick leave . CONCLUSION A low-cost counselling program addressing motivation , goal setting and planning for return to work did not improve vocational outcomes or reduce sick leave among patients with work-related disorders Objective One key aspect of cancer survivorship is return-to-work . Unfortunately , many cancer survivors face problems upon their return-to-work . For that reason , we developed a hospital-based work support intervention aim ed at enhancing return-to-work . We studied effectiveness of the intervention compared to usual care for female cancer patients in a multi-centre r and omised controlled trial . Methods Breast and gynaecological cancer patients who were treated with curative intent and had paid work were r and omised to the intervention group ( n = 65 ) or control group ( n = 68 ) . The intervention involved patient education and support at the hospital and improvement of communication between treating and occupational physicians . In addition , we asked patient 's occupational physician to organise a meeting with the patient and the supervisor to make a concrete gradual return-to-work plan . Outcomes at 12 months of follow-up included rate and time until return-to-work ( full or partial ) , quality of life , work ability , work functioning , and lost productivity costs . Time until return-to-work was analyzed with Kaplan-Meier survival analysis . Results Return-to-work rates were 86 % and 83 % ( p = 0.6 ) for the intervention group and control group when excluding 8 patients who died or with a life expectancy of months at follow-up . Median time from initial sick leave to partial return-to-work was 194 days ( range 14–435 ) versus 192 days ( range 82–465 ) ( p = 0.90 ) with a hazard ratio of 1.03 ( 95 % CI 0.64–1.6 ) . Quality of life and work ability improved statistically over time but did not differ statistically between groups . Work functioning and costs did not differ statistically between groups . Conclusion The intervention was easily implemented into usual psycho-oncological care and showed high return-to-work rates . We failed to show any differences between groups on return-to-work outcomes and quality of life scores . Further research is needed to study which aspects of the intervention are useful and which elements need improvement . Trial Registration Nederl and s Trial Register ( NTR ) Background Brief intervention programs are clinical ly beneficial , and cost efficient treatments for low back pain , when offered at 8 - 12 weeks , compared with treatment as usual . However , about 30 % of the patients do not return to work . The European Guidelines for treatment of chronic low back pain recommends Cognitive Behavioral Therapy ( CBT ) , but conclude that further research is needed to evaluate the effectiveness of CBT for chronic low back pain . Methods / Design The aim of the multicenter CINS trial ( Cognitive Interventions and Nutritional Supplements ) is to compare the effectiveness of 4 different interventions ; Brief Intervention , Brief Intervention and CBT , Brief Intervention and nutritional supplements of seal oil , and Brief Intervention and nutritional supplements of soy oil . All participants will be r and omly assigned to the interventions . The nutritional supplements will be tested in a double blind design . 400 patients will be recruited from a population of chronic low back pain patients that have been sick listed for 2 - 10 months . Four outpatient clinics , located in different parts of Norway , will participate in recruitment and treatment of the patients .The Brief Intervention is a one session cognitive , clinical examination program based on a non-injury model , where return to normal activity and work is the main goal , and is followed by two booster sessions . The CBT is a tailored treatment involving 7 sessions , following a detailed manual . The nutritional supplements consist of a dosage of 10 grams of either soy or seal oil ( capsules ) per day for 3 months , administered in a double blind design . All patients will be followed up with question naires after 3 , 6 and 12 months , while sick leave data will be collected up to at least 24 months after r and omization . The primary outcome of the study is sick leave and will be based on register data from the National Insurance Administration . Secondary outcomes include self-reported data on disability , pain , and psychological variables . Conclusions To our knowledge , the CINS trial will be the largest , r and omized trial of psychological and nutritional interventions for chronic low back pain patients to date . It will provide important information regarding the effectiveness of CBT and seal oil for chronic low back pain patients .Trial Registration http://www . clinical trials.gov , with registration number NCT00463970 Background Return to work after gynaecological surgery takes much longer than expected , irrespective of the level of invasiveness . In order to empower patients in recovery and return to work , a multidisciplinary care program consisting of an e-health intervention and integrated care management including participatory workplace intervention was developed . Methods / Design We design ed a r and omized controlled trial to assess the effect of the multidisciplinary care program on full sustainable return to work in patients after gynaecological surgery , compared to usual clinical care . Two hundred twelve women ( 18 - 65 years old ) undergoing hysterectomy and /or laparoscopic adnexal surgery on benign indication in one of the 7 participating ( university ) hospitals in the Netherl and s are expected to take part in this study at baseline . The primary outcome measure is sick leave duration until full sustainable return to work and is measured by a monthly calendar of sickness absence during 26 weeks after surgery . Secondary outcome measures are the effect of the care program on general recovery , quality of life , pain intensity and complications , and are assessed using question naires at baseline , 2 , 6 , 12 and 26 weeks after surgery . Discussion The discrepancy between expected physical recovery and actual return to work after gynaecological surgery contributes to the relevance of this study . There is strong evidence that long periods of sick leave can result in work disability , poorer general health and increased risk of mental health problems . We expect that this multidisciplinary care program will improve peri-operative care , contribute to a faster return to work of patients after gynaecological surgery and , as a consequence , will reduce societal costs considerably . Trial registration Netherl and s Trial Register ( NTR ) : Study Design . R and omized clinical trial comparing two interventions in employees sick-listed 3 to 16 weeks because of low back pain ( LBP ) . Objective . To compare 1-year return to work ( RTW ) , pain , disability and physical and mental health dimensions in subjects offered a hospital-based multidisciplinary intervention or a brief intervention . Summary of Background Data . Previous studies in sick-listed employees with LBP have indicated efficacy of both brief and more comprehensive multidisciplinary interventions . However , it remains unknown , which is the more effective , and which elements are instrumental in furthering RTW , and improving health . Methods . The brief intervention comprised clinical examination and advice offered by a rehabilitation physician and a physiotherapist . In the multidisciplinary intervention , this intervention was supplemented with the expertise of a team and the assignment of a case manager who drew up a rehabilitation plan in collaboration with the patient and the multidisciplinary team . One-year RTW was estimated by data from a comprehensive national data base of social transfer payments . Question naires were used to obtain baseline and 1-year data on Rol and Morris disability score , LBP Rating Scale , SF36 , and fear-avoidance . Results . A total of 351 patients were included and r and omized and 344 ( 98 % ) patients participated in all the consultations according to the study protocol . RTW was achieved by 125 ( 71.0 % ) participants in the multidisciplinary and 133 ( 76.0 % ) participants in the brief intervention group . The hazard ratio was 0.84 after adjustment for sex , age , smoking , compensation cl aims , disability score , and diagnosis ( 95 % confidence interval [ CI ] : 0.65–1.08,P = 0.18 ) . Multiple linear regression analysis displayed no differences in secondary outcomes , except for the mental health score ( SF36 ) , which was a little higher in the multidisciplinary intervention group than in the brief intervention group . Conclusion . Hospital-based multidisciplinary intervention may be no better than brief intervention to increase RTW and improve health in sick-listed employees with low back pain Background Multidisciplinary intervention is recommended for rehabilitation of employees sick-listed for 4 - 12 weeks due to low back pain ( LBP ) . However , comparison of a brief and a multidisciplinary intervention in a r and omised comparative trial of sick-listed employees showed similar return to work ( RTW ) rates in the two groups . The aim of the present study was to identify subgroups , primarily defined by work-related baseline factors that would benefit more from the multidisciplinary intervention than from the brief intervention . Methods A total of 351 employees sick-listed for 3 - 16 weeks due to LBP were recruited from their general practitioners . They received a brief or a multidisciplinary intervention . Both interventions comprised clinical examination and advice by a rehabilitation doctor and a physiotherapist . The multidisciplinary intervention also comprised assignment of a case manager , who made a rehabilitation plan in collaboration with the patient and a multidisciplinary team . Using data from a national data base , we defined RTW as no sickness compensation benefit disbursement for four consecutive weeks within the first year after the intervention . At the first interview in the clinic , it was ensured that sick leave was primarily due to low back problems . Question naires were used to obtain data on health , disability , demographic and workplace-related factors . Cox hazard regression analyses were used with RTW as outcome measure and hazard rate ratios ( HRR = HRmultidisciplinary/HRbrief ) were adjusted for demographic and health-related variables . An interaction term consisting of a baseline variable*intervention group was added to the multivariable regression model to analyse whether the effects of the interventions were moderated by the baseline factor . Subsequently , a new study was performed that included 120 patients who followed the same protocol . This group was analyzed in the same way to verify the findings from the original study group . Results The multidisciplinary intervention group ensured a quicker RTW than the brief intervention group in a subgroup with low job satisfaction , notably when cl aim ants were excluded . The opposite effect was seen in the subgroup with high job satisfaction . When cl aim ants were excluded , the effect was also in favour of the multidisciplinary intervention in subgroups characterised by no influence on work planning and groups at risk of losing their job . Inversely , the effect was in favour of the brief intervention in the subgroups who were able to influence the planning of their work and who had no risk of losing their job due to current sick leave . Interaction analysis of the data in the new study displayed similar or even more pronounced differences between subgroups in relation to intervention type . Conclusions Multidisciplinary intervention seemed more effective than brief intervention in subgroups of patients with low job satisfaction , no influence on work planning and feeling at risk of losing their jobs due to their sick leave as compared with subgroups not fulfilling these criteria Background Musculoskeletal disorders impose a substantial economic burden on American society , but few studies have examined the economic benefits associated with treating such disorders . The purpose of this research is to estimate the indirect economic implication s of activity limitations associated with musculoskeletal disorders and to quantifying the potential economic gains from elective surgery to treat arthritis of the knee and hip . Methods Using regression analysis with the National Health Interview Survey ( 2004 - 2010 data , n=185,829 adults ) we quantify the relationship between severity of activity limitations ( walking , sitting , st and ing , etc . ) and employment , household income , missed work days , and receipt of supplemental security income for disability . Activity limitations are combined to create an index similar to the Functional Ability Index from the Short Form 36 Health Question naire ( SF-36 ) often used in clinical trials to measure patient functional mobility . This index is included in the regression analyses . We use data from published , prospect i ve clinical trials to establish the improvement in patient functional ability following surgery to treat arthritis of the knee and hip . Results Improved physical function is associated with higher likelihood of employment , higher household income and fewer missed work days for those who are employed , and reduced likelihood of receiving supplemental security income for disability . The magnitude of the impact and statistical significance vary by activity limitation and severity . Each percentage point increase in the index value is associated with a 2-percentage-point increase in the odds of being employed , a 3-percentage-point-day decline in work days missed and an additional $ 180 in annual household income if employed , and a 2-percentage-point decline in the odds of receiving supplemental security income for disability . All estimates are statistically significant at the 0.05 level . Conclusions Using a large , representative sample of non-institutionalized adults in the U.S. , we find that physical activity limitations are associated with worse economic outcomes across multiple economic metrics . Combined with estimates of improved functional ability following knee and hip surgery , we quantify some of the economic benefits of surgery for arthritis of the knee and hip . This information helps improve underst and ing of the societal benefits of medical treatment for musculoskeletal conditions Background Posy and u , or pos pelayanan terpadu ( integrated service post ) , is a community-based activity for health services in Indonesia . According to the Indonesian Basic Health Survey , the prevalence of children under five in Indonesia who suffered from being underweight was 19.6 % . The wasting was 12.1 % and the stunting was 37.2 % in 2013 , and these values have not changed greatly from 2007 ; much greater than the WHO targets of , less than 10 % underweight , 5 % wasting , and 20 % stunting . In Aceh were 26.6 , 16.8 , and 43.3 % , respectively . Also , the participation percentages of mothers to Posy and u was about 45 % , far below the national target of 100 % . In Aceh Province , the percentage was even lower ( 34 % in 2013 ) . This study aim ed to investigate the factors influencing participation of mothers in Posy and u. Methods This research used a cross-sectional design with sample of mothers who had children under five . They were chosen by multistage r and om sampling . Sample size was determined by the WHO formula . Face-to-face interviews were carried out using a question naire . The question naire consisted of items about socio-demographic characteristics , satisfaction with Posy and u services , attitude towards Posy and u benefits , and intention to attend Posy and u. The collected data were analyzed by using EZR ( version 1.21 ) . Fisher ’s exact test was performed to examine the associations between the socio-demographic factors , attitude , satisfaction , and intention covariates with participation . Logistic regression was used to describe the strength of the relationship between the predictor variables and participation . Results There were no significant differences in age , marital status , education level , occupation , family size , and distance to Posy and u between low participation group except for the monthly household income . Among the socio-demographic factors , only monthly household income had a significant association with the frequency of mothers ’ participation . Satisfaction , attitude , and intention were associated with participation . The logistic regression showed that monitoring the nutritional status of children under five was the main reason that mothers participated in Posy and u. Mothers who were satisfied with the Posy and u services were more likely to attend than those who were dissatisfied . Respondents with intention to participate in Posy and u every month were more likely to attend than those who did not intend to attend every month . Households with low income were more likely to participate in Posy and u than households with high income . Conclusion Household income , mothers ’ satisfaction with Posy and u services , attitude towards Posy and u benefits and intention to attend Posy and u affect the participation frequency of the mother . In addition , monitoring the nutritional status of children under five was the main reason respondents attend Posy and u. Improving the quality of Posy and u services and providing qualified re sources are needed to promote mothers ’ participation Aims : To test the long term cost-benefit and cost-effectiveness of the Sherbrooke model of management of subacute occupational back pain , combining an occupational and a clinical rehabilitation intervention . Methods : A r and omised trial design with four arms was used : st and ard care , occupational arm , clinical arm , and Sherbrooke model arm ( combined occupational and clinical interventions ) . From the Quebec WCB perspective , a cost-benefit ( amount of consequence of disease costs saved ) and cost-effectiveness analysis ( amount of dollars spent for each saved day on full benefits ) were calculated for each experimental arm of the study , compared to st and ard care . Results : At the mean follow up of 6.4 years , all experimental study arms showed a trend towards cost benefit and cost effectiveness . These results were owing to a small number of very costly cases . The largest number of days saved from benefits was in the Sherbrooke model arm . Conclusions : A fully integrated disability prevention model for occupational back pain appeared to be cost beneficial for the workers ’ compensation board and to save more days on benefits than usual care or partial interventions . A limited number of cases were responsible for most of the long term disability costs , in accordance with occupational back pain epidemiology . However , further studies with larger sample s will be necessary to confirm these results Objective To evaluate the cost effectiveness , cost utility , and cost-benefit of an integrated care programme compared with usual care for sick listed patients with chronic low back pain . Design Economic evaluation alongside a r and omised controlled trial with 12 months ’ follow-up . Setting Primary care ( 10 physiotherapy practice s , one occupational health service , one occupational therapy practice ) and secondary care ( five hospitals ) in the Netherl and s , 2005 - 9 . Participants 134 adults aged 18 - 65 sick listed because of chronic low back pain : 66 were r and omised to integrated care and 68 to usual care . Interventions Integrated care consisted of a workplace intervention based on participatory ergonomics , with involvement of a supervisor , and a grade d activity programme based on cognitive behavioural principles . Usual care was provided by general practitioners and occupational physicians according to Dutch guidelines . Main outcome measures The primary outcome was duration until sustainable return to work . The secondary outcome was quality adjusted life years ( QALYs ) , measured using EuroQol . Results Total costs in the integrated care group ( £ 13 165 , SD £ 13 600 ) were significantly lower than in the usual care group ( £ 18 475 , SD £ 13 616 ) . Cost effectiveness planes and acceptability curves showed that integrated care was cost effective compared with usual care for return to work and QALYs gained . The cost-benefit analyses showed that every £ 1 invested in integrated care would return an estimated £ 26 . The net societal benefit of integrated care compared with usual care was £ 5744 . Conclusions Implementation of an integrated care programme for patients sick listed with chronic low back pain has a large potential to significantly reduce societal costs , increase effectiveness of care , improve quality of life , and improve function on a broad scale . Integrated care therefore has large gains for patients and society as well as for employers OBJECTIVE The purpose of this study was to evaluate the effectiveness of an activating intervention design ed to reduce sick leave duration in patients with emotional distress or minor mental disorders . METHOD In a 1.5-year r and omized controlled trial , 194 patients with minor mental disorders received either an experimental intervention by social workers or general practitioners ' usual care . The intervention focused on underst and ing causes , developing and implementing problem-solving strategies and promoting early work resumption . Outcome measures were sick leave duration , mental health and physical health ( question naires included the Hospital Anxiety and Depression Scale , the Four-Dimensional Symptom Question naire and SF-36 ) , all measured at baseline at and 3 , 6 and 18 months later . Multilevel analyses were used to evaluate differences between groups . RESULTS The groups did not differ significantly on any of the outcome measures , except that the experimental group reported higher satisfaction with treatment . CONCLUSION Although the intervention has benefits , it was not successful at its primary goal ( i.e. , to reduce sick leave duration in patients with emotional distress or minor mental disorders ) . Programs aim ed at the reduction of sick leave duration may yield better results if targeted at patients with more severe emotional problems than at those with exclusively emotional distress or minor mental disorders , or if delivered by caregivers who are closer to the work environment than are social workers , such as occupational physicians OBJECTIVES The aim of this study was to evaluate the effect of the Danish return-to-work ( RTW ) program on long-term sickness absence in a r and omized controlled trial in three municipalities . METHODS The intervention group comprised 1948 participants while the control group comprised 1157 participant receiving ordinary sickness benefit management ( OSM ) . Study participants were working-age adults receiving long-term ( ≥8 weeks or more ) benefits , included regardless of reason for sickness absence or employment status . Each beneficiary was followed-up for a maximum period of 52 weeks . Cox proportional hazards model was used to estimate hazard ratios ( HR ) for return to work ( RTW ) with 95 % confidence intervals ( 95 % CI ) . RESULTS The intervention effect differed significantly between the municipalities ( P=0.00005 ) . In one municipality ( M2 ) the intervention result ed in a statistically significant increased rate of recovery from long-term sickness absence ( HR 1.51 , 95 % CI 1.31 - 1.74 ) . In the other two municipalities , the intervention did not show a statistically significant effect ( HR M11.12 , 95 % CI 0.97 - 1.29 , and HR M30.80 , 95 % CI 0.63 - 1.03 , respectively ) . Adjustment for a series of possible confounders only marginally altered the estimated HR . CONCLUSION The effect of the intervention differed substantially between the three municipalities , indicating that that context ual factors are of major importance for success or failure of this complex intervention Purpose Sickness absence and exclusion from the labour market due to mental health problems ( MHPs ) is a growing concern in many countries . Knowledge about effective return-to-work ( RTW ) intervention models is still limited , but a multidisciplinary , coordinated and tailored approach has shown promising results in the context of musculoskeletal disorders . The purpose of this study was to assess the effectiveness of this approach as implemented among sickness absence beneficiaries with MHPs . Methods In a quasi-r and omised , controlled trial , we assessed the intervention ’s effect in terms of time to RTW and labour market status after 1 year . We used two different analytical strategies to compare time to RTW between participants receiving the intervention ( n = 88 ) and those receiving conventional case management ( n = 80 ) : ( 1 ) a traditional multivariable regression analysis controlling for measured confounding , and ( 2 ) an instrumental variable ( IV ) analysis controlling for unmeasured confounding . Results The two analytical approaches provided similar results in terms of a longer time to RTW among recipients of the intervention ( HR = 0.50 ; 95 % CI 0.34–0.75 ) , although the estimate provided by the IV- analysis was non-significant ( HR = 0.70 ; 95 % CI 0.23–2.12 ) . After 1 year , more recipients of the intervention than of conventional case management were receiving sickness absence benefits ( p = 0.031 ) . Conclusion The intervention delayed RTW compared to conventional case management , after accounting for measured confounding . The delayed RTW may be due to either implementation or program failure , or both . It may also reflect the complexity of retaining employees with mental health problems in the workplace & NA ; Multidisciplinary programmes using a vocational approach can enhance work return in chronic pain patients , but little is known about the long‐term effects of rehabilitation . The current study examined the patterns of sickness absence 10 years after participation in 3 treatment groups ( physiotherapy , cognitive behavioural therapy , and vocational multidisciplinary rehabilitation ) in comparison to a control group receiving treatment‐as‐usual . Cost‐effectiveness was also assessed . Two hundred fourteen patients participated in a r and omized controlled trial and were followed‐up via register data 10 years after the interventions . On average , persons in multidisciplinary rehabilitation had 42.98 fewer days on sickness absence per year compared to those treated‐as‐usual ( 95 % confidence interval −82.45 to −3.52 , P = 0.03 ) . The corresponding reduction of sickness absence after physiotherapy and cognitive behavioural therapy was not significantly different from the control group . The effect of rehabilitation seems to be more pronounced for disability pension than for sick leave . The economic analyses showed substantial cost savings for individuals in the multidisciplinary group compared to the control group . Intensive multidisciplinary rehabilitation for persistent back and neck pain reduces sickness absence 10 years after intervention and shows greater cost reductions than physiotherapy and cognitive behavioural therapy alone BACKGROUND Major depression has far-reaching consequences for work functioning and absenteeism . In most cases depression is treated by medication and clinical management . The addition of occupational therapy ( OT ) might improve outcome . We determined the cost-effectiveness of the addition of OT to treatment as usual ( TAU ) . METHOD Sixty-two adults with major depression and a mean absenteeism of 242 days were r and omized to TAU ( out-patient psychiatric treatment ) or TAU+OT [ 6 months , including ( i ) diagnostic phase with occupational history and work reintegration plan , and ( ii ) therapeutic phase with individual sessions and group sessions ] . Main outcome domains were depression , work resumption , work stress and costs . Assessment s were at baseline and at 3 , 6 , 12 and 42 months . RESULTS The addition of OT to TAU : ( i ) did not improve depression outcome , ( ii ) result ed in a reduction in work-loss days during the first 18 months , ( iii ) did not increase work stress , and ( iv ) had a 75.5 % probability of being more cost-effective than TAU alone . CONCLUSION Addition of OT to good clinical practice does not improve depression outcome , improves productivity without increasing work stress and is superior to TAU in terms of cost-effectiveness Because of the increasing frequency of sick-leave in Sweden the General Health Insurance has directed funds for active rehabilitation by study ing the possibilities for long-time sick-leave patients to go back to work . In the present study 38 subjects were r and omized to an intervention group and a control group and followed for 3 years . In the intervention group , individual rehabilitation programs were provided and the patients were encouraged to actively deal with and improve their working situation . Also , they were influenced to accept activity and an active life style with a goal in life as an important and valuable concept . There was an obvious tendency of those in the intervention group to return to work more readily , however , the difference between the groups was not statistically significant Objectives Major depressive disorder ( MDD ) is associated with absenteeism . In this study , the effectiveness of collaborative care , with a focus on return to work ( RTW ) , was evaluated in its effect on depressive symptoms and the duration until RTW in sick-listed workers with MDD in the occupational health setting . Methods In this r and omised controlled trial , 126 sick-listed workers with MDD were r and omised to usual care ( N=61 ) or collaborative care ( N=65 ) . Collaborative care was applied by the occupational physician care manager , supported by a web-based tracking system and a consultant psychiatrist . Primary outcome measure was time to response . Secondary outcome measures were time to remission , depressive symptoms as continuous measure and the duration until full RTW . Results Collaborative care participants had a shorter time to response , with a difference of 2.8 months . However , no difference was found on time to remission or depressive symptoms as continuous measure . With a mean of 190 days in the collaborative care group , and 210 days in the usual care group , the groups did not differ significantly from each other in the duration until full RTW . Adherence to the collaborative care intervention was low . Conclusions These results do not justify a widespread implementation of collaborative care in occupational healthcare , as it was operationalised in this study . However , since the study might have been underpowered for RTW and because treatment integrity was low , further research , with larger sample sizes , is needed to develop the best fitting ( collaborative care ) model for addressing RTW in depressed sick-listed workers . Trial registration : IS RCT OBJECTIVES The purpose of this study was to assess the effects of early part-time sick leave on return to work ( RTW ) and sickness absence among patients with musculoskeletal disorders . METHODS A r and omized controlled trial was conducted in six occupational health units of medium- and large-size enterprises . Patients aged 18 - 60 years with musculoskeletal disorders ( N=63 ) unable to perform their regular work were r and omly allocated to part- or full-time sick leave . In the former group , workload was reduced by restricting work time by about a half . Remaining work tasks were modified when necessary , as specified in a " fit note " from the physician . The main outcomes were time to return to regular work activities and sickness absence during 12-month follow-up . RESULTS Time to RTW sustained for ≥4 weeks was shorter in the intervention group ( median 12 versus 20 days , P=0.10 ) . Hazard ratio of RTW adjusted for age was 1.60 [ 95 % confidence interval ( 95 % CI ) 0.98 - 2.63 ] and 1.76 ( 95 % CI 1.21 - 2.56 ) after further adjustment for pain interference with sleep and previous sickness absence at baseline . Total sickness absence during the 12-month follow-up was about 20 % lower in the intervention than the control group . Compliance with the intervention was high with no discontinuations of part-time sick leave due to musculoskeletal reasons . CONCLUSIONS Early part-time sick leave may provide a faster and more sustainable return to regular duties than full-time sick leave among patients with musculoskeletal disorders . This is the first study to show that work participation can be safely increased with early part-time sick leave Objectives To evaluate whether adjuvant occupational therapy ( OT ) can improve the effectiveness of treatment-as-usual ( TAU ) in sick-listed employees with major depression . Methods In total , 117 employees sick-listed for a median duration of 4.8 months ( IQR=2.6 to 10.1 months ) because of major depression were r and omised to TAU ( n=39 ) or adjuvant OT ( TAU+OT ; n=78 ) . OT ( 18 sessions ) focussed on a fast return to work ( RTW ) and improving work-related coping and self-efficacy . The primary outcome was work participation ( hours of absenteeism+ duration until partial/full RTW ) . Secondary outcomes were depression , at-work functioning , and health-related functioning . Intermediate outcomes were work-related , coping and self-efficacy . Blinded assessment s occurred at baseline and 6 , 12 and 18 months follow-up . Results The groups did not significantly differ in their overall work participation ( adjusted group difference=−1.9 , 95 % CI −19.9 to + 16.2 ) . However , those in TAU+OT did show greater improvement in depression symptoms ( −2.8 , −5.5 to −0.2 ) , an increased probability of long-term symptom remission ( + 18 % , + 7 % to + 30 % ) , and increased probability of long-term RTW in good health ( GH ) ( + 24 % , 12 % to 36 % ) . There were no significant group differences in the remaining secondary /intermediate outcomes . Conclusions In a highly impaired population , we could not demonstrate significant benefit of adjuvant OT for improving overall work participation . However , adjuvant OT did increase long-term depression recovery and long-term RTW in GH ( ie , full RTW while being remitted , and with better work and role functioning ) . Trial Registration Dutch Trial Register NTR2057 Objective : To determine the effectiveness and cost-effectiveness of a return-to-work outpatient multidisciplinary treatment programme for sick-listed workers with non-specific upper extremity musculoskeletal complaints . Methods : A r and omized controlled trial with a 1-year follow-up was carried out . Thirty-eight subjects were allocated to multidisciplinary treatment ( intervention , n=23 ) , or to usual care provided by occupational health services ( n=15 ) . The intervention consisted of psychological and physical sessions provided by a medical specialist , a psychologist , a physiotherapist and an occupational therapist . It aims at reconditioning , “ de-medicalizing ” , unrestrained moving and return-to-work . The intervention process was evaluated on compliance to the protocol and the effectiveness of its components . The individual outcome variable was the severity of complaints . The societal outcomes included return-to-work and costs . Measurements were performed at baseline and after 2 , 6 and 12 months . Mixed model analyses were used for analysis . Results : The intervention achieves its aims : physical disabilities ( P=0.039 ) , kinesiophobia ( P<0.001 ) and physical functioning ( P=0.016 ) improved significantly as compared to usual care . In addition , the intervention was significantly more effective in reducing the severity of complaints than usual care . The intervention was equally effective compared to usual care in terms of return-to-work ( 86 % in the intervention group vs. 73 % in the usual care group ) . The extra total costs and the extra gains in terms of return-to-work were not significantly higher for the intervention as compared to usual care after 12 months . Conclusion : Multidisciplinary treatment affects individuals positively , but shows no significant difference in ( cost- ) effectiveness on the societal level as compared to usual care Objectives Given the individual and economic burden of chronic work disability in low back pain patients , there is a need for effective preventive interventions . The aim of the present study was to investigate whether problem-solving therapy had a supplemental value when added to behavioral grade d activity , regarding days of sick leave and work status . Design R and omized controlled trial . Patients and Setting Employees who were recently on sick leave as a result of nonspecific low back pain were referred to the rehabilitation center by general practitioner , occupational physician , or rehabilitation physician . Forty-five employees had been r and omly assigned to the experimental treatment condition that included behavioral grade d activity and problem-solving therapy ( GAPS ) , and 39 employees had been r and omly assigned to behavioral grade d activity and group education ( GAGE ) . Outcome Measures Days of sick leave and work status . Data were retrieved from occupational health services . Results Data analyses showed that employees in the GAPS group had significantly fewer days of sick leave in the second half-year after the intervention . Moreover , work status was more favorable for employees in this condition , in that more employees had a 100 % return-to-work and fewer patients ended up receiving disability pensions one year after the intervention . Sensitivity analyses confirmed these results . Conclusions The addition of problem-solving therapy to behavioral grade d activity had supplemental value in employees with nonspecific low back pain This study was design ed to evaluate the effectiveness of a multidisciplinary rehabilitation programme offered to a general population with 90 days of sick-leave due to non-specific musculoskeletal pain . The results concerning return to work and re-sick-listing during a follow-up period of five years were evaluated for Swedes and immigrants separately . Compared to a control group , the rehabilitation offer result ed in improved work stability after work return among the Swedes . The immigrants , as a group , did not benefit from the programme compared to the controls in primary care & NA ; The aim of the present study was to evaluate the long‐term outcome of a behavioural medicine rehabilitation programme and the outcome of its two main components , compared to a ‘ treatment‐as‐usual ’ control group . The study employed a 4 × 5 repeated‐ measures design with four groups and five assessment periods during a 3‐year follow‐up . The group studied consisted of blue‐collar and service/care workers on sick leave , identified in a nationwide health insurance scheme in Sweden . After inclusion , the subjects were r and omised to one of the four conditions : behaviour‐oriented physiotherapy ( PT ) , cognitive behavioural therapy ( CBT ) , behavioural medicine rehabilitation consisting of PT+CBT ( BM ) and a ‘ treatment‐as‐usual ’ control group ( CG ) . Outcome variables were sick leave , early retirement and health‐related quality of life . A cost‐effectiveness analysis , comparing the programmes , was made . The results showed , consistently , the full‐time behavioural medicine programme being superior to the three other conditions . The strongest effect was found on females . Regarding sick leave , the mean difference in the per‐ protocol analysis between the BM programme and the control group was 201 days , thus reducing sick leave by about two‐thirds of a working year . Rehabilitating women has a substantial impact on costs for production losses , whereas rehabilitating men seem to be effortless with no significant effect on either health or costs . In conclusion , a full‐time behavioural medicine programme is a cost‐effective method for improving health and increasing return to work in women working in blue‐collar or service/care occupations and suffering from back/neck pain Abstract A functional restoration ( FR ) program , dealing with a combination of intensive physical and ergonomic training , psychological pain management , and patient education , was tested in two r and omized , parallel group studies . In one of these patients following the FR program were compared with a non-treated control group ( project A ) , and in the other with patients on two less intensive treatment programs ( project B ) . A total of 238 chronic low back pain patients participated in the two studies , 106 entering project A and 132 project B. Patients from the two projects were comparable except that the patients in project A were recruited from all over the country , whereas patients in project B all were living in and around Copenhagen . Thirteen patients never started any treatment , and 20 patients ( 9 % ) dropped out during the treatment period . Of the 207 who completed treatment , 89 % returned a mailed question naire 5 years later . This was the case for 55 % of the drop-outs . The questions referred to work situation , pain level , activities of daily living , days of sick leave , contact with health care professionals , physical activity , use of medication , and a subjective overall assessment . The results show that in project A the treated group reported significantly fewer contacts with the health care system and significantly fewer days of sick leave over the 5-year follow-up period compared to the control group . In all other parameters , including work ability , there was no statistically significant difference between the two groups . In project B , patients treated in the FR program did significantly better in most measured parameters , except in leg pain , use of pain medication and sport activity , where no significant differences were found between groups . The overall result shows a positive long-term effect of the FR program , but it also shows the necessity of testing a given treatment in different projects and design s , among other things due to statistical variations Objective : To evaluate the effectiveness of guideline -based care ( GBC ) of workers with mental health problems , which promotes counseling by the occupational physician ( OP ) facilitating return to work ( RTW ) . Methods : In a r and omized controlled trial with police workers on sick leave due to mental health problems ( n = 240 ) , trained OPs delivered GBC in the intervention group . Time to RTW and recurrences during 1-year follow-up , analyzed using Cox proportional hazards models , were compared with usual care ( UC ) with easy access to a psychologist . Results : GBC by OPs did not result in earlier RTW than UC . Subgroup analysis showed a small effect in favor of GBC for workers with administrative functions and /or “ minor ” stress-related symptoms . Conclusions : GBC did not differ in RTW compared with UC , but may be beneficial for the majority of workers with minor stress-related disorders The pathway of surgical innovation is complex . Inherent ethical and practical characteristics make scientific evaluation of new techniques or devices by a definitive r and omized controlled trial ( RCT ) challenging . The IDEAL Collaboration ( http://www.ideal-collaboration.net ) Framework for evaluating surgical innovation describes a five stage process - Idea , Development , Exploration , Assessment and Long-term study .(1 ) Early stage studies should be design ed to facilitate and prepare the way for a rigorous evaluation by RCT . IDEAL Recommendations in the early stages ( Idea/Development ) emphasise prospect i ve design s , transparency and full reporting in open registries , to provide reliable data early in the innovation development process . At the Exploration stage , prospect i ve observational studies need to address factors such as case-mix , learning and outcomes , building co-operatively and explicitly towards a definitive evaluation study , preferably an RCT , optimising the contribution of data from non-r and omised prospect i ve evaluations ( Assessment stage ) . The Long-term stages should be characterised by registry-based surveillance for both new procedures and devices . IDEAL proposals for high quality RCTs of surgical procedures focus on three key areas : definition of the intervention ; who delivers the intervention and preferences of surgeons and patients . IDEAL Recommendations identify modifications to study design which may help address these difficult areas . We will describe examples of good practice using these suggested methods . Everyone involved in evaluating surgical innovations is invited to join the IDEAL Collaboration community and help further evolve methodology and reporting st and ards for robust trials in surgery 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 Objectives To evaluate the effectiveness of a participatory workplace intervention compared with usual care for sick-listed employees with distress , with regard to return to work ( RTW ) within the 12-month follow-up . Methods Employees with distress and sick-listed for 2–8 weeks were r and omised to a workplace intervention ( n=73 ) or to usual care ( n=72 ) . The participatory workplace intervention is a stepwise process involving the sick-listed employee and their supervisor , aim ed at reducing obstacles for RTW by reaching consensus about an action plan for RTW . Outcome variables were lasting RTW , cumulative sickness absence and stress-related symptoms . Results Overall , an HR of 0.99 ( 95 % CI 0.70 to 1.39 ) indicated no effect of the workplace intervention on lasting RTW . However , the workplace intervention significantly reduced the time until lasting RTW for employees who at baseline intended to return to work despite symptoms with an HR of 2.05 ( 95 % CI 1.22 to 3.45 ) . Employees who intended to return to work despite symptoms returned to work after 55 days in the workplace intervention group and 120 days in the usual care group . No such effect of the intervention was found for employees without baseline intentions to return to work despite symptoms ( HR=0.78 , 95 % CI 0.47 to 1.28 ) . Conclusions No overall effect of the participatory workplace intervention on lasting RTW was found . The workplace intervention appeared effective on lasting RTW for employees who at baseline intended to return to work despite symptoms . For employees who showed no baseline intention to return to work , the intervention did not have any effect . Other approaches are needed for this subgroup . This trial has been registered at the Dutch National Trial Register IS RCT N92307123 & NA ; In general , r and omized controlled studies concerning return to work have failed to demonstrate significant treatment effects for long‐lasting musculoskeletal pain , and most treatments examined have not been economically beneficial . Individuals ( n=654 ) sick‐listed for at least 8 weeks with musculoskeletal pain , selected from the Norwegian m and atory sickness insurance system and volunteering to participate , were categorized into three groups differing in a prognosis score ( good , medium , poor ) for return to work , based on a brief , st and ardized screening of psychological and physiotherapy findings . They were then r and omly assigned to three outpatient treatments with three different levels of intensity ( ordinary treatment , light multidisciplinary , and extensive multidisciplinary treatment ) . The evaluation was based on 14 months follow‐up data on return to work collected from social security records . The patients with good prognosis for return to work do equally well with ordinary treatment as with the two more intensive treatments . The patients with medium prognosis benefit equally from the two multidisciplinary treatments . The patients with poor prognosis receiving extensive multidisciplinary treatment returned to work at a higher rate than patients with poor prognosis receiving ordinary treatment , 55 vs. 37 % ( P<0.05 ) at 14 months . Multidisciplinary treatment is effective concerning return to work , when given to patients who are most likely to benefit from that treatment . Measures of pain or quality of life are not included in this study . The cost – benefit analysis of the economic returns of the light multidisciplinary and the extensive multidisciplinary treatment programs yields a positive net present social value of the treatment . A simple , st and ardized , screening instrument including only psychological and physiotherapeutic observations may be a useful clinical tool for allocating patients with musculoskeletal pain to the right level of treatment Sickness absenteeism caused by musculoskeletal disorders ( MSDs ) is a persistent and costly occupational health challenge . In a prospect i ve controlled trial , we compared the effects on sickness absenteeism of a more proactive role for insurance case managers as well as workplace ergonomic interventions with that of traditional case management . Patients with physician-diagnosed MSDs were r and omized either to the intervention group or the reference group offered the traditional case management routines . Participants filled out a comprehensive question naire at the initiation of the study and after 6 months . In addition , administrative data were collected at 0 , 6 , and 12 months after the initiation of the project . For the entire 12-month period , the total mean number of sick days for the intervention group was 144.9 ( SEM 11.8 ) days/person as compared to 197.9 ( 14.0 ) days in the reference group ( P < 0.01 ) . Compared with the reference group , employees in the intervention group significantly more often received a complete rehabilitation investigation ( 84 % versus 27 % ) . The time for doing this was reduced by half ( 59.4 ( 5.2 ) days versus 126.8 ( 19.2 ) , P < .01 ) . The odds ratio for returning to work in the intervention group was 2.5 ( 95 % confidence interval 1.2–5.1 ) as compared with the reference group . The direct cost savings were USD 1195 per case , yielding a direct benefit-to-cost ratio of 6.8 . It is suggested that the management of MSDs should to a greater degree focus on early return to work and building on functional capacity and employee ability . Allowing the case managers a more active role as well as involving an ergonomist in workplace adaptation meetings might also be beneficial Objective : To evaluate the cost-effectiveness and cost-utility of a return to work ( RTW ) program for workers on sick-leave due to low back pain ( LBP ) , comparing a workplace intervention implemented between 2 to 8 weeks of sick-leave with usual care , and a clinical intervention after 8 weeks of sick-leave with usual care . Design : Economic evaluation alongside a r and omised controlled trial ( RCT ) . Study population : Workers sick-listed for a period of 2 to 6 weeks due to LBP . Interventions : 1 . workplace assessment , work modifications and case management ) . 2 . physiotherapy based on operant behavioural principles . 3 . usual care : provided by an occupational physician . Outcomes : The primary outcome was return to work ( RTW ) . Other outcomes were pain intensity , functional status , quality of life and general health . The economic evaluation was conducted from a societal perspective . Outcomes were assessed at baseline ( after 2–6 weeks on sick-leave ) , and 12 weeks , 26 weeks , and 52 weeks after the first day of sick-leave . Results : The workplace intervention group returned to work 30.0 days ( 95 % CI=[3.1 , 51.3 ] ) earlier on average than the usual care group at slightly higher direct costs ( ratio of 1 day : € 19 ) . Workers in the clinical intervention group that had received usual care in the first 8 weeks returned to work 21.3 days ( 95 % CI= [ −74.1 , 29.2 ] ) later on average . The group that had received the workplace intervention in the first 8 weeks and the clinical intervention after 8 weeks returned to work 50.9 days ( 95 % CI=[−89.4 , −2.7 ] ) later on average . A workplace intervention was more effective than usual care in RTW at slightly higher costs and was equally effective as usual care at equal costs on other outcomes . A clinical intervention was less effective than usual care and associated with higher costs . Conclusion : The workplace intervention results in a safe and faster RTW than usual care at reasonable costs for workers on sick-leave for two to six weeks due to LBP OBJECTIVES --The aim was to combat occurrence of chronic occupational back pain . METHODS --A multidisciplinary model to manage back pain that includes both clinical and ergonomic approaches has been developed . Early detection , early clinical and ergonomic evaluations , and early active treatment make up the cornerstone of management . Detection of cases starts after four weeks of absence from work . An ergonomic intervention is implemented at six weeks . A medical specialist is involved at eight weeks . If return to work is not possible after 12 weeks , a functional recovery therapy followed by a therapeutic return to work is implemented . A multidisciplinary team decides if return to original or modified work is possible or if vocational rehabilitation is necessary . This model has been implemented by the investigators in the Sherbrooke ( Quebec , Canada ) area , and is presently being evaluated through a r and omised trial in 31 industrial settlements ( about 20,000 workers ) . A cluster r and omisation of industries and workers will allow separate testing of ergonomic and clinical interventions . RESULTS --One year after implementation , 31 of 35 of the eligible industrial sites participated in the study and 79 of 88 of the eligible workers affected by recent back pain had agreed to participate . Ergonomic and clinical interventions have been implemented as planned . Only three workers dropped out . Hence this global clinical and ergonomic management programme has been shown to be feasible in a general population . CONCLUSION --A global management programme of back pain joining ergonomic and clinical intervention with a multidisciplinary approach has not been tested yet . Linking these two strategies in a same multidisciplinary team represents a systemic approach to this multifactorial ailment . During the first year of this trial we did not find any conflict between these two interventions from the employer 's or worker 's point of view Summary Several new studies have indicated that an active approach to patients with chronic disabling low back pain ( LBP ) seems effective . Some of these studies emphasize the importance of dealing with the patient 's total situation in comprehensive multidisciplinary programs — the bio-psycho-social model . However , these programs are expensive . The aim of this study was to evaluate the rehabilitation outcome from three different active programs in terms of : ( 1 ) return-to-work rate , ( 2 ) days of sick leave , ( 3 ) health-care contacts , ( 4 ) pain and disability scores , and ( 5 ) staying physically active . The subjects included 132 patients r and omized to the study , of whom 123 started one of the treatment programs . They had all had at least 6 months of chronic LBP . The patients were r and omized into one of three programs : group 1 — a full-time , intensive 3-week multidisciplinary program , including active physical and ergonomic training and psychological pain management , followed by 1 day weekly for the subsequent 3 weeks ; group 2 — active physical training , twice a week for 6 weeks , for a total of 24h ; group 3 — psychological pain management combined with active physical training , twice a week for 6 weeks , also for a total of 24h . The results presented here are based on data collected 4 months following treatment , which shows an 86 % response rate . The initial examination and the follow-up evaluation were performed by a blinded observer . The results show that 4 months after treatment , the intensive multidisciplinary program is superior to the less intensive programs in terms of return-to-work rate , health-care contacts , pain and disability scores , and staying physically active . In conclusion , it seems that although the multidisciplinary program is initially expensive compared to the less intensive programs , the savings in sick pay , early retirement pensions , and health care contacts make it economically worthwhile . Long-term follow-up will show whether this effect continues This study aims to explore the effect of vocational intervention in a rheumatological outpatient clinic . The study is design ed as a r and omized study with intervention in 108 patients and with 93 patients serving as controls . The study population comprises patients referred for non-inflammatory diseases of the locomotor system who are all active members of the workforce and whose vocational status is threatened by their disease . Intervention consisted of sociomedical examination , multidisciplinary assessment and individual sociomedical rehabilitation plans . The study shows that intervention was an important instrument in the process of clarifying patients ' future maintenance situation as assessed 1 year after intervention ( relative risk ( RR ) = 1.2 ( CI 1.0 - 1.5 ) ) . The effect was particularly prominent among well-educated women . A non-significant effect was established for vocational status in general ( RR = 1.1 ( CI 0.8 - 1.4 ) ) . This effect was significant and positive for well-educated patients with a short-term sick leave ( maximum 6 months ) . The verified effect of early sociomedical intervention in the secondary healthcare sector warrants the permanency of routine intervention Study Design . R and omized controlled trial . Objectives . To Investigate the long-term effectiveness , costs , and effect modifiers of a mini-intervention , provided in addition to the usual care , and the incremental effect of a worksite visit for patients with subacute disabling low back pain ( LBP ) . Summary of Background Data . A mini-intervention was earlier proved to be an effective treatment for subacute LBP . Whether the beneficial effect is sustained is not known . Furthermore , modifiers of a treatment effect are largely unknown . Methods . A total of 164 patients with subacute LBP r and omized into a mini-intervention ( A , n = 56 ) , a mini-intervention plus a worksite visit ( B , n = 51 ) , or the usual care ( C , n = 57 ) . Mini-intervention consisted of a detailed assessment of the patients ’ history , beliefs , and physical findings by a physician and a physiotherapist , followed by recommendations and advice . The usual care patients received the conventional care . Pain , disability , health-related quality of life , satisfaction with care , days on sick leave , and health care consumption and costs were measured during a 24-month follow-up . Thirteen c and i date modifiers were tested for each outcome . Results . There were no differences between the three treatment arms regarding the intensity of pain , the perceived disability , or the health-related quality of life . However , mini-intervention decreased occurrence of daily ( A vs. , C , P = 0.01 ) and bothersome ( A vs. C , P < 0.05 ) pain and increased treatment satisfaction . Costs result ing from LBP were lower in the intervention groups ( A 4670 Euros , B 5990 Euros ) than in C ( C 9510 Euros ) ( A vs. C , P = 0.04 ; and B vs. C , not significant ) . The average number of days on sick leave was 30 in A , 45 in B , and 62 in C ( A vs. C , P = 0.03 ; B vs. C , not significant ) . The perceived risk for not recovering was the strongest modifier of treatment effect . Mental and mental-physical workers in A and B were less often on sick leave than those in C. Conclusions . Mini-intervention is an effective treatment for subacute LBP . Despite lack of a significant effect on intensity of low back pain and perceived disability , mini-intervention , including proper recommendations and advice , according to the “ active approach , ” is able to reduce LBP-related costs . The perceived risk of not recovering was the strongest modifier of treatment effect . In alleviating pain , the intervention was most effective among the patients with a high perceived risk of not recovering Background : To evaluate the efficacy of a multidisciplinary stress treatment programme . Methods : General practitioners referred 198 employed patients on sick leave with symptoms of persistent work-related stress . Using a waitlisted r and omised controlled trial design , the participants were r and omly divided into the following three groups : the intervention group ( IG , 69 participants ) ; treatment-as-usual control group ( TAUCG , 71 participants ) , which received 12 consultations with a psychologist , and the waitlisted control group ( WLCG , 58 participants ) . The stress treatment intervention consisted of nine 1-hour sessions conducted over 3 months . The goals of the sessions were the following : ( 1 ) identifying relevant stressors ; ( 2 ) changing the participant 's coping strategies ; ( 3 ) adjusting the participant 's workload and tasks , and ( 4 ) improving workplace dialogue . Each participant also attended a mindfulness-based stress reduction ( MBSR ) course for 2 h a week over 8 weeks . Results : The IG and TAUCG showed significantly greater symptom level ( Symptom Check List 92 ) reductions compared to the WLCG . Regarding the return to work ( RTW ) rate , 67 % of participants in the IG returned to full-time work after treatment , which was a significantly higher rate than in the TAUCG ( 36 % ) and WLCG ( 24 % ) . Significantly more participants in the IG ( 97 % ) increased their working hours during treatment compared with the participants in the control groups , TAUCG ( 71 % ) and WLCG ( 64 % ) . Conclusions : The stress treatment programme - a combination of work place-focused psychotherapy and MBSR - significantly reduced stress symptom levels and increased RTW rates compared with the WLCG and TAUCG Purpose . The aim of this study was to determine the impact of a vocational training programme on short- and long-term results after psychosomatic rehabilitation . Method . 1,590 in patients were screened for vocational integration . A high-risk group of 266 patients was r and omly assigned to the vocational training programme plus psychosomatic treatment ; treatment- as- usual served as a control condition . An occupational training was conducted at local companies , closely integrated into psychosomatic treatment . Vocational attitudes and adjustment were studied at intake , discharge , three , 12 and 24 month follow-ups . Results . More than half of the study participants were unemployment and /or long-term work-disabled harbouring strong negative attitudes toward return to work . Forty-six percent of the intervention group declined from participation , but complied with follow-up investigation . At discharge , participants of the vocational training programme had become more optimistic regarding resuming work . One year following discharge , participants of the training programme reported less absence from work . After 24 months , vocational adjustment had improved considerably among programme participants , and declined among controls and refusers . Conclusion . An intensive vocational training programme is effective in promoting positive attitudes to work , reducing work disability and promoting return-to-work . However , a r and omized design may be not optimal ; evaluation necessitates long-term follow-up In a r and omized controlled study multimodal cognitive behavioral treatment ( MMCBT ) , including physical treatment , cognitive behavioral modification , education , and examination of the work situation for each patient , was given to patients sick-listed for musculoskeletal pain ( n = 469 ) . Patients were recruited through the National Insurance System . After a pre-test by an independent physiotherapist the patients were allocated at r and om to the intervention group ( n = 312 ) or the control group ( n = 157 ) . The MMBCT program lasted for 4 weeks . The control group returned to their general practitioners , without any feedback or advice on therapy from the project . At the one year follow-up the MMCBT group had not returned to work at a higher rate than the control group receiving ordinary treatment available through their general practitioners . However , the MMCBT group had improved their ergonomic behavior , work potential , life quality , physical , and psychological health Study Design . A cluster-r and omized controlled trial . Objective . To evaluate the effects of two strategies to increase the use of active sick leave ( ASL ) among patients with low back pain ( LBP ) on improved return to work and quality of life . Summary of Background Data . Active sick leave is an option provided by the Norwegian National Insurance Administration that enables employees to return to modified duties at the workplace with 100 % of normal wages . A proactive implementation strategy increased the use of ASL for LBP patients from 11.5 % to 17.7 % compared with a passive intervention and a control group ( P = 0.006 ) . Methods . Sixty-five municipalities were r and omly assigned to a passive intervention , a proactive intervention , or a control group . The interventions , which were design ed to improve the use of ASL , were targeted at patients on sick leave for LBP for more than 16 days ( n = 6179 ) , their general practitioners , employers , and local insurance officers . The main outcome measures were the average number of days off work , the proportion of patients returning to work within 1 year , and self-reported quality of life while on sick leave . Results . The median number of days on sick leave was similar in the proactive intervention group ( 70 days ) , the passive intervention group ( 68 days ) , and the control group ( 71 days ) ( P = 0.8 ) . The proportion of patients returning to work before 50 weeks was also similar in the proactive ( 89 % ) , passive ( 89.5 % ) , and control groups ( 89.1 % ) . Response rates for the question naires that were sent to patients were low ( 38 % ) , and no significant differences were observed across the three groups for quality of life or patient satisfaction . Conclusions . It is not likely that efforts to increase the use of ASL will result in measurable economic benefits or improved health outcomes at the population level . The benefits of ASL for individual patients with LBP are not known This study examined the effects of work-related multidisciplinary rehabilitation ( MR ) on occupational participation in patients with chronic musculoskeletal disorders . A r and omized-controlled trial was carried out . The sample included patients with chronic musculoskeletal disorders and severe restrictions of work ability ( n=222 ) . Participants in the intervention group received a work-related rehabilitation programme following a comprehensive functional capacity evaluation ( FCE MR ) . Controls completed a conventional MR . The analysis was based on 1-year follow-up data . The primary outcome was stable occupational participation ( SOP ) , defined as employment with at most 6 months of sick leave after rehabilitation . The secondary outcomes were the duration of sick leave , employment status and the Pain Disability Index . We included 102 patients in our analysis ( intervention : n=55 , control : n=47 ) . Despite r and omization there were group differences . Adjusting these differences , patients of the FCE MR had 3.5 times higher odds of SOP [ 95 % confidence interval ( CI ) : 1.2–9.8 , P=0.018 ] . However , there was neither a significant difference in the duration of sick leave between both groups ( b=−8.0 weeks , 95 % CI : −17.4 to 1.4 , P=0.095 ) nor higher odds of employment in favour of the FCE MR after 1 year ( odds ratio=2.3 , 95 % CI : 0.9–5.8 , P=0.088 ) . Participants in the FCE MR reported less pain-related disabilities ( b=−6.5 , 95 % CI : −12.6 to −0.4 , P=0.038 ) . The study had a limitation in terms of group balance . However , the findings indicate that the work-related FCE MR was more effective for SOP , but did not significantly affect employment rate and sick leave duration BACKGROUND Participatory ergonomics ( PE ) are often applied for prevention of low back pain ( LBP ) . In this pilot- study , a PE-program is applied to the disability management of workers sick listed due to LBP . METHODS The process , implementation , satisfaction , and barriers for implementation concerning the PE-program were analyzed quantitatively and qualitatively for 35 workers sick listed 2 - 6 weeks due to LBP and their ergonomists . RESULTS Two-hundred- and -seventy ergonomic solutions were proposed to the employer . They were targeted more at work design and organization of work ( 58.9 % ) than at workplace and equipment design ( 38.9 % ) . They were planned mostly on a short-term basis ( 74.8 % ) . Almost half ( 48.9 % ) of the solutions for work adjustment were completely or partially implemented within 3 months after the first day of absenteeism . Most workers were satisfied about the PE-program ( median score 7.8 on a 10-point scale ) and reported a stimulating effect on return-to-work ( 66.7 % ) . Main obstacles to implementation were technical or organizational difficulties ( 50.0 % ) and physical disabilities of the worker ( 44.8 % ) . CONCLUSIONS This study suggests that compliance , acceptance , and satisfaction related to the PE-program were good for all participants . Almost half of the proposed solutions were implemented Study Design . R and omized clinical trial of 2 interventions in 351 employees sick listed due to low back pain ( LBP ) and a subsequent validation study ( n = 120 ) to vali date results from subgroup analyses in the original study . Objective . To compose health economic analyses ( cost-effectiveness- and cost-benefit analyses ) of multidisciplinary versus brief intervention by calculating health care sector costs and sick leave benefits . Summary of Background Data . Both brief and multidisciplinary interventions have been reported to be superior relative to usual care when comparing intervention costs with saved costs for sick leave benefits . We reported similar return to work rates in a brief and a multidisciplinary intervention group , but different return to work rates in subgroups . Methods . The brief intervention comprised clinical examination and reassuring advice . The multidisciplinary intervention was conducted by a case manager and a team of specialists . The costs of medicine , health care services , and sick leave benefits were calculated on the basis of registers . Results . The mean intervention cost per patient was & OV0556;1377 higher in the multidisciplinary intervention ( n = 176 ) than in the brief intervention group ( n = 175 ) , and sick leave was not averted . However , sick leave was averted in a subgroup receiving the multidisciplinary intervention and the mean incremental intervention cost for 1 saved sick leave week in this subgroup ( n = 60 ) of patients , who thought they were at risk of losing their job or had little influence on their work situation was & OV0556;217 . The latter finding was verified in the validation study ( n = 28 ) . Conclusion . The brief intervention result ed in fewer sick leave weeks and was less expensive than the multidisciplinary intervention . The multidisciplinary intervention only outperformed the brief intervention in terms of costs in a subgroup of sick-listed employees who thought they were at risk of losing their job or had little influence on their work situation . Level of Evidence : Study design . Population -based r and omized controlled trial . Objective . To assess the effectiveness of workplace intervention and grade d activity , separately and combined , for multidisciplinary rehabilitation of low back pain ( LBP ) . Summary of Background Data . Effective components for multidisciplinary rehabilitation of LBP are not yet established . Methods . Participants sick-listed 2 to 6 weeks due to nonspecific LBP were r and omized to workplace intervention ( n = 96 ) or usual care ( n = 100 ) . Workplace intervention consisted of workplace assessment , work modifications , and case management involving all stakeholders . Participants still sick-listed at 8 weeks were r and omized for grade d activity ( n = 55 ) or usual care ( n = 57 ) . Grade d activity comprised biweekly 1-hour exercise sessions based on operant-conditioning principles . Outcomes were lasting return to work , pain intensity and functional status , assessed at baseline , and at 12 , 26 , and 52 weeks after the start of sick leave . Results . Time until return to work for workers with workplace intervention was 77 versus 104 days ( median ) for workers without this intervention ( P = 0.02 ) . Workplace intervention was effective on return to work ( hazard ratio = 1.7 ; 95 % CI , 1.2–2.3 ; P = 0.002 ) . Grade d activity had a negative effect on return to work ( hazard ratio = 0.4 ; 95 % CI , 0.3–0.6 ; P < 0.001 ) and functional status . Combined intervention had no effect . Conclusion . Workplace intervention is advised for multidisciplinary rehabilitation of subacute LBP . Grade d activity or combined intervention is not advised Compare the effects of integrated case management and usual care on patient satisfaction in employees with work-related upper extremity disorder ( WRUED ) , and consider the implication s of higher levels of satisfaction . Describe those patient-related and work-related factors that predict the severity of upper limb symptoms and the degree of functional limitation 6 and 12 months after intervention . Enumerate the factors influencing the interval before return to work in employees with WRUED who are managed by traditional or integrated case management . An integrated case management ( ICM ) approach ( ergonomic and problem-solving intervention ) to work-related upper-extremity disorders was examined in relation to patient satisfaction , future symptom severity , function , and return to work ( RTW ) . Federal workers with work-related upper-extremity disorder workers ’ compensation cl aims ( n = 205 ) were r and omly assigned to usual care or ICM intervention . Patient satisfaction was assessed after the 4-month intervention period . Question naires on clinical outcomes and ergonomic exposure were administered at baseline and at 6- and 12-months postintervention . Time from intervention to RTW was obtained from an administrative data base . ICM group assignment was significantly associated with greater patient satisfaction . Regression analyses found higher patient satisfaction levels predicted decreased symptom severity and functional limitations at 6 months and a shorter RTW . At 12 months , predictors of positive outcomes included male gender , lower distress , lower levels of reported ergonomic exposure , and receipt of ICM . Findings highlight the utility of targeting workplace ergonomic and problem solving skills Introduction In Denmark , the magnitude and impact of work disability on the individual worker and society has prompted the development of a new “ coordinated and tailored work rehabilitation ” ( CTWR ) approach . The aim of this study was to compare the effects of CTWR with conventional case management ( CCM ) on return-to-work of workers on sick leave due to musculoskeletal disorders ( MSDs ) . Methods The study was a r and omized controlled trial with economic evaluation undertaken with workers on sick leave for 4–12 weeks due to MSDs . CTWR consists of a work disability screening by an interdisciplinary team followed by the collaborative development of a RTW plan . The primary outcome variable was registered cumulative sickness absence hours during 12 months follow-up . Secondary outcomes were work status as well as pain intensity and functional disability , measured at baseline , 3 and 12 months follow-up . The economic evaluation ( intervention costs , productivity loss , and health care utilization costs ) was based on administrative data derived from national registries . Results For the time intervals 0–6 months , 6–12 months , and the entire follow-up period , the number of sickness absence hours was significantly lower in the CTWR group as compared to the control group . The total costs saved in CTWR participants compared to controls were estimated at US $ 1,366 per person at 6 months follow-up and US $ 10,666 per person at 12 months follow-up . Conclusions Workers on sick leave for 4–12 weeks due to MSD who underwent “ CTWR ” by an interdisciplinary team had fewer sickness absence hours than controls . The economic evaluation showed that — in terms of productivity loss — CTWR seems to be cost saving for the society Study Design . A r and omized controlled trial in occupational health practice was conducted . Objective . To study the efficacy of early management of workers with low back pain by occupational physicians , as compared with management by the supervisor only . Summary of Background data . Health care and university workers with back pain and on sick leave for less than 1 month were included in the study . Methods . Patients with low back pain for at least 10 days on sick leave were r and omly assigned to early management by the occupational physician ( n = 61 ) or to a reference group with management by the worker ’s supervisor during the first 3 months of sick leave ( n = 59 ) . The patients were observed for 1 year and compared in terms of time until return to work , pain intensity , functional disability , and general health perception . The occupational physicians were provided with management guidelines . Results . No significant differences were found after 3 and 12 months of follow-up evaluation in terms of time until return to work ( hazard ratio , 1.3 ; 95 % CI , 0.90–1.90 ) or in terms of other health outcomes . Recurrences , however , occurred more frequently in the intervention group , but the total duration of sick leave in 1 year did not differ between the groups . Conclusions . The findings do not show a significant positive effect of an early intervention by occupational physicians on workers with low back pain . This might reflect the early phase of disability or the low intensity of the intervention result ing from overestimation of the physicians ’ compliance with the guidelines |
13,805 | 28,602,048 | There was very low quality evidence for fewer treatment failures ( defined variously as persistent heel pain at 8 weeks , steroid injection at 12 weeks , and unrelieved pain at 6 months ) after steroid injection .
We found low quality evidence that local steroid injections compared with placebo or no treatment may slightly reduce heel pain up to one month but not subsequently . | BACKGROUND Plantar heel pain , commonly result ing from plantar fasciitis , often results in significant morbidity .
Treatment options include nonsteroidal anti-inflammatory drugs ( NSAIDs ) , orthoses , physical therapy , physical agents ( e.g. extracorporeal shock wave therapy ( ESWT ) , laser ) and invasive procedures including steroid injections .
OBJECTIVES To assess the effects ( benefits and harms ) of injected corticosteroids for treating plantar heel pain in adults . | Plantar fasciitis is one of the most common causes of foot pain in adults . In this prospect i ve study , the outcomes of local tenoxicam injection and corticosteroid therapy for the treatment of plantar fasciitis were compared . Patients were r and omly assigned to either the tenoxicam or corticosteroid group . The tenoxicam group ( n=31 ) was treated using a local injection of 1 mL of tenoxicam ( 20 mg/2 mL ) and 1 mL of 2 % lidocaine , whereas the steroid group ( n=30 ) was treated with a local 1-mL injection containing 40 mg of methylprednisolone acetate and 1 mL of 2 % lidocaine . Clinical evaluations , which were performed before the injection and 6 and 12 months after the injection , consisted of patient-assessed pain using a visual analog scale . In addition , patient satisfaction was measured using the Roles and Maudsley score . Comparison of pre- and posttreatment visual analog scale scores demonstrated a statistically significant difference in both groups ( P<.05 ) . Furthermore , no significant difference was found between the steroid and tenoxicam groups in terms of visual analog scale scores measured 12 months after injection ( P>.05 ) . The tenoxicam injection was not significantly more effective than the corticosteroid injection . However , both methods were effective and successful in treating patients with plantar fasciitis . Tenoxicam therapy appears to provide pain relief , but its effectiveness in the long term should be explored in additional studies Background The Visual Analogue Scale ( VAS ) and the Foot Health Status Question naire ( FHSQ ) are two commonly used outcome measures for evaluating foot health . This study aim ed to calculate the Minimal Important Difference ( MID ) of the VAS and the FHSQ . Methods 184 participants with plantar heel pain were recruited from the general public to take part in two r and omised trials ( 92 participants in each trial ) that studied the effectiveness of two conservative interventions for plantar heel pain . Data from these participants were used to calculate the MIDs of the VAS and the FHSQ . An anchor-based method was used to calculate the MIDs . Two distinct types of pain were investigated for the VAS : average pain and first-step pain . All four domains of the FHSQ were investigated : foot pain , foot function , footwear and general foot health . Results The MID for the VAS using the anchor-based approach was -8 mm ( 95 % CI : -12 to -4 ) for average pain and -19 mm ( 95 % CI : -25 to -13 ) for first-step pain on the 100 mm VAS . The MID for the FHSQ was 13 points ( 95 % CI : 6 to 19 ) for pain and 7 points ( 95 % CI : 1 to 13 ) for function . The MID for the footwear domain of the FHSQ was -2 points ( 95 % CI : -8 to 4 ) and 0 points ( 95 % CI : -7 to 6 ) for the general foot health domain of the FHSQ . Conclusion The results of this study provide additional evidence for MID values of the VAS and the FHSQ for plantar heel pain . This is important for clinicians and research ers as it provides a greater underst and ing of how much improvement is required by a patient before a minimal , worthwhile change is experienced . The calculated MIDs will also assist research ers with prospect i ve sample size calculations Plantar fasciitis is a common cause of heel pain . It is a disabling disease in its chronic form . It is a degenerative tissue condition of the plantar fascia rather than an inflammation . Various treatment options are available , including nonsteroidal anti-inflammatory drugs , corticosteroid injections , orthosis , and physiotherapy . This study compared the effects of local platelet-rich plasma , corticosteroid , and placebo injections in the treatment of chronic plantar fasciitis . In this double-blind study , patients were divided r and omly into 3 groups . Local injections of platelet-rich plasma , corticosteroid , or normal saline were given . Patients were assessed with the visual analog scale for pain and with the American Orthopaedic Foot and Ankle Society ( AOFAS ) Ankle and Hindfoot score before injection , at 3 weeks , and at 3-month follow-up . Mean visual analog scale score in the platelet-rich plasma and corticosteroid groups decreased from 7.44 and 7.72 preinjection to 2.52 and 3.64 at final follow-up , respectively . Mean AOFAS score in the platelet-rich plasma and corticosteroid groups improved from 51.56 and 55.72 preinjection to 88.24 and 81.32 at final follow-up , respectively . There was a significant improvement in visual analog scale score and AOFAS score in the platelet-rich plasma and corticosteroid groups at 3 weeks and at 3-month follow-up . There was no significant improvement in visual analog scale score or AOFAS score in the placebo group at any stage of the study . The authors concluded that local injection of platelet-rich plasma or corticosteroid is an effective treatment option for chronic plantar fasciitis . Platelet-rich plasma injection is as effective as or more effective than corticosteroid injection in treating chronic plantar fasciitis Objective The aim of this study was to investigate the effectiveness of device-assisted ultrasound-guided steroid injection for treating plantar fasciitis . Design An ultrasound-guided injection device design ed with space for securing a transducer and syringe was used to guide steroid injection . Patients with unilateral plantar fasciitis were enrolled and r and omly divided into device-assisted ultrasound-guided and palpation-guided groups . Pain intensity was measured using a visual analog scale and tenderness threshold . Ultrasound and pain intensity evaluations were performed before injection and at 3 wks and at 3 mos postinjection . Betamethasone ( 7 mg ) and 1 % lidocaine ( 0.5 ml ) were injected into the inflamed plantar fascia . Results Thirty-three patients who received either device-assisted ultrasound-guided or palpation-guided injection had significantly lower visual analog scale scores ( P < 0.001 ) and higher tenderness threshold ( P < 0.01 ) postinjection . However , the device-assisted group had higher tenderness threshold ( 9.02 ± 1.38 vs. 7.18 ± 2.11 kg/cm2 ; P = 0.007 ) , lower visual analog scale score ( 1.88 ± 2.13 vs. 3.63 ± 2.60 ; P = 0.046 ) , and lower hypoechogenicity incidence in the plantar fascia ( 3/16 vs. 9/16 ; P = 0.033 ) than the palpation-guided group did at 3 mos postinjection . The heel pad was significantly thin ( P = 0.004 ) in the palpation-guided group postinjection . Conclusions Device-assisted ultrasound-guided injection for treating plantar fasciitis results in better therapeutic outcomes than palpation-guided injection does Purpose The aim of this study was to assess the reliability of perifascial oedema as a sonographic criterion for selecting the most appropriate treatment ( ultrasoundguided corticosteroid injection or ultrasound-guided extracorporeal shock wave therapy ) of idiopathic plantar fasciitis ( IPF ) . Material s and methods Sixty-four patients with a clinical diagnosis of unilateral refractory IPF , treated conservatively for at least 8 weeks , were studied with highresolution ultrasound ( HRUS ) . Pain intensity was evaluated with a visual analogue scale ( VAS ) . HRUS was used to confirm IPF and identify the presence of perifascial oedema . Patients with an HRUS diagnosis of IPF were grouped according to the presence ( A ) or absence ( B ) of perifascial oedema and then r and omly allocated to treatment with corticosteroid injection ( 1 ) or extracorporeal shock wave therapy ( 2 ) . Clinical and HRUS follow-up was performed 6 weeks after treatment . Results HRUS confirmed IPF in 68,97 % of patients and identified perifascial oedema in 53.33 % . Clinical and sonographic improvements were observed in 87.5 % and 37.5 % of patients in subgroups A1 and A2 , respectively , and in 35.71 % and 92.85 % of those in subgroups B1 and B2 , respectively . Conclusions The presence of perifascial oedema may represent an effective criterion for guiding treatment decisions towards HRUS-guided corticosteroid injection . RiassuntoObiettivoValutare l’affidabilità del criterio ecografico nell’individuazione dell’edema perifasciale nella scelta della terapia mini-invasiva ( iniezione di corticosteroidi o onde d’urto , ESWT ) con guida dell’ecografia ad alta risoluzione ( HRUS ) nel trattamento della fascite plantare idiopatica ( FPI ) . Material i e metodiSessantaquattro pazienti con diagnosi clinica di FPI monolaterale , recalcitrante , trattata conservativamente per almeno 8 settimane , sono stati sottoposti ad HRUS . Il dolore è stato quantizzato con una visual analogue scale ( VAS ) . La FPI è stata verificata all’HRUS ed è stata valutata la presenza di edema perifasciale . I pazienti con diagnosi HRUS di FPI sono stati suddivisi in ( A ) presenza e ( B ) assenza di edema perifasciale e poi suddivisi r and om in trattati con ( 1 ) infiltrazione di corticosteroidi e ( 2 ) ESWT . Le rivalutazioni clinica e HRUS sono state eseguite a 6 settimane . RisultatiNel 68,97 % dei pazienti l’HRUS ha evidenziato una FPI con edema perifasciale nel 53,33 % . Nei pazienti dei sottogruppi A1 e A2 è stato evidenziato un miglioramento clinico-strumentale nel 87,5 % e nel 37,5 % dei casi , mentre nei pazienti dei sottogruppi B1 e B2 questo è stato evidenziato nel 35,71 % e nel 92,85 % dei casi . Conclusion iLa presenza dell’edema perifasciale potrebbe essere un efficace criterio nell’indirizzare la terapia verso le iniezioni di corticosteroidi con guida HRUS Objective : To investigate the effectiveness of a physiotherapy-based exercise program versus dexamethasone injection for chronic plantar fasciopathy in workers st and ing for prolonged periods of time . Design : A parallel group nonblinded r and omized controlled trial with 12-week follow-up . Setting : An outpatient sports medicine clinic in Vancouver , British Columbia , Canada . Participants : Fifty-six workers required to st and for greater than 5 h/d with chronic plantar fasciopathy took part . Diagnosis from a physiotherapist must include signs of structural changes to the plantar fascia seen on ultrasound . Interventions : The PHYSIO group included 7 physiotherapy-led exercises performed daily over a 12-week period . The INJECTION group received 1 palpation-guided dexamethasone injection followed by a daily routine of calf stretching . Main Outcome Measures : The Foot and Ankle Disability Index ( FADI ) scores 12-weeks postintervention and ultrasound-based measures of ligament appearance . Results : At follow-up , both groups reported significant improvements in FADI and visual analog scales for pain at work and with activities of daily living at 6 and 12 weeks compared with baseline scores ( P < 0.001 ) . There were no significant between-group differences . There were no significant changes to plantar fascia thickness reported at the 6- and 12-week follow-up point . Both the number of cases with focal anechoic areas and the size of these anechoic areas improved significantly in the PHYSIO ( P = 0.003 ) and INJECTION ( P < 0.001 ) groups at 12-week follow-up . Conclusions : Workers st and ing for prolonged periods experienced the same short-term therapeutic effectiveness with a physiotherapy-led exercise program compared with an injection of corticosteroid with stretching PURPOSE To compare the effectiveness of sonographically guided and palpation-guided steroid injection for the treatment of proximal plantar fasciitis . PATIENTS AND METHODS Twenty-five consecutive patients with unilateral proximal plantar fasciitis were recruited and r and omly divided into a sonographically guided group ( n = 12 ) and palpation-guided group ( n = 13 ) . Proximal plantar fascia was assessed with a 5- to 12-MHz linear-array transducer . Pain intensity was quantified using a " tenderness threshold " ( TT ) and a visual analog scale ( VAS ) . Injection of 7 mg ( 1 ml ) of betamethasone and 0.5 ml of 1 % lidocaine into the inflamed proximal plantar fascia was performed under the guidance of sonography or palpation . Patients were evaluated clinical ly and sonographically before injection and at 2 weeks , 2 months , and 1 year after injection . VAS- and TT-measured pain intensity , thickness , and echogenicity of the proximal plantar fascia , as well as the recurrence of heel pain , were assessed . RESULTS Both VAS- and TT-measured levels of pain improved significantly after steroid injection in both groups ( p < 0.001 ) . Also , the thickness decreased significantly after injection ( p < 0.01 in the palpation-guided group ; p < 0.001 in the sonographically guided group ) . The number of patients with hypoechogenicity at the proximal plantar fascia decreased after steroid injection in both groups ( p < 0.01 for both groups ) . The recurrence rate of plantar fasciitis in patients of the palpation-guided group ( 6/13 ) was significantly higher than that of the sonographically guided group ( 1/12 ) ( p < 0.05 ) . CONCLUSIONS Steroid injection can be an effective way to treat plantar fasciitis , and injection under sonographic guidance is associated with lower recurrence of heel pain 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 BACKGROUND Plantar Heel Pain Syndrome ( PHPS ) describes central ised plantar heel pain and tenderness . It can account for up to 15 % of referrals to clinicians involved in the treatment of foot pain . OBJECTIVE To compare tibial nerve block , local infiltration with steroid or both combined in the treatment of PHPS . METHODS Patients with PHPS were r and omly assigned to three treatment groups : Group 1-steroid injection to heel ; Group 2-local anaesthetic block to tibial nerve ; Group 3-both procedures . Pain visual analogue scale ( VAS ) was measured at baseline and after 1 , 6 and 26 weeks . Heel tenderness index ( HTI ) was measured at baseline and after 6 weeks . The patient rated their discomfort from the injection(s ) using a VAS . RESULTS Forty-five patients ( 27 female ) were recruited , 14 in Group 1 , 12 in Group 2 and 19 in Group 3 . Median age was 55 , disease duration was 10 months and baseline pain VAS was 7.0 cm . All groups experienced a sustained improvement in pain VAS between baseline and weeks 1 , 6 and 26 ( all p<0.0001 ) . Group 1 reported significantly lower pain VAS that those in Group 2 ( p<0.01 ) or Group 3 ( p<0.05 ) at week 6 . Group 2 found the procedure less uncomfortable than Group 1 ( p<0.01 ) . The HTI was significantly higher in Group 2 at 6 weeks compared to Group 1 ( p<0.005 ) and Group 3 ( p<0.05 ) . CONCLUSIONS This study suggests that the natural history of PHPS following an injection is encouraging , that a tibial nerve block reduces the discomfort of the procedure , that a steroid injection to the heel may accelerate improvement and that clinicians should consider a combination of both strategies Background : The present study aim ed to clinical ly examine the effects of platelet-rich plasma ( PRP ) on improvement of plantar fasciitis and its related manifestations . Patients and Methods : This single-blind r and omized controlled trial was performed on 32 consecutive patients with the final diagnosis of plantar fasciitis that were r and omly assigned to the case group ( that received PRP , n = 16 ) and the control group ( that received corticosteroid as methylprednisolone 1 ml plus lidocaine 1 ml , n = 16 ) . The endpoints in the present study were changes in the visual analog scale score and the modified Roles and Maudsley score ( RMS ) from baseline , 1-month , 3 months , and 6 months follow-up . Plantar fascia was also assessed by B-mode sonography before and also 3 months after primary assessment . Results : Regarding the pain severity , the PRP group had significantly higher mean pain score at 3 time points of before injection , as well as 1 and 3 months after PRP use when compared to the corticosteroid group ( P < 0.05 ) ; however , the control group experienced significantly higher pain severity than the PRP group at 6 months after interventions . Also , RMS was lower in PRP group than in corticosteroid group at baseline as well as at 1 and 3 months after injections ( P < 0.05 ) . In sonography assessment , no difference was revealed . Conclusion : Administration of PRP leads to significant improvement in pain severity and physical limitation in patients with plantar fasciitis . This healing effect may be begun at least 3 months after injection Background : Plantar fasciitis is a common condition routinely managed by podiatrists in the community and is widely treated conservatively . Two commonly used treatments for plantar fasciitis are customized functional foot orthoses and corticosteroid injections . While common to clinical practice , the evidence base underpinning these treatment strategies is unknown . Therefore , the aim of this systematic review was to assess the effectiveness and safety of customized functional foot orthoses and corticosteroid injections in the treatment of plantar fasciitis . Methods : A systematic literature search was conducted . Experimental studies , in English , from 1998 to 2010 were accepted for inclusion in this review . The PEDro quality assessment tool and the National Health and Medical Research Council ’s hierarchy of evidence were used to assess the quality of the included studies . Results : Six r and omized controlled trials which met the selection criteria were included in this review . Four reported on customized functional foot orthoses and 2 on corticosteroid injections . Current best available evidence highlights that both customized functional foot orthoses and corticosteroid injections can lead to a decrease in pain associated with plantar fasciitis . Additionally , customized functional foot orthoses may also provide an additional benefit in terms of increased functional ability in patients with plantar fasciitis . Corticosteroid injections may have side effects , especially pain ( from the injection ) . Conclusion : Both customized functional foot orthoses and corticosteroid injections can lead to reduction in pain associated with plantar fasciitis . While customized functional foot orthoses may increase the functional outcomes in patients with plantar fasciitis , corticosteroid injections may have side effects ( especially pain as a result of the injection ) , which may limit its acceptability BACKGROUND To determine the effectiveness of four different local injection modalities in the treatment of plantar fasciitis . METHODS In a prospect i ve r and omized multicenter study of plantar fasciitis , 100 patients were divided into four equal groups and were treated using four different methods of local injection : group A was treated with 2 mL of autologous blood alone ; group B , an anesthetic ( 2 mL of lidocaine ) combined with peppering ; group C , a corticosteroid ( 2 mL of triamcinolone ) alone ; and group D , a corticosteroid ( 2 mL of triamcinolone ) combined with peppering . The outcome was defined by using a 10-cm visual analog scale and modified criteria of the Roles and Maudsley score 3 weeks and 6 months after the injection and compared with the pretreatment condition . RESULTS The successful results in all of the groups after injections were higher than those in the pretreatment condition ( P = .000 ) . In groups C and D , in which local corticosteroid injections were used , excellent results were obtained , with superior effect in the group in which peppering was used ( P < .05 ) . CONCLUSIONS In the treatment of plantar fasciitis , combined corticosteroid injections and peppering is effective and produces better clinical results Background Calcaneal apophysitis , also commonly known as sever ’s disease , is a condition seen in children usually aged between 8–15 years . Conservative therapies , such as taping , heel lifts and orthotic intervention are accepted management practice s for calcaneal apophysitis , though there is very little high quality research examining the efficacy of such treatment modalities . Previous narrative literature review s and opinion pieces provide some evidence for the use of heel raises or orthoses . The aim of this manuscript was to complete a systemic review on the treatment options for calcaneal apophysitis as measured by pain reduction and maintenance of physical activity . Methods A search strategy completed by two review ers examined nine data bases from inception to May 2012 . Search terms included heel pain , children , adolescent , calcaneal apophysitis , sever ’s disease , treatment , and management ( full text publications , human studies ) . Systematic review s , r and omised control trials , case series , and case studies were included . The reference lists of the selected articles were also examined . The methodology , quality and risk of bias was examined and assessed using the PEDro scale . Results Nine articles were retrieved including three clinical trials involving r and omisation , two case series , two retrospective case review s , and two case reports . Effect size calculations and a meta analysis were unable to be completed due to the limited data reported within the literature . Numerous treatment options were reported throughout the literature , though few were examined against a control or alternate treatment option in well- design ed trials . The limited evidence indicated that orthoses provided greater short-term pain relief than heel raises . Health practitioners should view these results with caution , as there were apparent method ological problems with the employed study design and limited follow-up of participants . Conclusion There is limited evidence to support the use of heel raises and orthoses for children who have heel pain related to calcaneal apophysitis . Further research is needed to generate higher quality evidence with larger sample sizes , and vali date d measures of pain and function to establish effective treatment approaches for children with calcaneal apophysitis Introduction Corticosteroid injections and foot orthoses are common interventions for plantar heel pain . Previous clinical trials have found that the effectiveness of these interventions differs over time , with corticosteroid injections being more effective in the short-term ( i.e. 0–4 weeks ) and foot orthoses more effective in the longer-term ( i.e. 5–12 weeks ) . However , some of these trials have method ological weaknesses that could have caused confounding and bias , which may have led to over- or under-estimation of the effectiveness of these interventions . As a result , there is a need to compare the effectiveness of corticosteroid injections and foot orthoses in a robust clinical trial with an appropriate follow-up time . Methods This article describes the protocol for a pragmatic , parallel-group assessor-blinded r and omised trial ( Steroid injection versus foot orthoses ( SOOTHE ) heel pain trial ) . One hundred participants with plantar heel pain will be r and omly allocated ( i.e. two groups of approximately 50 ) to receive either an ultrasound-guided corticosteroid injection or prefabricated foot orthoses . Outcome measures will be obtained at baseline , 4 , 8 and 12 weeks , with two primary endpoints at 4 and 12 weeks to reflect the hypothesised temporal effects of each intervention . The primary outcome measure will be the foot pain domain of the Foot Health Status Question naire . Trial registration Australian and New Zeal and Clinical Trials Registry number ACTRN12615001266550 OBJECTIVES To compare the effectiveness of a steroid injection ( 25 mg/ml prednisolone acetate ) with a local anaesthetic control in the treatment of heel pain and to determine any advantage for patients ' comfort of using a posterior tibial nerve block to anesthetize the heel prior to infiltration . METHODS A double-blind r and omized controlled trial using a 2 x 2 design in a hospital-based rheumatology clinic . Subjects comprised 106 patients with heel pain referred by general practitioners and other rheumatologists working in Camden and Islington Health Authority . MAIN OUTCOME MEASURES heel pain reduction at 1 , 3 and 6 months , and patient comfort at the time of injection . All outcomes were measured using a 10 cm visual analogue scale . RESULTS A statistically significant reduction in pain was detected at 1 month ( P=0.02 ) in favour of steroid injection , but thereafter no differences could be detected . Patient comfort was not significantly affected by anaesthesia of the heel ( P=0.5 ) . CONCLUSIONS A steroid injection can provide relief from heel pain in the short term . There appears to be no increase in patient comfort from anaesthetizing the heel prior to infiltration Background If conservative treatment for chronic plantar fasciitis fails , often a corticosteroid injection is given . Corticosteroid injection gives temporarily pain reduction , but no healing . Blood platelets initiate the natural healing rate . GPS ® gives an eightfold concentrate platelets of patients own blood . Injection of these platelets in the attachment of the fascia to the os calcis might induce a healing rate . Methods and design A r and omized controlled multi centre trial will be performed . The study population consists of 120 patients of 18 years and older . Patients with chronic plantar fasciitis will be allocated r and omly to have a steroid injection or an autologous platelet concentrate injections . Data will be collected before the procedure , 4,8,12,26 weeks and 1 year after the procedure . The main outcome measures of this study are pain and function measured with question naires . Conclusion Recent literature show positive effects for the treatment of tendinosis with autologous platelet injections . The forthcoming trial will compare treatment for chronic plantar fasciitis with a steroid injection versus an autologous platelet injection . Our results will be published as soon as they become available . Trial Registration Trial registration number : http://www . clinical trials.gov NCT00758641 Plantar fasciitis is the most common cause of heel pain in adults . A novel alternative medical instrument , the miniscalpel-needle ( MSN ) , which is based on an acupuncture needle , has been recently developed in China . The objective of this study was to evaluate the effectiveness of the MSN release treatment versus that of traditional steroid injection for plantar fasciitis . Patients with plantar fasciitis were r and omly assigned to 2 groups and followed up for 12 months , with 29 receiving MSN treatment and 25 receiving steroid injection treatment . The results showed that visual analog scale scores for morning pain , active pain , and overall heel pain all were decreased significantly in the MSN group from 1 to 12 months after treatment . In contrast , treatment with steroid injection showed a significant effect only at the 1-month follow-up but not at 6 or 12 months after treatment . Moreover , the MSN group achieved more rapid and sustained improvements than the steroid group throughout the duration of this study . No severe side effects were observed with MSN treatment . Our data suggest that the MSN release treatment is safe and has a significant benefit for plantar fasciitis compared to steroid injection Background Plantar fasciitis is the most commonly reported cause of chronic pain beneath the heel . Management of this condition commonly involves the use of corticosteroid injection in cases where less invasive treatments have failed . However , despite widespread use , only two r and omised trials have tested the effect of this treatment in comparison to placebo . These trials currently offer the best available evidence by which to guide clinical practice , though both were limited by method ological issues such as insufficient statistical power . Therefore , the aim of this r and omised trial is to compare the effect of ultrasound-guided corticosteroid injection versus placebo for treatment of plantar fasciitis . Methods The trial will be conducted at the La Trobe University Podiatry Clinic and will recruit 80 community-dwelling participants . Diagnostic ultrasound will be used to diagnose plantar fasciitis and participants will be required to meet a range of selection criteria . Participants will be r and omly allocated to one of two treatment arms : ( i ) ultrasound-guided injection of the plantar fascia with 1 mL of 4 mg/mL dexamethasone sodium phosphate ( experimental group ) , or ( ii ) ultrasound-guided injection of the plantar fascia with 1 mL normal saline ( control group ) . Blinding will be applied to participants and the investigator performing procedures , measuring outcomes and analysing data . Primary outcomes will be pain measured by the Foot Health Status Question naire and plantar fascia thickness measured by ultrasound at 4 , 8 and 12 weeks . All data analyses will be conducted on an intention-to-treat basis . Conclusion This will be a r and omised trial investigating the effect of dexamethasone injection on pre-specified treatment outcomes in people with plantar fasciitis . Within the parameters of this protocol , the trial findings will be used to make evidence -based recommendations regarding the use of corticosteroid injection for treatment of this condition . Trial Registration Australian New Zeal and Clinical Trials Registry . ACTRN12610000239066 OBJECTIVE To investigate the efficacy of ultrasound-guided steroid injection for the treatment of proximal plantar fasciitis and to evaluate mechanical properties of the heel pad after steroid injection . DESIGN Proximal plantar fascia and heel pad were assessed with a 10-MHz linear array ultrasound transducer . Pain intensity was quantified with a tenderness threshold ( TT ) and visual analog scale ( VAS ) . The transducer was incorporated into a specially design ed device to measure mechanical properties of the heel pad . Evaluations were performed before injection and at 2 weeks and 3 months after injection . SETTING An outpatient clinic of a tertiary care center . PATIENTS Fourteen consecutive patients with unilateral proximal plantar fasciitis . INTERVENTION Ultrasound-guided injection of 7 mg betamethasone and 0.5 mL of 1 % lidocaine into the inflamed proximal plantar fascia . MAIN OUTCOME MEASURES VAS , TT , heel pad and plantar fascia thickness , and echogenicity of the proximal plantar fascia on sonogram were assessed . Mechanical properties included unloaded heel pad thickness , compressibility index , and energy dissipation ratio . RESULTS Both VAS score + /- st and ard deviation ( SD ; 5.43 + /- 2.03 , 1.39 + /- 2.19 , 0.57 + /- 1.40 at the 3 measurements , respectively ) and TT + /- SD ( 5.05 + /- 1.42 , 9.34 + /- 1.84 , 9.93 + /- 1.98 kg/cm2 at the 3 measurements , respectively ) improved significantly ( p < .001 ) after steroid injection . The mean thickness of the plantar fascia was greater in the symptomatic side than in the asymptomatic side before treatment ( 0.58 + /- 0.13 cm vs 0.40 + /- 0.11 cm , p < .001 ) . The thickness had decreased significantly 3 months after injection ( 0.46 + /- 0.12 cm at 2 weeks , 0.42 + /- 0.10 cm at 3 months , p < .001 ) . The hypoechogenicity at the proximal plantar fascia disappeared after steroid injection ( p < .001 ) . Mechanical properties of the heel pad did not change 3 months after steroid injection ( p > .05 ) . CONCLUSION Ultrasound offers an objective measurement of the therapeutic effect on proximal plantar fasciitis . Accurate steroid injection under ultrasound guidance can effectively treat proximal plantar fasciitis without significant deterioration of the mechanical properties of the heel pads The outcome of corticosteroid injection ( CSI ) and extracorporeal shock wave therapy ( ESWT ) as primary treatment of acute plantar fasciitis has been debated . The purpose of the present study was to evaluate and compare the therapeutic effects of CSI and ESWT in patients with acute ( < 6-week duration ) symptomatic plantar fasciitis . Of the 116 eligible patients , 68 were r and omized to 2 equal groups of 34 patients , each undergoing either ESWT or CSI . The ESWT method included 2000 impulses with energy of 0.15 mJ/mm(2 ) and a total energy flux density of 900 mJ/mm(2 ) for 3 consecutive sessions at 1-week intervals . In the CSI group , 40 mg of methyl prednisolone acetate plus 1 mL of lidocaine 2 % was injected into the maximal tenderness point at the inframedial calcaneal tuberosity . The success and recurrence rates and pain intensity measured using the visual analog scale , were recorded and compared at the 3-month follow-up visit . The pain intensity had reduced significantly in all patients undergoing either technique . However , the value and trend of pain reduction in the CSI group was significantly greater than those in the ESWT group ( p < .0001 ) . In the ESWT and CSI groups , 19 ( 55.9 % ) and 5 ( 14.7 % ) patients experienced treatment failure , respectively . Age , gender , body mass index , and recurrence rate were similar between the 2 groups ( p > .05 ) . Both ESWT and CSI can be used as the primary and /or initial treatment option for treating patients with acute plantar fasciitis ; however , the CSI technique had better therapeutic outcomes Plantar fasciitis is one of the most common causes of heel pain . Despite extensive efforts foot surgeons continue to debate the best modality of treatment . Analgesics , shoe inserts , stretching exercises , steroid injection , night splints , and extracorporeal shock wave therapy have proved effective in one group but fail in others . This study evaluated the efficacy of EZStep , a new foot brace for the management of plantar fasciitis . A total of 198 patients were r and omized in 2 groups ; group 1 ( study group ) received nonsteroidal anti-inflammatory drugs ( NSAIDs ; 4 - 6 weeks ) and EZStep whereas group 2 ( control group ) received either NSAID and physiotherapy alone ( 2A ) or NSAID , physiotherapy , and local steroid injection ( 2B ) . None of the patients received over-the-counter insoles or strapping of plantar arch to avoid any bias in r and omization . Evaluations included measurement of weight and height , visual analog scale ( VAS ) for pain , and Short-Form McGill Pain Question naire ( SFMPQ ) . After 8 weeks , patients were reevaluated , and assessment for the VAS and SFMPQ with treatment outcome was performed . Patients with VAS scores ≤3 were considered as excellent , ≥4 as good , and ≥7 as poor . The posttreatment evaluation showed that VAS scores were in the range from 2.97 ± 1.06 to 7.64 ± 2.9 ( 2A ) , P = .001 , 95 % confidence interval ( CI ) < −4.104 ; for 2B P = .001 , CI < −2.44 , and SFMPQ was 21.7 ± 4.5 and 69.2 ± 5.8 ( group 2A ; P = .001 , 95 % CI < −46.44 ) . Compared with group 2B the SFMPQ was 66.5 ± 4.3 ( P = .001 , 95 % CI < −30.720 ) . In group 1 as per VAS , 86 ( 73.5 % ) were evaluated as excellent , 15 ( 12.8 % ) as good , and 16 ( 13.6 % ) as poor . Our study shows that the regular use of EZStep with short course of NSAIDs ( 4 - 6 weeks ) was effective in ameliorating symptoms in more than 85 % of patients suffering from plantar fasciitis OBJECTIVE To assess the impact of ultrasonography ( US ) on local corticosteroid ( CS ) injections of painful ankle , hindfoot , and midfoot in chronic inflammatory diseases . METHODS Consecutive patients with chronic rheumatic diseases admitted to the hospital for local CS injections of painful ankle , hindfoot , or midfoot were enrolled in this study . Clinical and radiographic evaluation was performed by the physician in charge of CS injections , and US examination was performed by an independent examiner blinded to the clinical and radiologic findings . According to a r and omized weekly-periods design , the physician planned CS injections either aware ( G1 group ) or unaware ( G2 group ) of US results . In the latter case , he was nonetheless informed of US results after he had performed the injections . Impact of this information on the treatment planning was assessed in all cases . Prognostic impact of US was also evaluated by comparing the change in global assessment of efficacy of CS injections , in activity of the disease , and in the Western Ontario and McMaster Universities ( WOMAC ) subscales after 1 and 3 months , between G1 and G2 groups . RESULTS The knowledge of US findings led the physician to change his decision of local CS injections in 56 ( 82 % ) of 68 patients studied . Among 1,131 assessed sites , by clinical , radiographic , and US evaluation , injection was cancelled in 37 ( 15 % ) of 242 proposed sites , whereas it was decided in 74 ( 8 % ) additional sites . After 1 month , there was an improvement in G1 as compared with G2 groups . The mean + /- SD change in WOMAC physical function subscale was 15.6 + /- 17.5 in G1 versus 8 + /- 13 in G2 ( P = 0.0305 ) . After 3 months , only the global assessment of efficacy of CS injections was statistically greater in G1 than in G2 group ( P = 0.0170 ) . CONCLUSION US frequently led the physician to change his diagnosis of inflammatory lesions in painful foot , and consequently his planning of CS injections . Moreover , US could improve the response to local treatment Background : This study compared the effectiveness of joint mobilization combined with stretching exercises ( JM&Str ) vs steroid injection ( SI ) in the treatment of plantar fasciitis ( PF ) . Methods : A total of 43 patients ( mean age , 45.5 ± 8.5 years ; range , 30 - 60 years ; 23 females ) with PF were r and omly assigned to receive either JM&Str ( n = 22 ) or SIs ( n = 21 ) . JM&Str was applied 3 times per week for 3 weeks for a total of 9 visits . The SI group received 1 injection at baseline . The patients ’ functional scores were assessed using the Foot and Ankle Ability Measure ( FAAM ) , and pain was evaluated using the Visual Analog Scale ( VAS ) . Outcomes of interest were captured at baseline and at 3-week , 6-week , 12-week , and 1-year follow-ups . The primary aim was examined using a mixed-model analysis of variance ( ANOVA ) . Pairwise comparisons were performed to examine differences between the baseline and follow-up periods using Bonferroni e quality at an alpha level of 0.05 . Results : Age , sex , body mass index , and dorsiflexion range of motion did not significantly impact pain relief or functional outcome ( P > .05 ) at the 3- , 6- or 12-week follow-ups compared to baseline . Planned pairwise comparisons demonstrated significant improvements in pain relief and functional outcomes in both groups ( P < .05 ) at the 3- , 6- , and 12-week follow-ups compared to baseline . However , at the 12-week and 1-year follow-ups , pain and functional outcomes were significantly improved in only the JM&Str group ( P = .002 ) . The overall group-by-time interaction was statistically significant for both FAAM ( P = .001 ; F = 7.0 ) and VAS ( P = .001 ; F = 8.3 ) scores . Between-group differences favored the SI group at the 3-week ( P = .001 , P = .001 ) , 6-week ( P = .002 , P = .001 ) , and 12-week ( P = .008 , P = .001 ) follow-ups for pain relief and functional outcomes . However , no significant differences ( P = .62 , P = .57 ) were detected in the measured outcomes at the 1-year follow-up . Conclusion : Our study demonstrated that while both groups achieved significant improvements at the 3- , 6- , and 12-week follow-ups , the SI group exhibited better outcomes at all 3 time points . The noted improvements continued in only the JM&Str group for a period of time ranging from 12 weeks to 1 year . Level of Evidence : Level II , comparative study In a prospect i ve r and omized study of plantar heel pain , 44 patients were treated with injection of 1 mL of 2 % prilocaine using the peppering technique , 1 mL of 2 % prilocaine combined with 2 mL of autologous blood , or 1 mL of 2 % prilocaine mixed with 40 mg of methylprednisolone acetate . At 6-month follow-up , clinical improvement was evaluated by using a 10-cm visual analog scale and the rearfoot score of the American Orthopaedic Foot and Ankle Society . Results were analyzed using sample t-tests within groups and repeated- measures analyses of variance between groups . Mean + /- SD visual analog scale scores in the peppering technique , autologous blood injection , and corticosteroid injection groups improved from 6.4 + /- 1.1 , 7.6 + /- 1.3 , and 7.28 + /- 1.2 to 2.0 + /- 2.2 ( P < .001 ) , 2.4 + /- 1.8 ( P < .001 ) , and 2.57 + /- 2.9 ( P < .001 ) , respectively . Mean + /- SD rearfoot scores in the same groups improved from 64.1 + /- 15.1 , 71.6 + /- 1 , and 65.7 + /- 12.7 to 78.2 + /- 12.4 ( P = .018 ) , 80.9 + /- 13.9 ( P = .025 ) , and 80.07 + /- 17.5 ( P = .030 ) , respectively . There were no statistically significant differences among the groups . Good outcomes have been documented using the peppering technique and autologous blood injection for the treatment of lateral epicondylitis . Although the curative mechanisms of both injection modalities are based on a hypothesis , they seem to be good alternatives to corticosteroid injection for the treatment of plantar heel pain OBJECTIVES 1 . To determine the sex distribution of Plantar fasciitis in Harare . 2 . To determine the presence or absence of a calcaneal spur and its role in causation and hence treatment . 3 . To determine unilateral or bilateral involvement . 4 . To determine the response to steroidal injection . 5 . To determine the role of occupation and /or activities if any . DESIGN Patients presenting with heel pad pain were carefully examined , the age , sex and occupation recorded . They were followed up at two weekly intervals following treatment . SETTING This prospect i ve study was carried out at a private surgery in a low density suburb . Most patients were referred by their general practitioners and some by patients who had been treated successfully . A few were referred from towns in and around Mashonal and Central Province . SUBJECTS All patients had to satisfy the diagnosis of Plantar fasciitis . Those presenting with well known causes of pain in and around the heel were excluded . INTERVENTIONS All patients had radiographs of both heels requested . The painful heels were injected in the office with 80 mg of depo-medrol plus three to four mls of plain lignocaine using the lateral approach . RESULTS The majority of patients ( 90 % ) were female , the mean age 48.5 years . Most patients ( 60 % ) had no calcaneal spur , 64 % had unilateral disease and this was predominantly left-sided . 94 % had relief of their symptoms following a single injection . CONCLUSIONS In this study there were more females treated for Plantar fasciitis , the majority responded to a single injection . The role of occupation and /or activities require further study Plantar fasciitis is the most common cause of heel pain . Local injection modalities are among treatment options in patients with resistant pain . The aim of the present study was to evaluate the effect of local autologous whole blood compared with corticosteroid local injection in treatment of plantar fasciitis . In this r and omized controlled multicenter study , 36 patients with chronic plantar fasciitis were recruited . Patients were allocated r and omly into three treatment groups : local autologous blood , local corticosteroid injection , and control groups receiving no injection . Patients were assessed with visual analog scale ( VAS ) , pressure pain threshold ( PPT ) , and plantar fasciitis pain/disability scale ( PFPS ) before treatment , as well as 4 and 12 weeks post therapy . Variables of pain and function improved significantly in both corticosteroid and autologous blood groups compared to control group . At 4 weeks following treatment , patients in corticosteroid group had significantly lower levels of pain than patients in autologous blood and control groups ( higher PPT level , lower PFPS , and VAS ) . After 12 weeks of treatment , both corticosteroid and autologous blood groups had lower average levels of pain than control group . The corticosteroid group showed an early sharp and then more gradual improvement in pain scores , but autologous blood group had a steady gradual drop in pain . Autologous whole blood and corticosteroid local injection can both be considered as effective methods in the treatment of chronic plantar fasciitis . These treatments decrease pain and significantly improve function compared to no treatment OBJECTIVE To assess the clinimetric value of the Dutch version of the Foot Function Index ( FFI ) in comparison with the original FFI using verbal rating scales ( FFI-5pt ) rather than visual analog scales ( VAS ) . METHODS A prospect i ve study was performed on 206 patients with nontraumatic forefoot complaints . Scoring , internal consistency , and construct validity of the FFI-5pt were compared with those of the original FFI , which rates all items on VAS . We also studied agreement between the scores at baseline and after one and 8 weeks and the scale scores with regard to sex , age , presence of osteoarthritis , limitation of mobility , bodily pain , and poor physical functioning ( using SF-36 ) . RESULTS Some items were not applicable ; removal of these items left 2 scales ( Pain and Disability ) with high internal consistency ( alpha = 0.88 to 0.94 ) and good agreement between both versions ( intraclass correlation coefficient 0.64 to 0.79 ) . Principal component analysis with varimax rotation using a forced 2 factor model fitted well ( 65 % explained variance ) . Test-retest reliability was high ( ICC 0.70 to 0.83 ) , while the stability over 8 weeks was lower , but still good ( ICC 0.63 to 0.71 ) . Responsiveness to change was low to moderate . However , a small number of patients reported an overall change ( 19 % ) . Scores of patients with limited mobility and poor physical health ( SF-36 ) were higher than those of patients with fewer physical problems , indicating good concurrent validity . CONCLUSION The FFI-5pt is a suitable generic measure . Its clinimetric properties are comparable with those of the original FFI . Its administration and data entry are less time consuming . However , responsiveness has to be more exactly assessed in an intervention study Objective : To describe and compare two extracorporeal shock wave therapy techniques for the treatment of painful subcalcaneal spur . Design : R and om assignment to two groups of treatment with two and eight months follow-up . Setting : The data were collected in out patients . Subjects : Forty-five subjects with a history of at least six months of heel pain were studied . Interventions : Each subject received a three-session ultrasound-guided extracorporeal shock wave therapy ( performed weekly ) . Perpendicular technique was used in group A ( n=22 , mean age 59.3 ± 12 years ) and tangential technique was used in group B ( n= 23 , mean age 58.8 ± 12.3 years ) . Main outcome measures : Mayo Clinical Scoring System was used to evaluate each subject before the treatment and at two and eight months follow-up . Results : Mayo Clinical Scoring System pretreatment scores were homogeneous between the groups ( group A 55.2 ±18.7 ; group B 53.5 ± 20 ; P>0.05 ) . In both groups there was a significant ( P<0.05 ) increase in the Mayo Clinical Scoring System score at two months ( group A 83.9 ± 13.7 ; group B 80 ± 15,8 ) and eight months ( group A 90 ± 10.5 ; group B 90.2 ±8.7 ) follow-up . No significant differences were obtained comparing the Mayo Clinical Scoring System scores of the two groups at two and eight months follow-up . Conclusions : There was no difference between the two techniques of using extracorporeal shock wave therapy . The tangential technique was found to be better tolerated as regards treatment-induced pain , allowing higher energy dosages to be used OBJECTIVE To compare ultrasonography with bone scintigraphy in the diagnosis of plantar fasciitis and to compare ultrasound-guided injection with palpation-guided injection in the management of idiopathic plantar fasciitis . METHODS Twenty-three patients with a clinical diagnosis of idiopathic plantar fasciitis in 28 heels underwent ultrasonography and bone scintigraphy of both heels at baseline . The patients were r and omized to ultrasound- or palpation-guided injection of triamcinolone hexacetonide and xylocaine into the plantar fascia . The 100 mm visual analogue scale ( VAS ) of pain , the heel tenderness index ( HTI ) , and ultrasonography were performed at baseline and follow-up ( mean=13.4 weeks ) . RESULTS The mean thickness ( + /-st and ard error of the mean ) of the plantar fascia , measured by ultrasonography , was 5.7+/-0.3 mm in symptomatic heels as compared with 3.8+/-0.2 mm in asymptomatic heels ( P<0.001 ) . Ultrasonography findings correlated with bone scintigraphic findings in the diagnosis of plantar fasciitis ( P<0.001 ) . Fourteen heels were r and omized to ultrasound-guided injection , 10 heels were r and omized to palpation-guided injection and four heels were not injected . Ultrasound- and palpation-guided injection result ed in significant mean improvements in VAS [ 39.6+/-9.2 ( ultrasound ) vs 41.5+/-8 ( palpation ) ] and HTI [ 1.35+/-0.2 ( ultrasound ) vs 1.3+/-0.4 ( palpation ) ] . There was no significant difference in the response rate following corticosteroid injection by either modality ( ultrasound=13/14 , palpation=8/10 ) . Following injection , the mean thickness of the plantar fascia decreased from 5.7+/-0.3 mm to 4.65+/-0.4 mm ( P<0.01 ) . CONCLUSION Ultrasonography and bone scintigraphy are equally effective in the diagnosis of plantar fasciitis . Ultrasound-guided injection is effective in the management of plantar fasciitis but is not more effective than palpation-guided injection . Ultrasonography may be used as an objective measure of response to treatment in plantar fasciitis Background : Treatment options for plantar fasciitis have result ed in varied patient outcomes . The aim of this study was to compare a novel treatment , cryopreserved human amniotic membrane ( c-hAM ) , to a traditional treatment , corticosteroid . Our hypothesis was that c-hAM would be safe and comparable to corticosteroids for plantar fasciitis in regard to patient outcomes . Methods : A r and omized , controlled , double-blind , single-center pilot study was completed . Patients were r and omized into one of 2 treatment groups : c-hAM or corticosteroid . Patients received an injection at their initial baseline visit with an option for a second injection at their first 6-week follow-up . Total follow-up was obtained for 12 weeks after the most recent injection . The primary outcome measurement was the Foot Health Status Question naire ( FHSQ ) . The secondary outcome measurements were the Visual Analog Scale ( VAS ) and verbally reported percentage improvement . Data were analyzed between groups for the 2 different cohorts ( 1 injection versus 2 injections ) . Twenty-three patients had complete follow-up . Fourteen were r and omized to receive corticosteroid and 9 were r and omized to receive c-hAM . Results : Three patients in each group received second injections . With the numbers available , the majority of outcome measurements showed no statistical difference between groups . The corticosteroid did , however , have greater FHSQ shoe fit improvement ( P = .0244 ) at 6 weeks , FHSQ general health improvement ( P = .0132 ) at 6 weeks , and verbally reported improvement ( P = .041 ) at 12 weeks in the one-injection cohort . Cryopreserved hAM had greater FHSQ foot pain improvement ( P = .0113 ) at 18 weeks in the 2-injection cohort . Conclusion : Cryopreserved hAM injection may be safe and comparable to corticosteroid injection for treatment of plantar fasciitis . This is a pilot study and requires further investigation . Level of Evidence : Level I , prospect i ve r and omized trial Background Extracorporeal shockwave treatment has shown mixed short-term results for plantar fasciitis . However , the long-term results are not available . Hypothesis Long-term results of shockwave treatment are comparable with short-term results . Study Design R and omized controlled clinical trial ; Level of evidence , 1 . Methods This prospect i ve study consisted of 149 patients ( 168 heels ) with an established diagnosis of chronic plantar fasciitis , including 79 patients ( 85 heels ) in the shockwave treatment group and 70 patients ( 83 heels ) in the control group . In the shockwave group , patients received 1500 impulses of shockwaves at 16 kV to the affected heel in a single session . Patients in the control group received conservative treatment consisting of nonsteroidal anti-inflammatory drugs , orthotics , physical therapy , an exercise program , and /or a local cortisone injection . Patients were evaluated at 60 to 72 months ( shockwave group ) or 34 to 64 months ( control group ) with a 100-point scoring system including 70 points for pain and 30 points for function . The clinical outcomes were rated as excellent , good , fair , or poor . Results Before treatment , the groups showed no significant differences in the scores for pain and function . After treatment , the shockwave group showed significantly better pain and function scores as compared with the control group . The overall results were 69.1 % excellent , 13.6 % good , 6.2 % fair , and 11.1 % poor for the shockwave group ; and 0 % excellent , 55 % good , 36 % fair , and 9 % poor for the control group ( P < .001 ) . The recurrence rate was 11 % ( 9/81 heels ) for the shockwave group versus 55 % ( 43/78 heels ) for the control group ( P < .001 ) . There were no systemic or local complications or device-related problems . Conclusion Extracorporeal shockwave treatment is effective and safe for patients with plantar fasciitis , with good long-term results In the past decade , health-related quality -of-life ( HRQoL ) assessment has become an important tool to measure change as a result of treatment in clinical trials . The aim of this project was to compare and contrast two foot-specific HRQoL question naires : the Foot Function Index ( FFI ) and the Foot Health Status Question naire ( FHSQ ) . To assist in this process , a quasi-experimental trial was performed to evaluate the effectiveness of foot orthoses in improving HRQoL in people suffering from plantar fasciitis . The results from this study found that the FFI is generally less responsive to change , particularly in the domain of Activity Limitation . Nevertheless , significant improvements were found for two out of the three domains ( Pain and Disability , but not Activity Limitation ) for the FFI , as well as the overall score of FFI . In contrast , all four domains ( Pain , Function , Footwear and General Foot Health ) of the FHSQ showed significant improvement . Our experience with the question naires also revealed that certain questions in the Activity Limitation domain of the FFI can lead to inconsistent scoring , thus casting doubts over the suitability of this domain for use with patients with plantar fasciitis . Therefore , the FHSQ has several advantages when evaluating HRQoL in patients being treated with foot orthoses for plantar fasciitis , and should be viewed as the preferred question naire Background Plantar fasciitis is a common cause of heel pain . The aim of this study was twofold : to compare steroid injection with placebo injection and to compare ultrasound guided with unguided steroid injection in the management of this condition . Methods 65 patients with inferior heel pain were recruited between November 2008 and June 2011 . Heel pain was measured using a visual analogue scale ( VAS ) at baseline and follow-up 6 and 12 weeks after injection . Results 22 patients were r and omised to ultrasound guided steroid injection , 21 patients to palpation guided steroid injection and 22 to ultrasound guided placebo injection . There was a significant difference in VAS scores between the groups at 6 and 12 weeks ( p=0.018 and p=0.004 , respectively ) . There was a 19.7 ( 95 % CI 2.5 to 37.0 ) difference in mean VAS scores at 6 weeks between the ultrasound guided steroid group and the placebo group and a 24.0 ( 95 % CI 6.6 to 41.3 ) difference between the unguided steroid group and the placebo group at 6 weeks . At 12 weeks , the mean difference was 25.1 ( 95 % CI 6.5 to 43.6 ) and 28.4 ( 95 % CI 11.1 to 45.7 ) respectively between both steroid injection groups and the placebo group . There was no difference in VAS scores following steroid injection between the ultrasound guided and the unguided groups at either time point . Plantar fascia thickness was significantly reduced after injection in both active treatment groups ( p=0.00 ) . Conclusions In this study , steroid injection showed a clear benefit over placebo at 6 weeks and this difference was maintained at 12 weeks . Trial Registration No IS RCT N79628180 ( www.controlled-trials.com ) PURPOSE The purpose of this study was to conduct a r and omized trial of radiation therapy for plantar fasciitis and to compare radiation therapy with local steroid injections . METHODS AND MATERIAL S Between March 2013 and April 2014 , 128 patients with plantar fasciitis were r and omized to receive radiation therapy ( total dose of 6.0 Gy applied in 6 fractions of 1.0 Gy three times a week ) or local corticosteroid injections a 1 ml injection of 40 mg methylprednisolone and 0.5 ml 1 % lidocaine under the guidance of palpation . The results were measured using a visual analog scale , a modified von Pannewitz scale , and a 5-level function score . The fundamental phase of the study was 3 months , with a follow-up period of up to 6 months . RESULTS The median follow-up period for all patients was 12.5 months ( range , 6.5 - 18.6 months ) . For the radiation therapy patients , the median follow-up period was 13 months ( range , 6.5 - 18.5 months ) , whereas in the palpation-guided ( PG ) steroid injection arm , it was 12.1 months ( range , 6.5 - 18.6 months ) . After 3 months , results in the radiation therapy arm were significantly superior to those in the PG steroid injection arm ( visual analog scale , P<.001 ; modified von Pannewitz scale , P<.001 ; 5-level function score , P<.001 ) . Requirements for a second treatment did not significantly differ between the 2 groups , but the time interval for the second treatment was significantly shorter in the PG steroid injection group ( P=.045 ) . CONCLUSION This study confirms the superior analgesic effect of radiation therapy compared to mean PG steroid injection on plantar fasciitis for at least 6 months after treatment BACKGROUND Many treatment options for plantar fasciitis currently exist , some with great success in pain relief . The objective of our study was to compare the use of intralesional steroids with platelet-rich plasma ( PRP ) , using pain scales and functional evaluation , in patients with plantar fasciitis who did not respond to conservative treatment . METHODS A controlled , r and omized , blinded clinical assay was performed . Patients were assigned to one of the two groups by selecting a sealed envelope . The steroid treatment group received 8 mg of dexamethasone plus 2 mL of lidocaine as a local anesthetic . The PRP treatment group received 3 mL of PRP activated with 0.45 mL of 10 % calcium gluconate . All of the patients were evaluated at the beginning of the study , and at 2 , 4 , 8 , 12 , and 16 weeks post-treatment with the Visual Analog Scale ( VAS ) , Foot and Ankle Disability Index ( FADI ) , and American Orthopedic Foot and Ankle Society ( AOFAS ) scale . RESULTS The right foot was the most frequently affected foot ( 63 % ) . The average age of the patients was 44.8 years ( range , 24 - 61 years ) . All scales used ( VAS , FADI and AOFAS ) showed that the difference was not statistically significant between the two groups . CONCLUSIONS We can conclude that the use of PRP is an effective treatment method for patients with plantar fasciitis who do not respond to conservative treatment because PRP demonstrates an efficacy equal to that of steroids . However , the cost and the time for preparation the PRP are two of the disadvantages of this treatment OBJECTIVE The aim of this study was to compare the effects of platelet-rich plasma ( PRP ) and steroid injections in patients diagnosed with plantar fasciitis . METHODS A total of 50 patients with chronic plantar fasciitis were included in the study and divided into 2 groups . In the PRP group ( n=25 ) , PRP taken from the patients ' blood was activated using calcium chloride and injected in a single dose . In the steroid group ( n=25 ) , a single dose methylprednisolone with local anesthetic injection was given . Clinical evaluation was made using the American Foot and Ankle Score ( AFAS ) and the visual analog scale ( VAS ) . RESULTS No complications were seen in any patients . Mean AFAS was 85.5 ± 4.2 at 6 weeks and 90.6 ± 2.6 at 6 months in the PRP group and 75.3 ± 4.8 and 80.3 ± 4.7 , respectively , in the steroid group ( p<0.001 ) . The difference in the mean VAS between the PRP group ( 2.4 ± 0.8 and 1 ± 0.8 ) and the steroid group ( 4 ± 1.1 and 2.6 ± 0.9 ) at the 6th week and 6th month was statistically significant ( p<0.001 ) . Changes in AFAS and VAS scores were significantly higher in the PRP group ( p<0.001 ) . CONCLUSION The application of PRP appears to be more effective than steroid injection in terms of pain and functional results in the treatment of chronic plantar fasciitis Objective : To determine the efficacy of botulinum toxin type A in chronic plantar fasciitis compared to the local injection of a corticosteroid plus local anaesthetic . Methods : Patients with a clinical diagnosis of plantar fasciitis made at least six months earlier were selected to enter a r and omized , single-blind study of treatment with injections of botulinum toxin type A or corticosteroid . There were 28 patients in each treatment group . Patients were evaluated at one month using the Foot Health Square Question naire and those with no clinical response subsequently received a second injection with the drug of the other arm of the study , creating two new treatment groups . Re-evaluation was performed at six months . Results : One month after injection there was a clear clinical improvement in both treatment groups but it was greater in the botulinum toxin group , with a significant difference for the pain item ( P = 0.069 ) , though not in other items . At six months , patients treated with botulinum toxin type A had continued to improve in all items , whereas the corticosteroid group lost part of the improvement achieved at one month ( improvement with botulinum toxin vs. corticosteroid : pain 19.10/–6.84 ( P = 0.001 ) , function 16.00/–8.80 ( P < 0.001 ) , footwear 13.48/–7.95 ( P = 0.004 ) , self-perceived foot health 25.44/–5.41 ( P < 0.001 ) . Conclusion : Botulinum toxin type A should be considered for the treatment of chronic plantar fasciitis in view of the improvement found at one month , and particularly at six months , when this treatment clearly has better results than corticosteroid injections . Further studies with larger sample s are necessary to confirm these results Background The aim of the study was to compare the efficacies of steroid injections guided by scintigraphy , ultrasonography , and palpation in plantar fasciitis . Methods A total of 35 heels of 27 patients were r and omly assigned to three steroid injection groups : palpation-guided ( pg ) , ultrasound-guided ( ug ) , and scintigraphy-guided ( sg ) . Patients were evaluated for pain intensity before the injections and at the last follow-up of 25.3 months with a 100-mm visual analog scale ( VAS ) . Results There were significant improvements in plantar fascia thickness , fat pad thickness , and VAS . Among the three groups of ug – pg , ug – sg , and pg – sg there were no statistically significant differences after treatment ( P = 0.017 , MWU = 36.5 ; P = 0.023 , MWU = 29.5 ; and P = 0.006 , MWU = 13 , respectively ) . Conclusions The ug , pg , and sg injections were effective in the conservative treatment of plantar fasciitis . We are of the opinion that steroid injections should be performed , preferably with palpation or ultrasonographic guidance Background : The objective of this study was to compare intramuscularly applied botulinum toxin A ( BTX-A ) in the gastroc-soleus complex with intralesional steroids for the treatment of plantar fasciitis . Methods : The patients were r and omly divided into 2 groups according to the treatment received . The patients were evaluated over 6 months . The evaluation scores included the Visual Analog Scale ( VAS ) , Maryl and Foot and Ankle , Foot and Ankle Disability Index ( FADI ) , and American Orthopaedic Foot and Ankle Society ( AOFAS ) score . Moreover , patients were instructed to perform plantar fascia stretching exercises over the course of the study . The final number of patients was 36 , of whom 19 received BTX-A ( 10 men and 9 women ) and 17 ( 6 men and 11 women ) received steroids . Results : When compared to patients who received steroids , the patients who received BTX-A exhibited more rapid and sustained improvement over the duration of the study . Conclusion : A combination of BTX-A and plantar fascia stretching exercises yielded better results for the treatment of plantar fasciitis than intralesional steroids . Level of Evidence : Level I , therapeutic studies A Foot Function Index ( FFI ) was developed to measure the impact of foot pathology on function in terms of pain , disability and activity restriction . The FFI is a self-administered index consisting of 23 items divided into 3 sub-scales . Both total and sub-scale scores are produced . The FFI was examined for test-retest reliability , internal consistency , and construct and criterion validity . A total of 87 patients with rheumatoid arthritis were used in the study . Test-retest reliability of the FFI total and sub-scale scores ranged from 0.87 to 0.69 . Internal consistency ranged from 0.96 to 0.73 . With the exception of two items , factor analysis supported the construct validity of the total index and the sub-scales . Strong correlation between the FFI total and sub-scale scores and clinical measures of foot pathology supported the criterion validity of the index . The FFI should prove useful for both clinical and research purpose Background : The response of chronic plantar fasciitis to any treatment is unpredictable . Autologous blood might provide cellular and humoral mediators to induce healing in areas of degeneration , the underlying pathology in plantar fasciitis . This study compared the efficacy of intralesional autologous blood with corticosteroid injection for plantar fasciitis present for more than 6 weeks . Methods : A prospect i ve , r and omized , controlled , observer-blinded study was done over a period of 6 months . Sixty-four patients were r and omly allocated to either the autologous blood or corticosteroid treatment group . All patients were assessed for the worst pain daily on visual analogue scale ( VAS ) and tenderness threshold ( TT ) at the plantar fascia origin using a pressure algometer before treatment , and at 6 weeks , 3 months , and 6 months after treatment . A p value of 0.05 was considered significant . Results : Data were complete for 61 patients . The reduction in VAS and increase in TT for both groups was significant over time ( p < 0.0001 ) . At 6 weeks and 3 months , the corticosteroid group had significantly lower VAS than the autologous blood group ( p < 0.011 and p < 0.005 , respectively ) , but the difference was not significant at 6 months . The corticosteroid group had significantly higher TT than the autologous blood group at 6 weeks , 3 months and 6 months ( p < 0.003 , p < 0.003 , p < 0.008 , respectively ) . Although the trends were different , repeated- measures F test of both VAS and TT showed no significant difference in improvement between the groups over time . Conclusions : Intralesional autologous blood injection is efficacious in lowering pain and tenderness in chronic plantar fasciitis , but corticosteroid is more superior in terms of speed and probably extent of improvement In order to evaluate the long-term results of patients treated conservatively for plantar heel pain , a telephone follow-up survey was conducted . After eliminating those patients with worker 's compensation-related complaints and those with documented inflammatory arthritides , data on 100 patients ( 58 females and 42 males ) were available for review . The average patient was 48 years old ( range 20–85 years ) . The average follow-up was 47 months ( 24–132 months ) . Clinical results were classified as good ( resolution of symptoms ) for 82 patients , fair ( continued symptoms but no limitation of activity or work ) for 15 patients , and poor ( continued symptoms limiting activity or changing work status ) in 3 patients . The average duration of symptoms before medical attention was sought was 6.1 , 18.9 , and 10 months for the three groups , respectively . The three patients with poor results all had bilateral complaints , but had no other obvious risk factors predictive of their poor result . Thirty-one patients stated that , even with the underst and ing that surgical treatment carries significant risk , they would have seriously considered it at the time medical attention was sought ; twenty-two of these patients eventually had resolution of symptoms . Although the treatment of heel pain can be frustrating due to its indolent course , a given patient with plantar fasciitis has a very good chance of complete resolution of symptoms . There is a higher risk for continued symptoms in overweight patients , patients with bilateral symptoms , and those who have symptoms for a prolonged period before seeking medical attention Background : Plantar fasciitis often leads to disability . Optimal treatment for this clinical condition is still unknown . Objective : To compare the effectiveness of wearing a full-length silicone insole with ultrasound-guided corticosteroid injection in the management of plantar fasciitis . Study design : R and omized clinical trial . Methods : Forty-two patients with chronic unilateral plantar fasciitis were allocated r and omly to have an ultrasound-guided corticosteroid injection or wear a full-length silicone insole . Data were collected before the procedure and 1 month after . The primary outcome measures included first-step heel pain via Visual Analogue Scale and Heel Tenderness Index . Other outcome measures were the Foot and Ankle Outcome Score and ultrasonographic thickness of the plantar fascia . Results : After 1 month , a significant improvement was shown in Visual Analogue Scale , Heel Tenderness Index , Foot and Ankle Outcome Score , and ultrasonographic thickness of plantar fascia in both groups . Visual Analogue Scale scores , Foot and Ankle Outcome Score pain , Foot and Ankle Outcome Score for activities of daily living , Foot and Ankle Outcome Score for sport and recreation function , and plantar fascia thickness were better in injection group than in insole group ( p < 0.05 ) . Conclusions : Although both ultrasound-guided corticosteroid injection and wearing a full-length silicone insole were effective in the conservative treatment of plantar fasciitis , we recommend the use of silicone insoles as a first line of treatment for persons with plantar fasciitis . Clinical relevance Silicone insole may be considered as a first-line treatment option in patients with plantar fasciitis Objectives : To determine if , in the short term , acetic acid and dexamethasone iontophoresis combined with LowDye ( low-Dye ) taping are effective in treating the symptoms of plantar fasciitis . Methods : A double blinded , r and omised , placebo controlled trial of 31 patients with medial calcaneal origin plantar fasciitis recruited from three sports medicine clinics . All subjects received six treatments of iontophoresis to the site of maximum tenderness on the plantar aspect of the foot over a period of two weeks , continuous LowDye taping during this time , and instructions on stretching exercises for the gastrocnemius/soleus . They received 0.4 % dexamethasone , placebo ( 0.9 % NaCl ) , or 5 % acetic acid . Stiffness and pain were recorded at the initial session , the end of six treatments , and the follow up at four weeks . Results : Data for 42 feet from 31 subjects were used in the study . After the treatment phase , all groups showed significant improvements in morning pain , average pain , and morning stiffness . However for morning pain , the acetic acid/taping group showed a significantly greater improvement than the dexamethasone/taping intervention . At the follow up , the treatment effect of acetic acid/taping and dexamethasone/taping remained significant for symptoms of pain . In contrast , only acetic acid maintained treatment effect for stiffness symptoms compared with placebo ( p = 0.031 ) and dexamethasone . Conclusions : Six treatments of acetic acid iontophoresis combined with taping gave greater relief from stiffness symptoms than , and equivalent relief from pain symptoms to , treatment with dexamethasone/taping . For the best clinical results at four weeks , taping combined with acetic acid is the preferred treatment option compared with taping combined with dexamethasone or saline iontophoresis INTRODUCTION Intractable plantar fasciitis can be a difficult condition to treat . Early results of platelet rich plasma ( PRP ) injection have been promising . We compared PRP to traditional cortisone injection in the treatment of chronic cases of plantar fasciitis resistant to traditional nonoperative management . The aim of the study was to compare the efficacy of PRP to that of Steroid at 3 , 6 and 12 months after injection . METHODS 60 heels with intractable plantar fasciitis who had failed conservative treatment were r and omised to receive either PRP or Steroid injection . All patients were assessed with the Roles-Maudsley ( RM ) Score , Visual Analogue Score ( VAS ) for pain and the American Orthopaedic Foot and Ankle Society ( AOFAS ) score . Data was collected prospect ively on the cohort , pre-treatment , at 3 , 6 and 12 months post injection and the results were compared . RESULTS Pre-injection , the two groups were well matched with no statistically significant difference . At 3 months , all three outcome scores had significantly improved from their pretreatment level in both groups . The scores in the Steroid arm were marginally better than in the PRP arm , but this difference was not statistically significant . At 6 months , there was no statistically significant difference between the two groups , though there was a trend for the PRP scores to become better than the Steroid scores . At 12 months , the RM , VAS and AOFAS scores in the PRP arm ( 1.9 , 3.3 and 88.5 ) were significantly better than the Steroid arm ( 2.6 , 5.3 and 75 ) with P values of .013 , .028 and .033 , respectively . CONCLUSIONS PRP is as effective as Steroid injection at achieving symptom relief at 3 and 6 months after injection , for the treatment of plantar fasciitis , but unlike Steroid , its effect does not wear off with time . At 12 months , PRP is significantly more effective than Steroid , making it better and more durable than cortisone injection Objective : To compare the efficacy of low-energy extracorporeal shock wave therapy ( ESWT ) and intralesional corticosteroid injection ( CSI ) for the treatment of plantar fasciopathy present for at least 6 weeks . Design : A prospect i ve , r and omized , controlled , observer-blinded study over a period of 12 months . Setting : Primary care and hospital setting . Patients : A total of 132 patients were enrolled in the study , and 125 completed the study . Nineteen nonr and omized patients acted as a surrogate control group . Interventions : All patients performed a st and ardized Achilles tendon and plantar fascia stretching program . The patients were r and omly allocated to either treatment group A or B. Group A received a single CSI , while group B were referred for a course of low-dose ESWT comprising 3 treatments over a period of 3 weeks . Group C consisted of 19 nonr and omized patients who performed the st and ardized stretching program only . Main Outcome Measurements : The worst daily pain recorded on a visual analogue scale ( VAS ) , and the tenderness at the plantar fascia insertion as determined by an algometer . These measures were recorded immediately prior to the commencement of treatment and 3 months and 12 months posttreatment . Results : With regard to VAS pain scores , values for the CSI ( 1.48 ; 0 - 7 ) were significantly lower than both ESWT ( 3.69 ; 0 - 8 ) , and controls ( 3.58 ; 2 - 5 ) at 3 months . At 12 months , VAS scores for CSI ( 0.84 ; 0 - 7 ) and ESWT ( 0.84 ; 0 - 4 ) were both significantly lower than controls ( 2.42 ; 1 - 4 ) . The tenderness values at 3 months were significantly higher for CSI ( 9.42 ; 7 - 11 ) than both ESWT ( 6.72 ; 4 - 11 ) and controls ( 7.63 ; 6 - 9 ) . P < 0.05 was used throughout . Conclusions : Corticosteroid injection is more efficacious and multiple times more cost-effective than ESWT in the treatment of plantar fasciopathy that has been symptomatic for more than 6 weeks A r and omized , prospect i ve study was conducted to compare the individual effectiveness of three types of conservative therapy in the treatment of plantar fasciitis . One hundred three subjects were r and omly assigned to one of three treatment categories : anti-inflammatory , accommodative , or mechanical . Subjects were treated for 3 months , with follow-up visits at 2 , 4 , 6 , and 12 weeks . For the 85 patients who completed the study , a statistically significant difference was noted between groups , with mechanical treatment with taping and orthoses proving to be more effective than either anti-inflammatory or accommodative modalities The aim of this study was to compare the effect of extracorporeal shockwave therapy ( ESWT ) in patients with chronically painful proximal plantar fasciitis with a conventional conservative treatment consisting of nonsteroidal anti-inflammatory drugs , heel cup , orthoses and /or shoe modifications , local steroid injections and electrotherapy . Forty-seven patients ( 49 feet ) with a previously unsuccessful conservative treatment of at least six months were r and omized to two groups . Treatment of Group 1 ( 25 heels ) started immediately with three sessions of ESWT ( 3000 shockwaves/session of 0.2 mJ/mm2 ) at weekly intervals . In the patients of Group 2 ( 24 heels ) treatment was continued for 12 weeks . After this period they were treated using the protocol of Group 1 . No significant difference of pain and walking time after further non-ESWT treatment ( three months ) was seen . Six months after ESWT pain decreased by 64 % to 88 % on the visual analog scale ( VAS ) and the comfortable walking time had increased significantly in both groups OBJECTIVES Plantar fasciitis is a self-limiting condition , but can be painful and disabling . Among the different treatments which exist , corticosteroid injections are effective and popular . Extracorporeal shock wave therapy ( ESWT ) is another treatment modality used for resistant conditions . In this study , the authors evaluated the efficacy of radial ESWT versus corticosteroid injections in the treatment of chronic plantar fasciitis . DESIGN R and omized clinical trial . SETTING Physical medicine and rehabilitation research center in a university hospital . SUBJECTS Forty patients with plantar fasciitis who did not respond to conservative treatment . METHODS Patients were allocated to radial ESWT with 2000 shock waves/session of 0.2 mJ/mm(2 ) ( n = 20 ) or local methylprednisolone injections ( n = 20 ) . Pain in the morning and during the day based on a visual analog scale ( VAS ) , functional abilities using the foot function index ( FFI ) , and satisfaction were evaluated before treatment and at 4 and 8 weeks after treatment . RESULTS Patients ( average age : 42.1± 8.20 ) received five sessions of ESWT or single steroid injection . Changes in the VAS in morning and during the day and the FFI throughout the study period were significant in both groups ( P < 0.001 ) . ESWT group had a higher reduction in VAS in morning and better function in FFI , but these changes were insignificant statistically [ FFI decreased to 19.65 ± 21.26 points ( 67.4 % improvement ) in ESWT vs 31.50 ± 20.53 points ( 47.7 % ) in injection group at week 8 , P = 0.072 ) ] . Good or excellent results in the opinions of patients were achieved in 55 % of ESWT and 30 % of corticosteroid injection groups ( P = 0.11 ) . CONCLUSION Both interventions caused improvement in pain and functional ability 2 months after treatment . Although inter-group differences were not significant , the FFI was improved more with ESWT and patients were more satisfied with ESWT , thus shockwave therapy seems a safe alternative for management of chronic plantar fasciitis Introduction : The American Orthopaedic Foot and Ankle Society ( AOFAS ) Ankle-Hindfoot Score has been under recent scrutiny . The Foot and Ankle Outcome Score ( FAOS ) is an alternative subjective survey , assessing outcomes in 5 subscales . It is vali date d for lateral ankle instability and hallux valgus patients . The aim of our study was to vali date the FAOS for assessing outcomes in flexible adult acquired flatfoot deformity ( AAFD ) . Methods : Patients from the authors ’ institution diagnosed with flexible AAFD from 2006 to 2011 were eligible for the study . In all , 126 patients who completed the FAOS and the Short-Form 12 ( SF-12 ) on the same visit were included in the construct validity component . Correlation was deemed moderate if the Spearman ’s correlation coefficient was .4 to .7 . Content validity was assessed in 63 patients by a question naire that asked patients to rate the relevance of each FAOS question , with a score of 2 or greater considered acceptable . Reliability was measured using intraclass correlation coefficients ( ICCs ) in 41 patients who completed a second FAOS survey . In 49 patients , preoperative and postoperative FAOS scores were compared to determine responsiveness . Results : All of the FAOS subscales demonstrated moderate correlation with 2 physical health related SF-12 domains . Mental health related domains showed poor correlation . Content validity was high for the Quality of Life ( QoL ; mean 2.26 ) and Sports/Recreation subscales ( mean 2.12 ) . All subscales exhibited very good test – retest reliability , with ICCs of .7 and above . Symptoms , QoL , pain , and daily activities ( ADLs ) were responsive to change in postoperative patients ( P < .05 ) . Conclusion : This study has vali date d the FAOS for AAFD with acceptable construct and content validity , reliability , and responsiveness . Given its previous validation for patients with ankle instability and hallux valgus , the additional findings in this study support its use as an alternative to less reliable outcome surveys . Level of Evidence : Level II , prospect i ve comparative study Background : Chronic plantar fasciitis is a common orthopedic condition that can prove difficult to successfully treat . In this study , autologous platelet-rich plasma ( PRP ) , a concentrated bioactive blood component rich in cytokines and growth factors , was compared to traditional cortisone injection in the treatment of chronic cases of plantar fasciitis resistant to traditional nonoperative management . Methods : Forty patients ( 23 females and 17 males ) with unilateral chronic plantar fasciitis that did not respond to a minimum of 4 months of st and ardized traditional nonoperative treatment modalities were prospect ively r and omized and treated with either a single ultrasound guided injection of 3 cc PRP or 40 mg DepoMedrol cortisone . American Orthopedic Foot and Ankle Society ( AOFAS ) hindfoot scoring was completed for all patients immediately prior to PRP or cortisone injection ( pretreatment = time 0 ) and at 3 , 6 , 12 , and 24 months following injection treatment . Baseline pretreatment radiographs and MRI studies were obtained in all cases to confirm the diagnosis of plantar fasciitis . Results : The cortisone group had a pretreatment average AOFAS score of 52 , which initially improved to 81 at 3 months posttreatment but decreased to 74 at 6 months , then dropped to near baseline levels of 58 at 12 months , and continued to decline to a final score of 56 at 24 months . In contrast , the PRP group started with an average pretreatment AOFAS score of 37 , which increased to 95 at 3 months , remained elevated at 94 at 6 and 12 months , and had a final score of 92 at 24 months . Conclusions : PRP was more effective and durable than cortisone injection for the treatment of chronic recalcitrant cases of plantar fasciitis . Level of Evidence : Level I , prospect i ve r and omized comparative series Objectives : To compare the effectiveness of oral nonsteroidal antiinflammatory drugs ( NSAIDs ) and locally injectable steroid ( methylprednisolone ) in the treatment of plantar fasciitis . Material s and Methods : One hundred and twenty subjects with unilateral plantar fasciitis were recruited and r and omly allocated to two study groups . Group I ( NSAIDs group ) ( n=60 ) received oral tablet diclofenac ( 50 mg ) and paracetamol ( 500 mg ) twice a day ( BD ) along with tab . ranitidine 150 mg BD . Group II ( injectable steroid group ) ( n=60 ) received injection of 1 ml of methylprednisolone ( Depomedrol ) ( 40 mg ) and 2 ml of 0.5 % bupivacaine into the inflammed plantar fascia . Pain intensity was measured using 10 cm visual analog scale ( VAS ) . Subjects were evaluated clinical ly before , and 1 week , 2 weeks , 4 weeks , and 8 weeks ( 2 months ) after the initiation of treatment in both the groups . The outcome was assessed in terms of VAS score and recurrence of the heel pain . Statistical Analysis Used : “ Z ” test and Chi-square test were used wherever applicable . Results : Pain relief was significant after steroid injection ( P<0.001 ) and the improvement was sustained . The recurrence of heel pain was significantly higher in the oral NSAIDS group ( P<0.001 ) . Conclusion : Local injection of steroid is more effective in the treatment of plantar fasciitis than oral NSAIDs |
13,806 | 24,151,011 | Evidence regarding NB-UVB versus bath PUVA is also inconsistent .
Re-NB-UVB and re-PUVA are similarly effective for treating people with CPP or GP .
In practice , NB-UVB may be more convenient to use since exogenous photosensitiser is not required before phototherapy .
NB-UVB is considered ineffective for PPP in clinical practice , and a small RCT did not detect a statistically significant difference between NB-UVB and topical PUVA for clearing PPP . | BACKGROUND The most commonly used types of phototherapy for treating psoriasis are narrow-b and ultraviolet B ( NB-UVB ) ; broad-b and ultraviolet B ( BB-UVB ) , which includes selective ( delivering radiation with a wavelength range of 305 to 325 nm ) and conventional BB-UVB ( 280 to 320 nm ) ; and psoralen ultraviolet A photochemotherapy ( oral or bath PUVA ) .
There is substantial controversy regarding their efficacy when compared with each other .
OBJECTIVES To assess the effects of narrow-b and ultraviolet B phototherapy versus broad-b and ultraviolet B or psoralen ultraviolet A photochemotherapy for psoriasis . | OBJECTIVE To compare the therapeutic effectiveness of daily exposure to narrowb and ( NB ) UV-B vs broadb and ( BB ) UV-B with and without tar . DESIGN Half-body exposures to NB UV-B or BB UV-B were given daily for 4 weeks in this comparative treatment study . Narrowb and UV-B was delivered from TL-01 fluorescent bulbs and BB UV-B from conventional bulbs in the same phototherapy cabinet . Narrowb and UV-B was compared using a paired treatment approach to BB UV-B above the waist and to BB UV-B with tar ( Goeckerman treatment ) below the waist . SETTING General clinical research center of a university hospital inpatient unit . PATIENTS Twenty-two patients with moderate-to-severe plaque-type psoriasis completed the study . MAIN OUTCOME MEASURES Clinical efficacy was measured weekly using psoriasis severity scoring . Therapeutic outcomes after 4 weeks were compared in paired biopsy sample s from treated lesions using objective histopathological measures ( quantitative reduction in epidermal acanthosis and keratin 16 expression ) . RESULTS Clinical resolution of psoriasis was achieved on 86 % of paired sites treated with NB UV-B vs 73 % treated with BB UV-B. Histopathological resolution of epidermal hyperplasia ( marked by keratin 16 expression ) was achieved in 88 % of lesions treated with NB UV-B vs 59 % treated with BB UV-B. Epidermal acanthosis was reduced more completely by NB UV-B treatment . Clinical resolution of psoriatic lesions occurred more rapidly following NB UV-B treatment , with some patients achieving complete resolution after 2 to 3 weeks of treatment . CONCLUSIONS Narrowb and UV-B offers a significant therapeutic advantage over BB UV-B in the treatment of psoriasis , with faster clearing and more complete disease resolution . The erythema response to NB UV-B treatment was significantly more intense and persistent compared with BB UV-B. Considerably more necrotic keratinocytes were observed in histopathological sections of skin treated with NB UV-B after a single 2.0-minimum erythema dose exposure . Treatment should be coupled with obligate minimum erythema dose testing to NB UV-B and close clinical observation during dose increases BACKGROUND A narrow-b and UVB lamp ( Philips TL 01 ) emitting a peak of approximately 311 nm was developed to improve the phototherapy for psoriasis . Only a few studies have been performed with promising results . OBJECTIVE The therapeutic efficacy of the Philips TL 01 lamp in a new 100 W version was compared with conventional broad-b and lamps ( Sylvania UV 6 ) in a controlled trial . METHODS Twenty-three patients with psoriasis were treated with half-body exposures from the different UVB sources . The rate of clearing was monitored by estimation of the Psoriasis Area and Severity Index . All patients used emollients ; excessive scaling was removed with salicylic acid in yellow petrolatum . In 13 patients dithranol in a modified Ingram regimen was added . In most cases the study was discontinued once a difference between the two sides was evident . RESULTS In 20 of 23 cases the TL 01 lamp proved to be significantly more effective than the conventional source . Application of dithranol provided a substantial additional therapeutic effect . With the high-intensity TL 01/100W bulbs , exposure times were comparable to broad-b and UVB phototherapy . CONCLUSION The therapeutic efficacy of Philips TL 01/100W and its practicability for psoriasis phototherapy have been demonstrated The efficacy of trimethylpsoralen bath PUVA and UVB TL01 were compared in chronic plaque psoriasis . Patients were r and omly assigned to receive UVB TL01 on one side and bath PUVA on the contra-lateral side . Altogether 17 patients received treatments and 15 completed the trial . The decrease in the PASI score was greater with UVB TL01 than PUVA . At the end of the treatment period , the difference was highly significant ( p < 0.001 ) . The difference was already significant at week 3 ( p = 0.014 ) . The relative median decrease in the PASI score was 77 % ( 24 - 100 % ) with UVB and 45 % ( 8 - 100 % ) with PUVA . The median cumulative UVB dose was 39.92 ( range 13.95 - 81.56 ) J/cm2 and the corresponding UVA dose was 8.06 ( range 3.31 - 12.51 ) J/cm2 . All patients relapsed within 4 months . Narrowb and UVB improved psoriasis clinical ly and statistically more efficiently than trimethylpsoralen bath PUVA , and UVB was better tolerated Forty patients with pustulosis palmaris et plantaris were treated with tetracycline 250 mg twice daily or with placebo , in a double‐blind trial . In twenty‐eight patients the lesions were confined to the palms and soles , whereas twelve had psoriatic lesions affecting other parts of the skin and /or nails . Radiological signs of focal infection were found in eighteen patients . In thirty‐five patients positive bacteriological culture from pustules was obtained , the most common strain being Staphylococcus albus Twenty-nine patients with psoriasis took part in a study which compared the therapeutic effect of Philips TL12 with a new narrow-b and UVB lamp ( Philips TL01 ) . The patients were treated on an out-patient basis and treatment were given 3 - 5 times weekly for a maximum of 8 weeks . The study was conducted in a r and omized left-right double-blind fashion . The total score on the TL01-side decreased rather more than on the TL12-side . Eleven patients preferred the TL01 lamp and one the TL12-side , whereas 17 patients had no preference . One of the drawbacks with the new lamp is that radiation times are almost doubled INTRODUCTION Studies carried out to date comparing treatment with PUVA baths and narrow-b and UVB ( NBUVB ) in psoriasis show that better results are obtained with NBUVB . Certain features of the protocol s may interfere with the results . MATERIAL AND METHODS Prospect i ve study in a psoriasis unit , with treatment assigned according to availability . Of 167 patients with psoriasis plaques , 32 received PUVA baths ( photosensitizer 8-methoxypsoralen at a concentration of 2.6 mg/l ) and 135 received NBUVB radiation . A clearing rate of over 70 % was considered a good response . The data were described and compared between the two groups , including multivariate analysis techniques , in order to statistically control the effects of gender , number of sessions necessary for success , minimum phototoxic dose and minimum erythema dose . RESULTS A good response was obtained in 87.5 % of the cases with PUVA baths ( 95 % CI : 71.0 - 96.5 ) and in 87.4 % of the cases with NBUVB ( 95 % CI : 80.6 - 92.5 ) . No significant differences were found in the success and ab and onment percentages . Among the patients who responded to the treatment , no differences were found in the number of sessions or in the cumulative dose . Gender , cumulative dose or minimum phototoxic dose and minimum erythema dose values were not associated with the response to the treatments either . CONCLUSIONS With psoriasis plaques , similar response percentages can be expected with both treatments , using the proposed protocol s. The response is regardless of gender , cumulative dose and minimum phototoxic dose and minimum erythema dose values OBJECTIVE This was a double-blind , r and omized multicentre trial comparing efficacy and safety of brivudin ( 125 mg , once a day ) and famciclovir ( 250 mg , three times a day ) , both given orally for 7 days , in the treatment of herpes zoster . METHODS A total of 2027 immunocompetent zoster patients > or=50 years with zoster-related pain at presentation were included . Outcome measures embraced prevalence of postherpetic neuralgia ( PHN ) , defined as at least moderate pain 3 months after treatment initiation , duration of PHN , prevalence and duration of zoster-associated pain ( ZAP ) , duration of vesicle formation and rash healing . RESULTS The prevalence of PHN at month 3 was 11.3 % with brivudin and 9.6 % with famciclovir [ per- protocol ( PP ) population ] . Equivalence of the two drugs could be demonstrated ( P=0.01 , PP and intention-to-treat analysis ) . The median duration of PHN was 46.5 days with brivudin and 58 days with famciclovir ( P=0.54 , PP analysis ) . Prevalence and duration of ZAP did not differ significantly between treatment groups . The prevalence of PHN was higher in patients > or=65 years ( brivudin : 16.4 % , famciclovir : 16.4 % ) , and in patients with severe rash ( brivudin : 13.4 % , famciclovir : 15.7 % ) , without significant differences between treatment groups . In patients > or=65 years , median duration of PHN was shorter with brivudin than with famciclovir ( 39.5 vs. 57.5 days ) , although the difference was not statistically significant . The two drugs had equivalent efficacy in being able to accelerate the stop of vesicle formation , and lesion healing . Adverse events were similar in nature and prevalence among groups . CONCLUSIONS The study demonstrated equivalent efficacy of brivudin and famciclovir in the treatment of herpes zoster regarding the prevention of chronic pain and the resolution of signs and symptoms of acute herpes zoster . Compared with famciclovir , brivudin provides equivalent efficacy and safety at a more convenient once-daily dose schedule BACKGROUND Although PUVA treatment of psoriasis is more effective than conventional or broad-b and UVB phototherapy , two small studies have suggested that narrow-b and or TL-01 phototherapy may have a therapeutic effect equal to PUVA . If confirmed , this would be of considerable importance as TL-01 therapy is likely to be considerably safer in the long term than PUVA . OBJECTIVE The purpose of this study was to compare PUVA with narrow-b and ( TL-01 ) phototherapy in psoriasis . METHODS We studied 100 patients with plaque-type psoriasis who were r and omly allocated to twice-weekly treatment with PUVA or narrow-b and UVB . RESULTS Clearance of psoriasis was achieved in a significantly greater proportion of patients treated with PUVA ( 84 % ) than with TL-01 ( 63 % ) ( P = .018 ) , and with significantly fewer treatments ( median number of treatments for clearance with PUVA , 16.7 ; with TL-01 , 25.3 ; P = .001 ) . Only 12 % of those treated with TL-01 were clear of psoriasis 6 months after finishing treatment compared with 35 % for PUVA ( P = .002 ) . CONCLUSION When given twice weekly , PUVA is more effective for psoriasis than narrow-b and UVB phototherapy Continued prospect i ve study of the 1,380 patients enrolled in the PUVA study for 10 years after first exposure to PUVA demonstrates a strong association between cumulative exposure to PUVA and an increased risk of squamous cell carcinoma of the skin . For tumors occurring at least 58 months after first treatment , after adjustment for age , sex , and area of residence , we observed that patients with more than 260 treatments had an 11-fold increase in risk compared to patients who had received 160 or fewer treatments during the same interval ( P less than 0.01 ) . Comparable increases in relative risk were noted in patients of all skin types , irrespective of prior ionizing radiation exposure . We also noted a modest dose-dependent increase in the risk for the development of basal cell carcinoma for patients who received an excess of 200 treatments compared to those who had received fewer than 160 treatments within the same time period ( P less than 0.05 ) . Tumors detected in our cohort exhibit biologic behavior similar to non-melanoma skin cancers associated with sun exposure . Careful monitoring and early detection should limit the morbidity associated with these tumors A bilateral comparison study of the therapeutic effects of broad-b and ultraviolet ( UBV ) ( FS-40 Sunlamp bulbs ) radiation versus UVB radiation plus methoxsalen was conducted in patients with psoriasis . Ten patients were given up to 30 exposures to the two treatments on paired , similarly affected limbs . There was no detectable difference in the response of limbs treated with UVB plus methoxsalen versus UVB phototherapy alone although all patients did show a therapeutic response . Other areas of the body treated with methoxsalen and broad-b and UVA radiation ( PUVA bulbs ) responded more rapidly and to a greater extent than areas exposed to UVB radiation OBJECTIVE To compare the efficacy of oral psoralen-UV-A ( PUVA ) therapy with that of narrowb and UV-B ( NB-UVB ) therapy in patients with chronic plaque psoriasis . DESIGN Double-blind r and omized study . SETTING Phototherapy unit in a university hospital . Patients Ninety-three patients with chronic plaque psoriasis . Interventions Twice-weekly NB-UVB or PUVA therapy , starting at 70 % of the minimum phototoxic or erythema dose , with 20 % incremental increases . Patients were treated until clearance , up to a maximum of 30 sessions ; those with clearance were followed up until relapse or for 12 months . MAIN OUTCOME MEASURES Proportion of patients achieving clearance , number of treatments to clearance , and , among those with clearance , the proportion remaining in remission at 6 months . RESULTS Patients with skin types V and VI had a lower rate of clearance than those with skin types I through IV ( 24 % vs 75 % ; P = .001 ) . In patients with skin types I through IV , PUVA was significantly more effective than NB-UVB at achieving clearance ( 84 % vs 65 % ; P = .02 ) . The median number of treatments to clearance was significantly lower in the PUVA group ( 17.0 vs 28.5 ; P<.001 ) . More patients treated with PUVA vs NB-UVB were reported to have erythema at some stage during treatment ( 49 % vs 22 % ; P = .004 ) , although this difference may have been due to ascertainment bias . Six months after the cessation of therapy , 68 % of PUVA-treated patients were still in remission vs 35 % of NB-UVB-treated patients . Conclusion Compared with NB-UVB , PUVA achieves clearance in more patients with fewer treatment sessions and results in longer remissions OBJECTIVE To compare the efficacy of narrowb and UV-B ( TL-01 ) phototherapy with oral 8-methoxypsoralen photochemotherapy ( 8-MOP psoralen-UV-A [ PUVA ] ) in patients with chronic plaque psoriasis ( CPP ) . DESIGN Open , r and omized , controlled study . SETTING Phototherapy unit in a dermatology hospital . PATIENTS Fifty-four patients with CCP . INTERVENTIONS Patients received whole-body threshold erythemogenic dose of either 3-times weekly TL-01 or twice-weekly oral 8-MOP PUVA , based on minimal erythema or phototoxic doses . Patients were treated until completely clear . OUTCOME MEASURES Number of treatments to clear , number of days in treatment , number of days in remission , and adverse effects of both therapies were assessed . RESULTS Forty-five patients completed the study . Those in the PUVA group required significantly fewer treatments to clear ( P = .03 ) . There was no significant difference in the number of days to clear or number of days in remission . A similar percentage of patients in the TL-01 and PUVA groups developed minimal perceptible erythema , showing that the regimens were equally erythemogenic . Asymptomatic , well-defined erythema occurred only in the PUVA group . Pruritus and polymorphic light eruption occurred equally in both groups , but only patients in the PUVA group developed nausea . CONCLUSION Narrowb and UV-B phototherapy , used 3 times weekly , is as effective for the treatment of CPP as oral 8-MOP PUVA used twice weekly BACKGROUND Both bath psoralen plus ultraviolet A ( PUVA ) and oral PUVA with 8-methoxypsoralen ( 8-MOP ) have been successfully used for the treatment of recalcitrant palmoplantar psoriasis . This trial was design ed to assess the efficacy and side effects of the different treatment modalities in a r and omized half-side comparison . METHODS Eight patients with moderate-to-severe psoriasis on soles ( n = 6 ) and /or palms ( n = 8) were r and omly assigned to receive bath PUVA treatment on one side and oral PUVA on the other . Initial treatment dose was 50 % of the minimal phototoxic dose evaluated for bath PUVA and oral PUVA . Treatment was given three times a week for 4 weeks . Before treatment and every week a severity index ( SI ) was assessed by summing the scores of erythema , infiltration , scaling and vesicles evaluated on a scale from 0 to 4 . After 4 weeks of treatment the half-side trial was finished and the treatment was continued on both sides with the more effective treatment regimen . RESULTS Both bath PUVA and oral PUVA achieved a reduction of the mean initial SI from 5.9 ( 95 % confidence intervals ( CI ) 4.5 - 8.0 ) to 3.3 ( 1.8 - 6.0 ) ( 44 % SI reduction , P < 0.005 , Student 's paired t-test ) and 6.0 ( 5.0 - 7.8 ) to 2.9 ( 1.8 - 4.0 ) ( 52 % SI reduction ; P < 0.005 ) , respectively . The statistical comparison of the entire 4-week study period revealed a significant better effect in lesions treated with oral PUVA compared with bath PUVA ( P = 0.033 ) . However , at 4 weeks , there was no significant difference between the achieved SI reduction of oral PUVA and bath PUVA . Systemic side effects ( nausea and /or dizziness ) were only observed after oral PUVA . CONCLUSION This study gives evidence that in the first 4 treatment weeks oral PUVA is slightly more effective than bath PUVA but the former has more systemic side effects BACKGROUND Psoralen UV-A ( PUVA ) is an established therapy for psoriasis , but there is a well-documenated risk of melanoma and nonmelanoma skin cancer . Narrow-b and Ultraviolet-B ( NBUVB ) therapy has a lower carcinogenic risk , has equal therapeutic potential and is considerably safe in the long term than PUVA . AIM The aim of present study was to compare the efficacy and side-effects of PUVA and NBUVB in chronic plaque psoriasis . METHODS Sixty patients of chronic plaque psoriasis were taken up for the study and were r and omly divided into two groups of 30 each . They were well matched in terms of age , sex , psoriasis extent and pretreatment psoriasis area severity index ( PASI ) scoring . One group was treated with twice-weekly narrow-b and UV-B ( TL-01 ) phototherapy and the other group received twice-weekly oral 8-Methoxsalen PUVA for a period of 3 months . RESULTS Both the groups achieved > 75 % reduction in the PASI score or complete clearance at the end of 3 months , but PUVA group patients required significantly fewer number of treatment sessions and fewer number of days to clear the psoriasis as compared to the NBUVB group , while the mean cumulative clearance dose and adverse effects were significantly lower in the NBUVB group . CONCLUSION We concluded that PUVA group patients achieved a faster clearance , but the adverse effects were significantly lower in the NBUVB group In a left‐right comparative study , the Philips TL‐01 sunlamp , a new UVB fluorescent lamp , was evaluated in 15 patients with symmetrical psoriasis . One half of the body was treated in a cabin containing TL‐01 lamps , and the other half in a cabin containing TL‐12 lamps . The patients were treated three times/week , and the study was conducted in a r and omized , double‐blind fashion . The percentage response of psoriatic lesions was determined on the tenth and twentieth exposures . The therapeutic effect of the TL‐01 lamps was superior to that of the TL‐12 lamps , and treatment was better tolerated , particularly with regard to episodes of burning . This new lamp appears to provide more effective and safer phototherapy for psoriasis UVB is widely used to treat psoriasis . Conventional broadb and UVB lamps are less effective than narrowb and UVB lamps , which have an emission peak at 311 nm . The long-term safety of narrowb and UVB phototherapy is uncertain . " Selective " broadb and UVB lamps , which have little emission < 290 nm , are also available , but have not been adequately compared to narrowb and UVB lamps . We performed a r and omized comparison of narrowb and UVB ( TL-01 lamps ) and selective broadb and UVB ( UV6 lamps ) in 100 patients with psoriasis . The median number of exposures for clearance was 28.4 for TL-01 and 30.4 for UV6 ( ratio of the medians 0.93 ; 95 % confidence interval ( CI ) 0.80 , 1.09 ; P=0.39 ) . No significant difference was found in the proportion of patients achieving clearance : TL-01 56 % , UV6 40 % ( odds ratio for clearance with TL-01 relative to UV6 was 2.00 ( 95 % CI 0.87 , 4.62 ) , P=0.10 ) . Side effects , including the development of erythema during phototherapy , were similar for the two lamp types . Risk estimates based on the human photocarcinogenesis action spectrum predict that narrowb and UVB lamps will be 50 % more carcinogenic for equal erythemal doses than selective broadb and lamps ( UV6 ) . As these two lamp types appear to be of similar efficacy , phototherapy using a selective broadb and source may be a safer option than use of narrowb and UVB One hundred eighty-three patients with psoriasis were treated with UV-B irradiation or oral methoxsalen plus longwave UV light ( PUVA ) . Patients treated with PUVA , in the initial and maintenance period , achieved in general a higher therapeutic score ( 95 % to 100 % clearance ) than those receiving UV-B therapy . However , taking 80 % to 100 % improvement as criterion , no difference was found between initial UV-B and PUVA therapy , if less than 50 % of the skin surface was affected by psoriasis . If more than 50 % of the skin was involved , PUVA was better than UV-B therapy . The maintenance treatment frequency for the UV-B-treated patients for more than a year seemed to be higher than for PUVA-treated patients . A positive correlation was found between response to sunbathing ( question naire survey ) and the response to UV-B phototherapy . An extra UV-B treatment to the leg lesions appeared useless Summary Background In 1991 , consensus guidelines recommended psoralen plus ultraviolet A photochemotherapy ( PUVA ) for those requiring second‐line therapy for psoriasis . Narrowb and ( TL‐01 ) UVB has since become more widely available , replacing the less effective broadb and sources Summary Forty‐five patients with extensive chronic plaque or guttate psoriasis were treated with either narrowb and ( TL‐01 ) phototherapy , etretinate TL‐01 combination therapy ( re‐TL‐01 ) or etretinate and PUVA ( re‐PUVA ) ( 15 patients in each group ) . Re‐PUVA was the most effective therapy with 100 % satisfactory clearance rate . TL‐01 monotherapy had an 80 % success rate ; the relapse rate compared favourably with re‐PUVA ( 50 % in remission after 6 months ) . In the etretinate‐TL‐01 group , there was a 93 % success rate and a one‐third reduction in the total irradiation dose ( 8.0 J/cm2 vs , 12.7 J/cm2 ) but the relapse rate was higher , only 33 % remaining in remission after 6 months We have compared the therapeutic effectiveness of a new UVB fluorescent sunlamp , the Philips TL‐01 lamp , which emits a narrow peak around 311–312 nm , with the currently used Philips TL‐I2 lamp , in 10 patients with psoriasis . We also compared the tumour inducing capacity of the two lamps in hairless mice 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 The combination of retinoids with phototherapy enhances the efficacy of phototherapy and reduces the cumulative ultraviolet dose and duration of the therapy needed to treat chronic plaque psoriasis . Although TL-01 phototherapy has been used widely , there are few data about the effectiveness of the combination of acitretin with TL-01 in treatment of the disease . The aim of this study was to compare acitretin-narrow-b and TL-01 phototherapy with acitretin-psoralen plus ultraviolet A ( acitretin-PUVA ) in psoriasis . We studied 60 patients with moderate to severe plaque psoriasis who were r and omly allocated to three times weekly treatment acitretin-narrow-b and TL-01 or acitretin-PUVA . The efficacy of treatments was assessed using the Psoriasis Area and Severity Index by a blinded observer . Clearance of psoriasis was achieved in 56.6 % of patients treated with acitretin-narrow-b and TL-01 and in 63.3 % of those treated with acitretin-PUVA . All of these patients remained clear of psoriasis 3 months after finishing the treatments . Mucocutaneous side-effects , such as dry lips and mouth , were the most common complaints in both groups . In conclusion , acitretin-narrow-b and TL-01 is an effective and well-tolerated treatment for moderate to severe plaque psoriasis , with a therapeutic effect equal to that of acitretin-PUVA |
13,807 | 29,044,054 | Intracameral/intravitreal antibiotics reduce the risk of endophthalmitis in open globe injuries ; although , there was no improvement in the visual acuity . | Traumatic endophthalmitis is a devastating condition that can occur following an open globe injury and result in loss of vision .
The use of prophylactic antibiotics is empirical as most surgeons fear complications associated with the same .
No systematic review has been performed in English on the role of intravitreal/intracameral antibiotics in preventing traumatic endophthalmitis . | BACKGROUND AND OBJECTIVE To evaluate predictors of visual outcomes and microbial profile in endophthalmitis . PATIENTS AND METHODS This was a prospect i ve , interventional case series at a tertiary eye care center . Of the 207 patients included , 83 had post-cataract surgery endophthalmitis ( PCE ) , 84 had post-traumatic endophthalmitis ( PTE ) , and 16 had endogenous endophthalmitis . Vitreous sample s were evaluated for microbial profile , and all patients received similar empirical antibiotic therapy . Main outcome measures were good visual acuity , defined as better than 20/400 , and microbial profile with drug resistance . RESULTS Final visual acuity better than 20/400 was seen in 88 % patients previously treated with intravitreal antibiotics ( P < .001 ) , 89 % with presenting vision of less than 3.3 LogMAR units ( P < .001 ) , 61 % without retinal detachment ( RD ) ( P < .001 ) , 58 % without retained intraocular foreign body ( RIOFB ) ( P = .007 ) , 88 % without extensive media haze ( P = .007 ) , 71 % of culture-negative patients ( P = .007 ) , and 65 % with gram-positive bacteria ( P = .03 ) . On multivariate analysis , presenting visual acuity of less than 3.3 LogMAR units was found to have the highest adjusted odds ratio , 26.28 ( 95 % CI , 9.13 - 75.6 ) , for better visual outcome . Culture positivity was nearly 37 % . Gram-positive bacteria were the most common in both PCE ( 90 % ) and PTE ( 55 % ) groups , whereas hyphae form fungus was the most common organism grown in endogenous endophthalmitis ( 50 % ) ( P < .001 ) . In patients without extensive media haze , hyphae form fungus was the most common grown organism ( 42 % ) ( P = .03 ) . PTE was predominant ( 60 % ) in the patients with antibiotic resistance . CONCLUSIONS Presenting visual acuity better than h and motions close to face is the single most common indicator of good visual prognoses . Fungal infections are associated with RD , RIOFB , trauma , and absence of extensive media haze . Microbial resistance may be an important concern in PTE patients . [ Ophthalmic Surg Lasers Imaging Retina . 2016;47:991 - 998 . ] Purpose : The effectiveness of an intraocular injection of combined gentamicin and clindamycin in the prevention of acute posttraumatic bacterial endophthalmitis following penetrating ocular injuries was evaluated in a prospect i ve , double-masked , r and omized pilot study . Methods : Sixty eyes of 60 patients with penetrating ocular injuries were treated at a tertiary care hospital . Following primary repair , the eyes were r and omized in two groups . Group 1 , the antibiotic injection group ( cases ) , was given an intracameral or intravitreal injection of 0.1 mL antibiotic ( 40 μg gentamicin and 45 μg clindamycin ) . Group 2 ( balanced saline solution [ BSS ] injection group [ controls ] ) received intracameral or intravitreal injection of 0.1 mL BSS . All patients received st and ard prophylactic antibiotic therapy ( systemic , subconjunctival , and topical ) . Result : Although the overall incidence of acute posttraumatic bacterial endophthalmitis was 6.6 % ( 4 eyes ) , the results of three cultures were negative . All endophthalmitis cases occurred in the BSS injection group ; however , there was no statistically significant difference between case and control groups ( p = 0.11 ) . The incidence rate for those with retained intraocular foreign bodies was 13.3 % and for those without foreign bodies was 4.4 % . No retinal toxicity was detected . Conclusion : Intraocular injection of gentamicin and clindamycin in addition to the other methods of prophylaxis may be an effective modality in the prevention of posttraumatic endophthalmitis . Early results suggest that these antibiotics may have a role as adjunct therapy to primary repair of injured globes without significant side effects at the dosage used PURPOSE To determine the efficacy of prophylactic intravitreal antibiotics in reducing the incidence of endophthalmitis after trauma . METHODS This was a prospect i ve , r and omised , case control study of 70 consecutive patients with open globe injury . The patients were prospect ively r and omised into group I ( 32 eyes ) and group II ( 38 eyes ) . Group I patients were given prophylactic intravitreal injection of vancomycin 1 mg and ceftazidime 2.25 mg at the conclusion of primary repair . Group II patients were not given prophylactic intravitreal antibiotics . All the patients received intravenous ciprofloxacin . RESULTS The incidence of endophthalmitis was higher in group II ( 7 of 38 eyes ; 18.42 % ) compared to group I ( 2 of 32 eyes ; 6.25 % ) . Both the patients who developed endophthalmitis despite prophylactic intravitreal antibiotics in group I had an initially undetected intraocular foreign body ( eyelash ) in the vitreous cavity . CONCLUSIONS Prophylactic intravitreal broad spectrum antibiotic injection decreases the risk of post-traumatic endophthalmitis OBJECTIVE To evaluate the efficacy of intraocular gentamicin sulfate and clindamycin in the prevention of acute posttraumatic bacterial endophthalmitis following penetrating eye injuries . METHOD We conducted a multicenter , r and omized , double-masked controlled trial of 346 eyes with penetrating eye injury . Following primary repair , eyes were r and omized to intracameral or intravitreal injection of 40 microg of gentamicin sulfate and 45 microg of clindamycin ( cases ) vs balanced salt solution ( controls ) . MAIN OUTCOME MEASURE Occurrence of endophthalmitis within 2 weeks . RESULTS Endophthalmitis occurred in 8 ( 2.3 % ) of 167 eyes in the control group and only in 1 ( 0.3 % ) of 179 eyes in the case group ( P = .04 ; odds ratio , 8.93 [ 95 % confidence interval , 1.11 - 71.43 ] ) . In eyes with an intraocular foreign body , endophthalmitis developed in 7 of 25 control eyes and in none of 27 eyes receiving antibiotics . However , in eyes without an intraocular foreign body , endophthalmitis developed in 1 of 142 eyes and 1 of 152 eyes in the 2 groups , respectively ( P value for interaction = .04 ) . Intravitreal injection was superior to intracameral injection in preventing endophthalmitis ( P value for interaction = .01 ) . Vitreous culture results were positive in 6 ( 67 % ) of 9 eyes with endophthalmitis . CONCLUSION Intraocular gentamicin and clindamycin are effective in the prevention of acute posttraumatic bacterial endophthalmitis in eyes with retained intraocular foreign body . APPLICATION TO CLINICAL PRACTICE Prophylaxis of traumatic endophthalmitis . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00398658 PURPOSE To assess the clinical effect of pars plana vitrectomy ( PPV ) with intravitreous antibiotic drugs or silicone oil endotamponade in post-traumatic endophthalmitis on eyes without detachment of the retina . METHODS Thirty cases of eyes with penetrating injury associated with endophthalmitis without retina detachment had been treated with PPV plus intravitreous antibiotic drugs or silicone oil tamponade . All the patients in the study received intravenous , subconjunctival and topical medications antibiotics . RESULTS All the patients were followed up for 3 to 12 months . Postoperative intraocular infection of 30 eyes ( 30 patients ) were controlled . The best-corrected visual acuity was significantly improved in both groups postoperatively ( P < 0.05 ) . The rate of postoperative retinal detachment in the PPV combined with intravitreal antibiotics group was 21.1 % ( 4/19 ) vs. 9 % (1/11)in the PPV combined with silicone oil There was no significant difference in postoperative endotamponade group . There was no significant difference in postoperative complications between two groups . CONCLUSIONS PPV combined with silicone oil tamponade may have beneficial effect on the surgical treatment of traumatic bacterial endophthalmitis associated without retinal detachment , but the surgery may be used in some cases which have bad retinal condition or uncontrollable inflammation PURPOSE We studied events leading to the development of posttraumatic endophthalmitis by examining the significance of 15 factors on microbial contamination of injured eyes . METHODS A prospect i ve study was done of 30 ruptured globes in patients admitted to an urban medical center . Cultures were taken from the conjunctiva before and after preoperative disinfection and from the anterior chamber at the beginning and end of wound repair . Twenty-five of 30 patients received a three-day regimen of intravenous antibiotics that were begun before surgery . RESULTS Anterior chamber sample s grew microorganisms in ten ( 33 % ) of 30 eyes , with positive cultures recovered from specimens taken at the beginning of wound repair in eight eyes and at the end of wound repair in six eyes . Contamination with indigenous flora may have occurred at the time of injury in one eye and during repair in another eye . Microbes recovered included Staphylococcus , Corynebacterium , and Aspergillus species . No patient developed endophthalmitis . Of the 15 factors studied , only intravenous antibiotics significantly decreased the incidence of positive anterior chamber cultures in eyes treated before wound repair compared with eyes not receiving such therapy ( P = .002 ) . CONCLUSIONS Despite the frequency of anterior chamber microbial contamination during injury or repair of the wound , with our treatment protocol and the presence of physiologic mechanisms to reduce intraocular microbes , no eyes developed clinical endophthalmitis . With our limited sample size only intravenous antibiotic therapy was found significantly to reduce anterior chamber microorganisms at the time of surgical repair , supporting their prophylactic use against the development of posttraumatic endophthalmitis PURPOSE To evaluate the outcomes of pars plana vitrectomy and silicone oil injection for the treatment of infectious endophthalmitis . METHODS 35 cases of endophthalmitis secondary to phacoemulsification ( 20 patients ) , trabeculectomy ( 8 patients ) , perforating trauma ( 2 patients ) , trauma ( 2 patients ) , corneal transplantation ( 1 patient ) , vitrectomy ( 1 patient ) and corneal ulceration ( 1 patient ) were retrospectively studied . Patients were separated into two groups : Group 1 ( n=24 ) : intravitreal antibiotic injection , associated with topical and oral antibiotics ; Group 2 ( n=11 ) : vitrectomy with intravitreal antibiotic injection and silicone oil injection . The follow-up ranged from 1 to 48 months ( mean of 16 months ) . RESULTS From 24 patients in group 1 , 11 patients ( 45.83 % ) , had infection controlled with intravitreal antibiotic injection only ; 13 patients ( 54.15 % ) regressed to uncontrolled endophthalmitis , in which two patients ( 8.33 % ) were su bmi tted to evisceration and one patient ( 4.16 % ) had corneal melting . The remaining 10 patients ( 41.66 % ) with uncontrolled endophthalmitis were su bmi tted to pars plana vitrectomy and silicone oil injection . Six patients ( 25 % ) from Group I had retinal detachment during the first month of follow-up and also required pars plana vitrectomy and silicone oil injection . In Group 2 patients ( n=11 ) , all of them had controlled infection at the first procedure . In one case ( 9.09 % ) , a severe proliferative vitreoretinopathy induced loss of vision . CONCLUSION These results suggest that silicone oil tamponade might be beneficial in the treatment strategy of infectious endophthalmitis Purpose : To compare the use of systemic oral and intravenous antibiotics as a prophylactic measure to prevent endophthalmitis in patients with open globe injuries . Methods : This prospect i ve study was conducted on 1,255 consecutive patients with open globe injuries due to sharp or blunt trauma in a hospital setting in Tehran , Iran from January , 2011 to May , 2013 . The patients were r and omly divided into two groups and either received intravenous or oral systemic antibiotics as a measure to prevent endophthalmitis . The patients who developed endophthalmitis were followed for 1 year . Results : In the first group , 12 patients ( 1.8 % ) developed endophthalmitis until postoperative Day 3 and 2 more patients ( 0.3 % ) developed endophthalmitis until the end of Week 1 . These numbers in group receiving oral antibiotics were 8 ( 1.3 % ) , 5 ( 0.8 % ) , and 13 patients , respectively , showing no statistically significant difference between the 2 groups . There was also no statistically significant difference in the visual acuity of patients developing endophthalmitis in these 2 groups 1 year postoperatively . Conclusion : No statistically significant difference in the occurrence of postoperative endophthalmitis or the visual acuity 1 year after operation among patients with open globe injuries receiving intravenous or oral systemic antibiotics as a prophylactic measure was observed AIM Post-traumatic endophthalmitis is one of the most severe complications occurring in 2 - 17 % after open globe injuries . Early intravenous antibiotics may minimise the risk of post-traumatic endophthalmitis . The design of a new study to evaluate the role of an additional intravitreal antibiotic injection in the prevention of post-traumatic endophthalmitis is presented in this paper . PATIENTS AND METHODS A prospect i ve , multicentre , r and omised controlled study was design ed . Patients with penetrating or perforating eye injuries will be included up to the year 2010 . The wound closure and IOFB ( intraocular foreign body ) removal must be performed within 24 hours after the trauma . After grouping into low risk ( e. g. , metallic IOFB ) or high risk patients ( e. g. , agricultural trauma , organic IOFB ) each patient will be r and omised for 1 ) intravenous moxifloxacin only or 2 ) intravenous moxifloxacin plus intravitreal 1 mg Vancomycin plus 2.25 mg [ DOSAGE ERROR CORRECTED ] Ceftazidim . RESULTS 17 European Departments of Ophthalmology have agreed to participate . The rate of post-traumatic endophthalmitis in each group will be statistically compared . The follow-up period of this study will last 6 months . CONCLUSION Other Departments of Ophthalmology are invited to join the TEPT |
13,808 | 28,382,668 | RESULTS Overall , PA interventions commonly found positive effects on academic behavior , with few exceptions .
There were additional unique findings regarding differences in outcome measures and PA treatments .
CONCLUSIONS The findings from these studies are significant and support the implementation or continuation of PA in schools to improve academic behavior and associated performance . | BACKGROUND In this systematic review , we assessed the existing research describing the effects of physical activity ( PA ) on academic behavior , with a special focus on the effectiveness of the treatments applied , study design s , outcome measures , and results . | The appropriateness of recess in the elementary program continues to be question ed although generally it is believed to be useful by elementary principals despite a dearth of supportive data . This study was a developmental study of the effects of physical activity on concentration . Comparison of passive and directed physical education activities on the concentration of second- , third- , and fourth- grade children was made . The Woodcock-Johnson Test of Concentration showed better performance by the fourth grade rs and within Grade 4 in favor of the physical activity group . A structured physical activity or a classroom activity immediately prior to a concentration task was not detrimental to children in Grade s 2 and 3 . Fourth- grade children performed significantly better on a test of concentration after engaging in a physical activity Teachers complain about growing concentration deficits and reduced attention in adolescents . Exercise has been shown to positively affect cognitive performance . Due to the neuronal connection between the cerebellum and the frontal cortex , we hypothesized that cognitive performance might be influenced by bilateral coordinative exercise ( CE ) and that its effect on cognition might be already visible after short bouts of exercise . One hundred and fifteen healthy adolescents aged 13 - 16 years of an elite performance school were r and omly assigned to an experimental and a control group and tested using the d2-test , a test of attention and concentration . Both groups performed the d2-test after a regular school lesson ( pre-test ) , after 10 min of coordinative exercise and of a normal sport lesson ( NSL , control group ) , respectively ( post-test ) . Exercise was controlled for heart rate ( HR ) . CE and NSL enhanced the d2-test performance from pre- to post-test significantly . ANOVA revealed a significant group ( CE , NSL ) by performance interaction in the d2-test indicating a higher improvement of CE as compared to NSL . HR was not significantly different between the groups . CE was more effective in completing the concentration and attention task . With the HR being the same in both groups we assume that the coordinative character of the exercise might be responsible for the significant differences . CE might lead to a pre-activation of parts of the brain which are also responsible for mediating functions like attention . Thus , our results support the request for more acute CE in schools , even in elite performance schools PURPOSE This study evaluated the effects of a classroom-based physical activity program on children 's in-school physical activity levels and on-task behavior during academic instruction . METHODS Physical activity of 243 students was assessed during school hours . Intervention-group students ( N = 135 ) received a classroom-based program ( i.e. , Energizers ) . The control group ( N = 108 ) did not receive Energizers . On-task behavior during academic instruction time was observed for 62 third- grade ( N = 37 ) and fourth- grade students ( N = 25 ) before and after Energizers activities . An independent groups t-test compared in-school physical activity levels between intervention and control classes . A multiple-baseline across-classrooms design was used to evaluate the effectiveness of the Energizers on on-task behavior . Additionally , a two-way ( time [ pre- vs postobservation ] x period [ baseline vs intervention ] ) repeated- measures analysis of variance compared on-task behavior between observation periods . Magnitudes of mean differences were evaluated with Cohen 's delta ( ES ) . RESULTS Students in the intervention group took significantly ( P < 0.05 ) more in-school steps ( 5587 + /- 1633 ) than control-group students ( 4805 + /- 1543 ) , and the size of this difference was moderate ( ES = 0.49 ) . The intervention was effective in improving on-task behavior ; after the Energizers were systematic ally implemented , on-task behavior systematic ally improved . The improvement in on-task behavior of 8 % between the pre-Energizers and post-Energizers observations was statistically significant ( P < 0.017 ) , and the difference was moderate ( ES = 0.60 ) . Likewise , the least on-task students improved on-task behavior by 20 % after Energizers activities . This improvement was statistically significant ( P < 0.001 ) and meaningful ( ES = 2.20 ) . CONCLUSION A classroom-based physical activity program was effective for increasing daily in-school physical activity and improving on-task behavior during academic instruction BACKGROUND This study examined associations of fitness and fatness with cognitive processes , academic achievement , and behavior , independent of demographic factors , at the baseline of an exercise trial . METHODS Overweight , sedentary but otherwise healthy 7 - 11 year olds ( N=170 ) participated in a study of health , cognition and achievement in the Augusta , GA area from 2003 - 2006 . Children underwent evaluations of fatness and fitness , psychological assessment s of cognition and academic achievement , and behavior ratings by parents and teachers . Partial correlations examined associations of fitness and fatness with cognitive and achievement scores and behavior ratings , controlling for demographic factors . RESULTS Fitness was associated with better cognition , achievement and behavior , and fatness with worse scores . Specifically , executive function , mathematics and reading achievement , and parent ratings of child behavior were related to fitness and fatness . Teacher ratings were related to fitness . CONCLUSION These results extend prior studies by providing reliable , st and ardized measures of cognitive processes , achievement , and behavior in relation to detailed measures of fitness and fatness . However , cross-sectional associations do not necessarily indicate that improving one factor , such as fatness or fitness , will result in improvements in factors that were associated with it . Thus , r and omized clinical trials are necessary to determine the effects of interventions This study tested the effect of a structured aerobic exercise program on anger expression in healthy overweight children . Overweight sedentary children were r and omly assigned to an aerobic exercise program or a no-exercise control condition . All children completed the Pediatric Anger Expression Scale at baseline and posttest . Anger Out and Anger Expression scores were lower for the exercise condition at posttest . Fitness improvements contributed significantly to final models , and points earned for adherence correlated negatively with posttest Anger Out . An aerobic exercise program might be an effective strategy to reduce anger expression , including reduction of aggressive behavior , in overweight children NEW FINDINGS What is the central question of this study ? Children are spending more than 60 % of their waking day sedentary . The consequences of excessive sedentary behaviour are not well understood in the child , but there is growing evidence that with increasing sedentary time , cardiovascular risk in childhood also increases . What is the main finding and its importance ? Our findings show that a 3 h period of uninterrupted sitting causes a profound ( 33 % ) reduction in vascular function in young girls . Importantly , we also demonstrate that breaking up sitting with regular exercise breaks can prevent this . Excessive sedentary behaviour has serious clinical and public health implication s ; however , the physiological changes that accompany prolonged sitting in the child are not completely understood . Herein , we examined the acute effect a prolonged period of sitting has upon superficial femoral artery function in 7- to 10-year-old girls and the impact of interrupting prolonged sitting with exercise breaks . Superficial femoral artery endothelium-dependent flow-mediated dilatation , total shear rate , antero grade and retro grade shear rates and oscillatory shear index were assessed before and after two experimental conditions : a 3 h uninterrupted period of sitting ( SIT ) and a 3 h period of sitting interrupted each hour with 10 min of moderate-intensity exercise ( EX ) . A mixed-model analysis of variance was used to compare between-condition and within-condition main effects , controlling for the within-subject nature of the experiment by including r and om effects for participant . Superficial femoral artery endothelium-dependent flow-mediated dilatation decreased significantly from pre- to post-SIT ( mean difference 2.2 % flow-mediated dilatation ; 95 % confidence interval = 0.60 - 2.94 % , P < 0.001 ) . This relative decline of 33 % was abolished in the EX intervention . Shear rates were not significantly different within conditions . Our data demonstrate the effectiveness of short but regular exercise breaks in off setting the detrimental effects of uninterrupted sitting in young girls |
13,809 | 27,387,328 | Longitudinal research supported the cross-sectional analyses . | Adolescent girls have been targeted as a priority group for promoting physical activity levels however it is unclear how this can be achieved .
There is some evidence to suggest that social support could impact the physical activity levels of adolescent girls , although the relationship is complex and not well understood .
We aim ed to systematic ally review and meta-analyse the relationship between social support and physical activity in adolescent girls , exploring how different types and providers of social support might influence the relationship . | Background This study aim ed to evaluate the associations of selected demographic , individual , social , and environmental factors with moderate-to-vigorous physical activity ( MVPA ) in a sample of children and adolescents . Methods MVPA was assessed among youth ( n = 294 ) 10 - 17-years-old using the ActiGraph accelerometer . Youth completed measures of demographic and individual variables related to physical activity ( PA ) , perceived social support by parents and peers , and perceived neighborhood characteristics . Parents completed the long-form of the International Physical Activity Question naire . The Physical Activity and Media Inventory was used to measure the home environment and Geographical Information Systems software was used to measure the physical neighborhood environment . Bivariate correlations and hierarchical multiple regression were conducted stratified by gender . Results Boys participated in significantly more MVPA than girls . In hierarchical analyses , peer support , home PA equipment , and temperature were significantly associated with MVPA among boys whereas distance to the school they attended was associated with MVPA among girls . The final models accounted for 25 % and 15 % of the variance in MVPA among boys and girls , respectively . Conclusions Important differences exist among the individual , social , and environmental factors related to MVPA between boys and girls . Boys ' levels of activity appear to be influenced by factors closely linked to unstructured and social types of activities whereas girls ' activities relate to internal and external barriers as well as their proximity to their schools . The prospect i ve contribution of these important individual , social , and environmental factors to changes in MVPA among children and adolescents remains to be determined PURPOSE The objectives of this study were to describe longitudinal trends in adolescent physical activity in a sample of U.S. adolescents and to assess the effect of multiple individual , parental , and environmental factors on initial level and rates of change in adolescent physical activity . METHODS Study subjects were 12,812 boys and girls 10 to 18 years of age who were participating in the Growing Up Today Study and their mothers . We used accelerated longitudinal analysis to describe trajectories of physical activity from 1997 - 1999 , and r and om effects linear mixed models to determine which factors were independently associated with baseline physical activity and changes in physical activity over time . RESULTS Mean hours of physical activity ranged from 7.3 - 11.6 hours per week in boys and from 8.0 - 11.2 hours per week in girls . Physical activity was best modeled as a quadratic function of age , increasing until early adolescence and declining after age 13 in boys and girls . Multivariable modeling demonstrated that variables associated with physical activity level at baseline in boys and girls were age , body mass index , psychosocial variables , personal attitudes about body shape , perceived peer attitudes about body shape/fitness , parental attitudes about physical activity , parental physical activity , and environmental barriers to physical activity . Age was the only factor that predicted change in physical activity over time . CONCLUSIONS Interventions to increase physical activity in adolescents should begin before adolescence . Interventions may be more effective if they are multimodal and focus on modifiable individual , parental , and environmental factors OBJECTIVE To test whether self-efficacy for overcoming barriers to physical activity has direct , indirect ( i.e. , mediated ) , or moderating relations with naturally occurring change in perceived social support and declines in physical activity during high school . METHODS Latent growth modeling was used with measures completed in the 8th , 9th , and 12th grade s by a cohort of 195 Black and White girls . RESULTS Self-efficacy was stable and moderated the relation between changes in physical activity and perceived social support . Girls who maintained a perception of strong social support had less of a decline in physical activity if they also had high self-efficacy . However , girls having high self-efficacy had a greater decline in physical activity if they perceived declines in social support . CONCLUSIONS R and omized controlled trials of physical activity interventions based on social cognitive theory should consider that the influence of girls ' perceptions of social support on their physical activity may differ according to their efficacy beliefs about barriers to physical activity Background Few studies have examined the mediators of behavior change in successful school-based physical activity interventions . The aim of this study was to explore potential mediators of physical activity in the Fit-4-Fun program for primary school children . Design Group r and omized controlled trial . Methods Four primary schools were recruited in April , 2011 and r and omized by school into intervention or control conditions . Participants included 213 children ( mean age = 10.7 years ± 0.6 ; 52.2 % female ) with the treatment group ( n = 118 ) completing the 8-week multi-component Fit-4-Fun program . Participants were assessed at baseline , 3- and 6-months . Physical activity was measured using Yamax SW700 pedometers ( mean steps/day ) and question naires were used to assess constructs from Social Cognitive Theory and Competence Motivation Theory . Hypothesized mediators measured included social support from peers , parents and teachers ; physical activity self-efficacy ( barrier and task ) ; enjoyment ; and perceived school physical environment . Mediation was assessed using Preacher and Hayes ’ multiple mediation regression SPSS macro . Action theory ( A ) , conceptual theory ( B ) and the significance of the product of coefficients ( AB ) are reported . Results The intervention had a significant effect on physical activity ( p<0.001 ) . The action theory test results revealed significant treatment effects at 3-months for perceived school environment ( A=0.28 , p<0.001 ) ; and at 6-month follow-up for perceived school environment ( A=0.058 , p<0.001 ) , teacher social support ( A=0.54 , p<0.05 ) and enjoyment ( A=-0.23 , p<0.05 ) . The conceptual theory test revealed a significant relationship between changes in teacher social support and changes in physical activity at 6-month follow-up ( B=828 , P<0.05 ) . Teacher social support was shown to have a significant mediating effect on physical activity ( AB = 445 , CI = 77 - 1068 steps , proportion= 13 % ) , and perceived school environment approached significance ( AB = 434 , CI= -415 to 1507 steps , proportion= 13 % ) . Conclusions The Fit-4-Fun program successfully targeted social support for physical activity provided by classroom teachers which contributed to improved physical activity in children . These results demonstrate that classroom teachers play a key role in influencing physical activity behavior outcomes in children . Trial Registration No : Aims : Habits of leisure time sports activity , similar to other health behaviours , are established during late childhood and early adolescence . While regular leisure time sports activity is a natural part of children 's lifestyle , it starts to decrease during adolescence , particularly among girls . Among the factors influencing children 's sports activity , the role of parents , peers , and other members of children 's social networks seem to be crucial . The purpose of this study was to determine the role of social influences in early adolescents ' leisure time sports activity and to examine gender differences . Methods : Data were collected from middle school students using r and omly selected classes from four schools in distinct school districts in Szeged , Hungary , using a self-administered question naire ( n = 548 ) in which a response rate of 91 % was achieved . Respondents were 10—15 years of age ( mean = 12.2 years , SD = 1.2 years ) with 54.9 % of the sample male and 45.1 % female . Results : Results show significant others as an important influence on sport-related behaviours and suggest that during early adolescence girls ' sports participation is particularly influenced by the social influence of peers ( e.g. friends , classmates , boy/girlfriend ) . Conclusions : Our findings suggest that health promotion programmes should build on possible social influences , i.e. the role of peers , parents and significant others in general , in fostering adolescents ' physical activity |
13,810 | 26,953,891 | Molecular methods can also improve monitoring of regional changes in the serotypes and identification frequency of S. pneumoniae and H. influenzae over time or after vaccine implementation , such as after introduction of the 7-valent pneumococcal conjugate vaccine .
Globally , S. pneumoniae and H. influenzae remain the predominant otopathogens associated with OM as identified through bacterial culture ; however , molecular methods continue to improve the frequency and accuracy of detection of individual serotypes . | BACKGROUND Otitis media ( OM ) is amongst the most common childhood diseases and is associated with multiple microbial pathogens within the middle ear .
Global and temporal monitoring of predominant bacterial pathogens is important to inform new treatment strategies , vaccine development and to monitor the impact of vaccine implementation to improve progress toward global OM prevention . | OBJECTIVE To determine the bacteriologic efficacy of ceftriaxone in nonresponsive acute otitis media in children . METHODS In a prospect i ve study 92 patients ages 3 to 36 months ( median , 11 months ) with culture-proved nonresponsive acute otitis media were studied from January , 1995 , through August , 1997 . The patients were treated with intramuscular ceftriaxone ( 50 mg/kg/l/day ) for 3 days . Middle ear fluid was aspirated for culture by tympanocentesis on day of enrollment ( Day 1 ) ; a second tap was performed on Days 4 to 10 . Additional middle ear fluid cultures were obtained if clinical relapse occurred . Bacteriologic failure was defined by positive culture on Days 4 to 10 . Patients were followed until Day 17+/-2 . Susceptibility was measured by E test . RESULTS The main drugs administered before enrollment were amoxicillin ( 38 % ) , amoxicillinclavulanate ( 25 % ) and cefaclor ( 20 % ) . Organisms recovered ( n=105 ) were : Haemophilus influenzae , 54 ; Streptococcus pneumoniae , 47 ; Moraxella catarrhalis , 2 ; and Streptococcus pyogenes , 2 . Thirty-four ( 72 % ) of the 47 S. pneumoniae isolates were intermediately resistant to penicillin ( MIC 0.1 to 1.0 microg/ml ) , but all were susceptible to ceftriaxone ( MIC < 0.5 microg/ml ) . Bacteriologic eradication was achieved in 100 of 105 ( 95 % ) cases : 54 of 54 ( 10O% ) H. influenzae , 43 of 47 ( 92 % ) S. pneumoniae , 1 of 2 ( 50 % ) M. catarrhalis and 2 of 2 ( 100 % ) S. pyogenes . Bacteriologic success ( with no relapse ) occurred in 13 of 13 ( 100 % ) penicillin-susceptible S. pneumoniae vs. 28 of 34 ( 82 % ) S. pneumoniae intermediately resistant to penicillin ( 4 cases of bacteriologic failure and 2 cases of relapse ) . CONCLUSION A 3-day intramuscular ceftriaxone regimen is efficacious for the treatment of nonresponsive acute otitis media . The optimal duration of treatment in cases of nonresponsive acute otitis media and whether ceftriaxone is efficacious for the treatment of nonresponsive otitis media caused by S. pneumoniae highly resistant to penicillin is yet to be determined Background The immunogenicity , reactogenicity , and safety of the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine ( PHiD-CV ) co-administered with routine childhood vaccines were evaluated among infants from Singapore and Malaysia , where PHiD-CV has been licensed . Methods In the primary vaccination phase , 298 infants from Singapore and 168 infants from Malaysia were r and omised to receive the Phase III Clinical ( Clin ) or the Commercial ( Com ) lot of PHiD-CV at 2 , 3 , and 5 months of age . In the booster vaccination phase , 238 toddlers from Singapore received one dose of the PHiD-CV Commercial lot at 18–21 months of age . Immune responses to pneumococcal polysaccharides were measured using 22F-inhibition enzyme-linked immunosorbent assay ( ELISA ) and functional opsonophagocytic activity ( OPA ) assay and to protein D , using ELISA . Results Immune responses induced by primary vaccination with the PHiD-CV Commercial lot were non-inferior to the Phase III Clinical lot in terms of adjusted antibody geometric mean concentration ( GMC ) ratios for each vaccine pneumococcal serotype and protein D. For each vaccine pneumococcal serotype , ≥93.6 % and ≥88.5 % of infants from Malaysia and Singapore had post- primary vaccination antibody concentrations ≥0.2 μg/mL and OPA titres ≥8 , in the Clin and Com groups , respectively . For each vaccine pneumococcal serotype , ≥60.8 % and ≥98.2 % of toddlers from Singapore had pre- and post-booster antibody concentrations ≥0.2 μg/mL , in the Clin and Com groups , respectively . All children , except one , had measurable anti-protein D antibodies and the primary and booster doses of the co-administered vaccines were immunogenic . The incidence of each grade 3 solicited symptom was ≤11.1 % in both study phases . No serious adverse events considered causally related to vaccination were reported throughout the study . Conclusions PHiD-CV given as three-dose primary vaccination to infants in Singapore and Malaysia and booster vaccination to toddlers in Singapore was shown to be immunogenic with a clinical ly acceptable-safety profile . This study has been registered at http://www . clinical trials.govNCT00808444 and NCT01119625 Objective : To describe NP and AOM otopathogens during the time frame 2007 to 2009 , 6 to 8 years after the introduction of 7-valent pneumococcal conjugate ( PCV7 ) in the United States and to compare nasopharyngeal ( NP ) colonization and acute otitis media ( AOM ) microbiology in children 6 to 36 months of age having first and second AOM episodes with children who are otitis prone . Methods : Prospect ively , the microbiology of NP colonization and AOM episodes was determined in 120 children with absent or infrequent AOM episodes . NP sample s were collected at 7 routine visits between 6 and 30 months of age and at the time of AOM . For first and subsequent AOM episodes , middle ear fluid ( MEF ) was obtained by tympanocentesis . Eighty otitis prone children were comparatively studied . All 200 children received age-appropriate doses of PCV7 . Results : We found PCV7 serotypes were virtually absent : ( 0.9 % isolated from both NP and MEF ) in both study groups . However , non-PCV7 serotypes replaced PCV serotypes such that the frequency of isolation of S. pneumoniae ( Spn ) was nearly equal to that of non-typeable Haemophilus influenzae ( NTHi ) . M. catarrhalis ( Mcat ) was less common and Staphylococcus aureus infrequent in the NP and MEF from the 2 groups . The proportion of Spn , NTHi and Mcat causing AOM was similar in children with first and second AOM episodes compared to otitis prone children . However , oxacillin-resistant Spn isolated from the NP and MEF was 19 % for the absent/infrequent and 58 % for the otitis prone groups , P < 0.0001 . Beta-lactamase producing NTHi occurred more frequently in the otitis prone group , P = 0.04 . Conclusions : Six to 8 years after widespread use of PCV7 , Spn strains expressing vaccine-type serotypes have virtually disappeared from the NP and MEF of vaccinated children . NP colonization and AOM has changed to non-PCV7 strains of Spn . NTHi continues to be a major AOM pathogen . The otopathogens in first and second AOM and in otitis prone children are very similar although Spn and NTHi are more often antibiotic resistant in the otitis prone Background Acute Otitis Media ( AOM ) is an important and common disease of childhood . Bacteria isolated from cases of clinical ly problematic AOM in German children were identified and characterized . Methods In a prospect i ve non-interventional study in German children between 3 months and less than 60 months of age with Ear , Nose and Throat Specialist –confirmed AOM , middle ear fluid was obtained by tympanocentesis ( when clinical ly indicated ) or by careful sampling of otorrhea through/at an existing perforation . Results In 100 children with severe AOM , Haemophilus influenzae was identified in 21 % ( 18/21 , 85.7 % were non-typeable [ NTHi ] ) , Streptococcus pneumoniae in 10 % , S. pyogenes in 13 % and Moraxella catarrhalis in 1 % . H. influenzae was the most frequently identified pathogen in children from 12 months of age . H. influenzae and S. pneumoniae were equally prevalent in children aged 3–11 months , but S. pyogenes was most frequently isolated in this age group . NTHi AOM disease appeared prevalent in all ages . Conclusions NTHi , S. pneumoniae and S. pyogenes are implicated as important causes of complicated AOM in children in Germany . NTHi disease appears prevalent in all ages . The impact of vaccination to prevent NTHi and S. pneumoniae AOM may be substantial in this population and is worth investigating The safety and immunogenicity of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine ( PHiD-CV , Synflorix ™ ) were assessed in 240 healthy Chilean children r and omized to receive 3 doses of PHiD-CV ( PHiD-CV group ) or hepatitis A vaccine ( HAV control group ) at 2 - 4 - 6 months of age . All were offered 1 HAV dose at 12 months ( outside study ) . The PHiD-CV group received a second HAV dose at 18 - 21 months and PHiD-CV booster at 20 - 23 months . The HAV control group received 2 PHiD-CV catch-up doses at 18 - 21 and 20 - 23 months . Adverse events were recorded and pneumococcal antibody responses and opsonophagocytic activity ( OPA ) were measured . Both PHiD-CV vaccination schedules were well tolerated and immunogenic against the pneumococcal vaccine serotypes and protein D. The reactogenicity of PHiD-CV primary , booster and catch-up doses was in line with previous PHiD-CV studies , although generally higher than with HAV . For each vaccine serotype , the percentage of subjects with antibody concentrations ≥0.2 µg/ml ( GSK 's 22F-inhibition ELISA ) was at least 93.2 % following 3 PHiD-CV primary doses and at least 97.4 % post-booster ; percentages with OPA titers ≥8 were at least 91.7 % post-booster . After 2-dose catch-up , at least 94.3 % of children had antibody concentrations ≥0.2 µg/ml against each serotype except 6B ( 84.3 % ) ; at least 95.2 % had OPA titers ≥8 except against serotypes 1 , 5 and 6B . In conclusion , the safety profiles of 2 PHiD-CV vaccination schedules ( 3-dose primary plus booster and 2-dose catch-up ) were in line with previous studies and PHiD-CV was immunogenic for all 10 vaccine serotypes and protein BACKGROUND Clinical symptoms and signs in acute otitis media ( AOM ) may differ depending on the various pneumococcal serotypes causing the disease . Alteration in clinical presentation of AOM could be expected after wide-scale pneumococcal vaccinations if there were considerable differences between vaccine serotypes and nonvaccine serotypes . METHODS In this study , data from 831 children in the control arm of the Finnish Otitis Media Vaccine Trial were used . The children were followed up prospect ively in 8 study clinics from 2 to 24 months of age . If AOM was diagnosed , myringotomy was done , and middle ear fluid was aspirated for bacterial culture . Clinical symptoms and signs of AOM were routinely recorded on structured case report forms . RESULTS Consistent with previous studies , 60 % of pneumococcal episodes were caused by vaccine serotypes . There were no major differences between the clinical presentations of AOM due to different serotypes or serotype categories . However , earache was more often associated with AOM caused by vaccine and cross-reactive serotypes , compared with AOM caused by non-vaccine-related serotypes ( 42 % vs. 29 % ; odds ratio , 1.66 ; 95 % confidence interval , 1.02 - 2.70 ) . CONCLUSIONS Introduction of the currently available pneumococcal conjugate vaccine is unlikely to result in a remarkable alteration in the clinical presentation of pneumococcal AOM in infants BACKGROUND Because of the increasing number of resistant middle ear pathogens reported from different centers worldwide , an active surveillance of the microbiology and susceptibility pattern of middle ear pathogens is required for proper antimicrobial recommendations among different regions of the world . OBJECTIVE To study the microbiology and susceptibility pattern of middle ear pathogens obtained from Costa Rican children with acute otitis media . METHODS Between 1992 and 1997 a diagnostic tympanocentesis was performed in 398 Costa Rican patients with acute otitis media . Middle ear fluid was obtained for culture and minimal inhibitory concentrations were determined by the E-test technique in those isolates obtained between October , 1995 , and January , 1997 . RESULTS The most common pathogens cultured were Streptococcus pneumoniae ( 30 % ) , Haemophilus influenzae ( 14 % ) , Staphylococcus aureus ( 4 % ) and Streptococcus pyogenes ( 4 % ) . Moraxella catarrhalis was uncommon . Beta-lactamase production was low ( 3.7 % ) among the H. influenzae isolates but frequent among the Staphylococcus aureus ( 57.1 % ) and M. catarrhalis ( 100 % ) strains . Overall 9 of 46 S. pneumoniae isolates ( 19.6 % ) exhibited decreased susceptibility to penicillin of which 8 isolates ( 17.4 % ) showed intermediate and one strain ( 2.2 % ) high level resistance . Among the penicillin-susceptible S. pneumoniae isolates , susceptibility to the following antimicrobials was : 81 % , azithromycin ; 89 % , clarithromycin ; and 100 % , ceftriaxone and trimethoprim-sulfamethoxazole ( TMP-SMX ) . Among the penicillin-resistant S. pneumoniae isolates the percentage of susceptible strains was 89 % for azithromycin , clarithromycin and ceftriaxone and 67 % for TMP-SMX . CONCLUSIONS Based on this microbiologic information the agents considered first line drugs in the treatment of acute otitis media in Costa Rica remain amoxicillin or TMP-SMX Abstract Objectives Otitis media ( OM ) is one of the most frequent diseases of childhood , with a minority of children suffering from recurrent acute otitis media ( rAOM ) or chronic otitis media with effusion ( COME ) , both of which are associated with significant morbidity . We investigated whether the microbiological profiling could be used to differentiate between these two conditions . Methods Children up to five years of age , with rAOM ( n = 45 ) or COME ( n = 129 ) and scheduled for tympanostomy tube insertion were enrolled in a prospect i ve study between 2008 and 2009 . Middle ear fluids ( n = 119 ) and nasopharyngeal sample s ( n = 173 ) were collected during surgery for bacterial culture and PCR analysis to identify Streptococcus pneumoniae , Haemophilus influenzae and Moraxella catarrhalis , and to detect 15 distinct respiratory viruses . Results The occurrence of bacterial and viral pathogens in middle ear fluids did not significantly differ between patients suffering from rAOM and COME . In both patient cohorts , H. influenzae and rhinovirus were the predominant pathogens in the middle ear and nasopharynx . Nasopharyngeal carriage with two or three bacterial pathogens was associated with the presence of bacteria in middle ear fluid ( P = 0.04 ) . The great majority of the bacteria isolated from middle ear fluid were genetically identical to nasopharyngeal isolates from the same patient . Conclusions Based on these results , we propose that the common perception that rAOM is associated with recurrent episodes of microbiologically mediated AOM , whereas COME is generally a sterile inflammation , should be reconsidered Background : Recent review s have highlighted the unpredictability of immunologic interference when multivalent conjugated vaccines are coadministered with other pediatric vaccines . Objective : To evaluate immunogenicity , safety , and reactogenicity of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine ( PHiD-CV ; Synflorix , GlaxoSmithKline Biologicals ) and DTPa-IPV-Hib ( Pediacel , Sanofi Pasteur MSD ) when coadministered as a 3-dose primary vaccination course . Material and Methods : In a single-blind , single-center , r and omized controlled trial in the Netherl and s , healthy infants ( n = 780 ) were r and omly assigned ( 1:1:1 ) to receive either ( 1 ) PHiD-CV + DTPa-HBV-IPV/Hib ( Infanrix Hexa , GlaxoSmithKline Biologicals ) , ( 2 ) PHiD-CV + DTPa-IPV-Hib , or ( 3 ) 7-valent pneumococcal conjugate vaccine ( Prevenar/Prevnar , Pfizer Inc. ) + DTPa-IPV-Hib at 2 , 3 , and 4 months of age . Blood sample s were collected 1 month after dose 3 . Diary cards were used to record safety and reactogenicity . Results : Antibody concentrations elicited by PHiD-CV coadministered with DTPa-IPV-Hib were noninferior to those following DTPa-HBV-IPV/Hib coadministration for 9 of 10 vaccines pneumococcal serotypes and protein D. For serotype 18C ( conjugated to tetanus toxoid ) , the antibody concentration was higher with DTPa-HBV-IPV/Hib coadministration ( 1.73 vs. 1.07 & mgr;g/mL ) . The percentages of infants with antibody concentrations ≥0.2 & mgr;g/mL ( 68.9%–100 % in the PHiD-CV + DTPa-HBV-IPV/Hib group vs. 64.9%–100 % in the PHiD-CV + DTPa-IPV-Hib group ) and with measurable opsonophagocytic activity ( 56.1%–100 % in the PHiD-CV + DTPa-HBV-IPV/Hib group vs. 61.1%–100 % in the PHiD-CV + DTPa-IPV-Hib group ) were comparable for all serotypes in both PHiD-CV groups . Group differences in antibody responses to the DTPa-IPV-Hib antigens remained within the predefined limit for noninferiority . Safety and reactogenicity profiles were comparable across groups . Conclusions : PHiD-CV and DTPa-IPV-Hib were immunogenic and well tolerated when coadministered as a 3-dose primary vaccination course A multicentre open-label , r and omised trial was performed to compare the efficacy and safety of cefpodoxime proxetil bd and cefaclor tds in the treatment of acute otitis media in children . A total of 167 children aged from 1 month to 11 years were enrolled in five centres : 78 treated with cefpodoxime and 83 treated with cefaclor , were evaluated in the ITT analysis . After tympanocentesis and culture of middle ear fluid , a pathogen was isolated from 85 ( 53 % ) of the 161 evaluable patients for the ITT analysis . The organisms isolated were as follows : Streptococcus pneumoniae : ( n = 33 , 37.5 % ) ; Haemophilus influenzae : ( n = 22 , 25 % ) ; Staphylococcus aureus : ( n = 15 , 17.1 % ) ; Streptococcus pyogenes : ( n = 8 , 9.1 % ) ; Moraxella catarrhalis : ( n = 2 , 2.3 % ) ; others ( n = 6 , 6.8 % ) . Success ( defined as a satisfactory clinical outcome , either cure or improvement ) was achieved at the end of treatment , in 93.6 % of ther patients in the cefpodoxime group and 91.6 % of the patients in the cefaclor group ( P > 0.05 ) . Clinical recurrence was identified at the follow-up visit ( 30 days after inclusion ) , in 6.4 % of the cefpodoxime-treated patients and 7.2 % of the cefaclor-treated patients ( P > 0.05 ) . The drugs were well tolerated by 78/79 ( 99 % ) of patients in the cefpodoxime-treated group and 80/85 ( 94 % ) in the cefaclor-treated group . The incidence of adverse effects was higher in the cefaclor group than in the cefpodoxime group , but this was not statistically significant ( P > 0.05 ) . IN conclusion , cefpodaxime proxetil administered bd is as effective as cefaclor administered tds in the treatment of acute otitis media in children . The less frequent dosing schedule of cefpodoxime ( bd ) compared with cefaclor ( tds ) appears to be more convenient for the treatment of the infections in children Background Because previous studies have indicated that otitis media may be a polymicrobial disease , we prospect ively analyzed middle ear effusions of children undergoing tympanostomy tube placement with multiplex polymerase chain reaction for four otopathogens . Methods Middle ear effusions from 207 children undergoing routine tympanostomy tube placement were collected and were classified by the surgeon as acute otitis media ( AOM ) for purulent effusions and as otitis media with effusion ( OME ) for non-purulent effusions . DNA was isolated from these sample s and analyzed with multiplex polymerase chain reaction for Haemophilus influenzae , Streptococcus pneumoniae , Alloiococcus otitidis , and Moraxella catarrhalis . Results 119 ( 57 % ) of 207 patients were PCR positive for at least one of these four organisms . 36 ( 30 % ) of the positive sample s indicated the presence of more than one bacterial species . Patient sample s were further separated into 2 groups based on clinical presentation at the time of surgery . Sample s were categorized as acute otitis media ( AOM ) if pus was observed behind the tympanic membrane . If no pus was present , sample s were categorized as otitis media with effusion ( OME ) . Bacteria were identified in most of the children with AOM ( 87 % ) and half the children with OME ( 51 % , p < 0.001 ) . A single bacterial organism was detected in middle ear effusions from children with AOM more often than those with OME ( 74 % versus 33 % , p < 0.001 ) . Haemophilus influenzae was the predominant single organism and caused 58 % of all AOM in this study . Alloiococcus otitidis and Moraxella catarrhalis were more frequently identified in middle ear effusions than Streptococcus pneumoniae . Conclusions Haemophilus influenzae , Streptococcus pneumoniae , Alloiococcus otitidis , and Moraxella catarrhalis were identified in the middle ear effusions of some patients with otitis media . Overall , we found AOM is predominantly a single organism infection and most commonly from Haemophilus influenzae . In contrast , OME infections had a more equal distribution of single organisms , polymicrobial entities , and non-bacterial agents Background : Primary vaccination with the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine ( PHiD-CV ) was previously shown to be immunogenic and well tolerated in Malian children . Data on booster vaccination with a fourth consecutive dose of PHiD-CV are available for Europe , Asia and Latin America but are lacking for Africa . The present study evaluated further the safety , reactogenicity and immunogenicity of a fourth consecutive ( booster ) dose of PHiD-CV . Results : Low incidences of AEs with grade 3 intensity ( 2.1 % of subjects ) were observed . There were no reports of large swelling reactions and serious adverse events . One month post-booster vaccination , for each vaccine pneumococcal serotype , at least 97.8 % of subjects had antibody concentrations ≥ 0.2 μg/ml , and at least 97.1 % of subjects had opsonophagocytic activity ≥ 8 . From pre- to post-booster , a 12.3-fold increase in anti-protein D geometric mean concentration was observed . Methods : This phase III , open-label study was conducted in Ouelessebougou , Mali , between November 2009 and June 2010 . The study population consisted of Malian children previously primed ( 3 doses ) with PHiD-CV in study NCT00678301 receiving a fourth consecutive ( booster ) dose of PHiD-CV in the second year of life . The incidences of adverse events ( AEs ) with grade 3 intensity ( primary objective ) or of any intensity ( secondary objective ) , and the immunogenicity ( secondary objective ) of the PHiD-CV booster dose were assessed . Conclusion : A booster dose of PHiD-CV was well tolerated when administered to Malian children in the second year of life and was highly immunogenic for all 10 vaccine pneumococcal serotypes and NTHi protein D. ( Clinical Trials.gov identifier : NCT00985465 Background Acute otitis media ( AOM ) is one of the most frequently encountered bacterial infections in children aged < 5 years ; Streptococcus pneumoniae ( S. pneumoniae ) and non-typeable Haemophilus influenzae ( NTHi ) are historically identified as primary AOM causes . Nevertheless , recent data on bacterial pathogens causing AOM in Latin America are limited . This prospect i ve study aim ed to identify and characterize bacterial etiology and serotypes of AOM cases including antimicrobial susceptibility in < 5 year old Colombian children . Methods From February 2008 to January 2009 , children ≥3 months and < 5 years of age presenting with AOM and for whom a middle ear fluid ( MEF ) sample was available were enrolled in two medical centers in Cali , Colombia . MEF sample s were collected either by tympanocentesis procedure or spontaneous otorrhea swab sampling . Bacteria were identified using st and ard laboratory methods , and antimicrobial resistance testing was performed based on the 2009 Clinical and Laboratory St and ards Institute ( CLSI ) criteria . Most of the cases included in the study were sporadic in nature . Results Of the 106 enrolled children , 99 were included in the analysis . Bacteria were cultured from 62/99 ( 63 % ) of sample s with S. pneumoniae , H. influenzae , or S. pyogenes . The most commonly isolated bacteria were H. influenzae in 31/99 ( 31 % ) and S. pneumoniae in 30/99 ( 30 % ) of sample s. The majority of H. influenzae episodes were NTHi ( 27/31 ; 87 % ) . 19F was the most frequently isolated pneumococcal serotype ( 10/30 ; 33 % ) . Of the 30 S. pneumoniae positive sample s , 8/30 ( 27 % ) were resistant to tetracycline , 5/30 ( 17 % ) to erythromycin and 8/30 ( 27 % ) had intermediate resistance to penicillin . All H. influenzae isolates tested were negative to beta-lactamase . Conclusions NTHi and S. pneumoniae are the leading causes of AOM in Colombian children . A pneumococcal conjugate vaccine that prevents both pathogens could be useful in maximizing protection against AOM Background The high cost of pneumococcal conjugate vaccine ( PCV ) and local epidemiological factors contributed to evaluating different PCV dosing-schedules . This study evaluated the immunogenicity of seven-valent PCV ( PCV7 ) administered at 6-weeks ; 14-weeks and 9-months of age . Methods 250 healthy , HIV-unexposed infants were immunized with PCV7 concurrently with other childhood vaccines . Serotype-specific anti-capsular IgG concentrations were measured one-month following the 1st and 2nd PCV-doses , prior to and two-weeks following the 3rd dose . Opsonophagocytic killing assay ( OPA ) was measured for three serotypes following the 2nd and 3rd PCV7-doses . Immunogenicity of the current schedule was compared to a historical cohort of infants who received PCV7 at 6 , 10 and 14 weeks of age . Results The proportion of infants with serotype-specific antibody ≥0.35 µg/ml following the 2nd PCV7-dose ranged from 84 % for 6B to ≥89 % for other serotypes . Robust antibody responses were observed following the 3rd dose . The proportion of children with OPA ≥8 for serotypes 9V , 19F and 23F increased significantly following the 3rd PCV7-dose to 93.6 % ; 86.0 % and 89.7 % respectively . The quantitative antibody concentrations following the 2nd PCV7-dose were comparable to that after the 3rd -dose in the 6 - 10 - 14 week schedule . Geometric mean concentrations ( GMCs ) following the 3rd PCV7-dose were higher for all serotypes in this study compared to the historical cohort . Conclusions The studied PCV7 dosing schedule induced good immune responses , including higher GMCs following the 3rd-dose at 9-months compared to when given at 14-weeks of age . This may confer longer persistence of antibodies and duration of protection against pneumococcal disease Background : This r and omized single-blind study in Korea evaluated noninferiority of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine ( PHiD-CV ) versus the 7-valent pneumococcal conjugate vaccine ( 7vCRM ) when both were coadministered with H. influenzae type b ( Hib ) conjugate vaccine , as opposed to coadministration with diphtheria-tetanus-acellular pertussis-based combination vaccines in previous studies . Methods : Infants received 3 primary doses at 2 , 4 , and 6 months and a booster dose at 12 to 18 months of PHiD-CV ( N = 374 ) or 7vCRM ( N = 129 ) , both coadministered with Hib vaccine . Immune responses were measured 1 month postdose 3 and postbooster using 22F-inhibition enzyme-linked immunosorbent assay and functional opsonophagocytic activity assay . Results : PHiD-CV-induced antibody responses against each of the vaccine pneumococcal serotypes and protein D. Noninferiority to 7vCRM was demonstrated for all 10 PHiD-CV serotypes in terms of percentages of subjects reaching an antibody concentration ≥0.2 & mgr;g/mL after primary vaccination . Post primary and postbooster , percentages of subjects with antibody concentration ≥0.2 & mgr;g/mL or opsonophagocytic activity titer ≥8 were generally consistent between groups for each pneumococcal serotype common to both vaccines . The safety and reactogenicity profiles of PHiD-CV and 7vCRM were generally comparable after both primary and booster vaccination . Conclusions : In this Korean study , 3-dose PHiD-CV priming followed by a booster dose was immunogenic for all 10 vaccine pneumococcal serotypes and protein D. Noninferiority to 7vCRM in terms of enzyme-linked immunosorbent assay threshold responses postpriming was demonstrated . The safety and reactogenicity profiles of both vaccines when coadministered with Hib vaccine were generally comparable Background : The otopathogen distribution colonizing the nasopharynx ( NP ) and causing acute otitis media ( AOM ) is in flux following the introduction of pneumococcal conjugate vaccine 7 ( PCV7 ) and will continue to change . Methods : Two hundred seventy-seven children were followed prospect ively ; tympanocentesis was performed during AOM and 208 NP sample s were collected to compare with middle ear fluid ( MEF ) isolates . Eight hundred sixty-three NP sample s were collected at 7 healthy visits between 6 and 30 months of age . All children received PCV7 until April 2010 when it was substituted by PCV13 . Multilocus sequence typing was used to speciate Streptococcus pneumoniae . Results : The distribution of otopathogens in the MEF during the study time frame was stable . PCV7 serotypes of pneumococci were virtually absent . The frequency of isolation of S. pneumoniae was 26–36 % compared with 28–34 % for nontypeable Haemophilus influenzae . Moraxella catarrhalis isolation was less common , 7–18 % . The proportion of S. pneumoniae that were penicillin nonsusceptible was stable during the 3 years , 40–52 % . All M. catarrhalis and 34 % of nontypeable H. influenzae were & bgr;-lactamase producing . NP isolates of otopathogens at onset of AOM included the isolate from the MEF and was dissimilar from the distribution at times of health . Sequence types 320 and 199 of S. pneumoniae expressing serotypes 19A and 15 most often caused AOM . Conclusions : The otopathogen distribution , antibiotic susceptibility and the diversity of strains within the S. pneumoniae species during 2008 through late 2010 were stable . NP isolation of otopathogens at onset of AOM better reflected , albeit incompletely , likely MEF isolates compared with NP isolates at times of health Background . Gatifloxacin is an 8-methoxyfluoroquinolone with good activity against respiratory pathogens . Objectives . To document the bacteriologic and clinical efficacy of gatifloxacin in recurrent/nonresponsive acute otitis media ( AOM ) . Methods . One hundred sixty patients 6 to 48 months of age with recurrent/nonresponsive AOM received gatifloxacin suspension ( 10 mg/kg once daily for 10 days ) . Recurrent AOM was defined as ≥3 AOM episodes during the previous 6 months or ≥4 AOM episodes during the previous 12 months . Nonresponsive AOM was defined as AOM occurring ≤14 days after completing antibiotic treatment or not improving after ≥48 h of therapy . Middle ear fluid ( MEF ) obtained by tympanocentesis pretreatment ( Day 1 ) and 3 to 5 days after initiation of treatment ( Days 4 to 6 ) was cultured . Additional MEF cultures were obtained if clinical failure or recurrence of AOM occurred . Bacteriologic failure was defined by culture-positive MEF during treatment . Patients were followed until Days 22 to 28 . Susceptibility was determined by broth microdilution . Results . One hundred twenty-eight ( 80 % ) patients completed treatment , and 32 discontinued the study prematurely ( adverse events , 17 ; lost to follow-up , 10 ; consent withdrawal , 3 ; and laboratory abnormalities , 2 ) . From 89 patients ( median age , 1 year ; median number of prior AOM episodes , 4 ; range , 0 to 12 ) , 121 pathogens were recovered : Haemophilus influenzae , 74 ( 61 % ) ; Streptococcus pneumoniae , 36 ( 30 % ) ; Moraxella catarrhalis , 9 ( 7 % ) ; and Streptococcus pyogenes , 2 ( 2 % ) . The 36 S. pneumoniae isolates were susceptible to gatifloxacin ( MIC50 0.25 & mgr;g/ml ) ; 26 of 36 ( 72 % ) were penicillin-nonsusceptible ( 15 fully resistant ) . All 74 H. influenzae isolates were susceptible to gatifloxacin ( MIC ≤ 0.03 mg/ml ) . Fourteen of 74 ( 19 % ) and 9 of 9 ( 100 % ) H. influenzae and M. catarrhalis isolates , respectively , produced beta-lactamase . Bacteriologic eradication was achieved for 118 of 121 ( 98 % ) pathogens : 74 of 74 H. influenzae ; 34 of 36 ( 94 % ) S. pneumoniae ; 9 of 9 M. catarrhalis ; and 1 of 2 S. pyogenes . Clinical improvement/cure at end of treatment was seen in 103 of 114 ( 90 % ) clinical ly evaluable patients . Clinical recurrence of AOM after completion of therapy occurred in 31 patients . Of the 27 recurrent AOM cases in which tympanocentesis was performed , there were 16 ( 59 % ) new infections , 4 ( 15 % ) culture-negative results and only 7 ( 26 % ) true bacteriologic relapses . Adverse events were recorded in 21 of 160 ( 13 % ) patients : vomiting , 16 ; diarrhea , 3 ; maculopapular rash , 2 . No articular adverse events were recorded . Conclusion . Gatifloxacin is efficacious and safe for the treatment of recurrent/nonresponsive AOM BACKGROUND Acute otitis media ( AOM ) is a main cause for antimicrobial prescription in Latin America . Pathogen diversity in different geographic regions underscores the need for up date d knowledge on AOM microbiology . AIM To prospect ively determine the role of bacteria and viruses in Chilean children with AOM . METHODS Between July , 1998 , and June , 1999 , children > 3 months with a presumptive diagnosis of AOM were referred to the study ear , nose and throat physician . Middle ear fluid and nasopharyngeal aspirates were obtained from children with confirmed AOM and processed for common bacteria , Mycoplasma pneumoniae , Chlamydia pneumoniae and viruses . Antimicrobial susceptibility patterns and serotypes of Streptococcus pneumoniae strains were determined . RESULTS An ear , nose and throat physician confirmed diagnoses for 222 ( 42 % ) of 529 children referred with diagnosis of AOM , and 170 children met eligibility criteria for the study . One or more pathogens were detected in 140 of 170 ( 82 % ) children . Predominant bacteria were S. pneumoniae ( 37 % ) , Haemophilus influenzae ( 24 % ) and Streptococcus pyogenes ( 13 % ) . M. catarrhalis was detected in 2 children , C. pneumoniae was found in 1 and M. pneumoniae was not detected . Viruses were detected in 22 children ( 13 % ) from nasopharyngeal aspirates , and in 6 of them the same virus was detected in middle ear fluid . Penicillin-resistant ( intermediate and high ) S. pneumoniae represented 40 % of isolates and 10 % of H. influenzae were beta-lactamase producers . All 10 penicillin-resistant S. pneumoniae strains were resistant to cefuroxime . Eighteen S. pneumoniae serotypes were detected and 19F was associated with high level penicillin resistance . CONCLUSION This study can impact local management of AOM , and it should encourage continuous surveillance of AOM microbiology in Chile and other developing countries In acute otitis media ( AOM ) , a means of prediction of the bacterial pathogen based on symptoms and signs would be valuable in selecting appropriate antimicrobial treatment . Children in the control arm ( n=831 ) in the Finnish Otitis Media Vaccine Trial were prospect ively observed in a study clinic setting from the age of 2 to 24 months . In patients with AOM , myringotomy with aspiration was performed , and middle ear fluid sample s were cultured for bacterial pathogens . Symptoms and signs of respiratory infections were thoroughly recorded . Streptococcus pneumoniae , Moraxella catarrhalis , and Haemophilus influenzae were the most common bacterial pathogens . Pneumococcal AOM was associated with more-severe AOM characterized by fever and earache . AOM due to H. influenzae was associated with eye symptoms and findings . Accurate prediction of a bacterial cause of infection based on symptoms and signs of AOM was not possible , but a specific cause was predicted in some situations , with a high probability of applicability to clinical practice Background : The heptavalent pneumococcal conjugate vaccine ( PCV7 ) has a considerable effect on the epidemiology of pneumococcal disease . The aim of this observational hospital-based study was to examine the effect of the PCV7 ( introduced in our setting s in 2004 ) on the epidemiology of spontaneously draining acute otitis media . Methods : Results of all middle ear fluid cultures ( n = 3446 ) obtained from children with acute otitis media complicated with otorrhea before the introduction of immunization ( between 2000 and 2003 ) were compared with those ( n = 2134 ) obtained during a similar post-PCV7 period ( between 2005 and 2008 ) . Results of cultures obtained between 2006 and 2008 were examined prospect ively , whereas those obtained in previous years were retrospectively review ed . Results : Following PCV7 immunization , the rates of otorrhea visits per 10,000 emergency department visits decreased by 38 % from 133 to 83 ( 95 % confidence interval of the difference , 42–53 ; P < 0.001 ) , mainly as a result of the decrease in the incidence of pneumococcal disease ( 48 % decrease—25 vs. 13 per 10,000 emergency department visits ; P < 0.001 ) . Otorrhea due to Haemophilus influenzae decreased by 20 % ( 20–16 per 10,000 visits ; P < 0.001 ) . Serotype 19A accounted for 1 of 47 ( 2 % ) pneumococcal strains in 2006 , for 5 of 34 ( 15 % ) in 2007 , and for 13 of 53 ( 25 % ) in 2008 ( P for trend : 0.001 ) . In the postvaccine years , penicillin-resistant pneumococcal strains ( minimum inhibitory concentration ≥2 & mgr;g/mL ) increased from 4 % to 13 % ( P < 0.001 ) . However , the proportion of pneumococci resistant to macrolides decreased ( 44 % vs. 35 % ; P = 0.01 ) . Conclusions : After the introduction of immunization , otorrhea incidents decreased considerably , mainly because of the decrease in pneumococcal disease . H. influenzae is now the predominant organism . Serotype 19A has increased significantly and is the most common nonvaccine pneumococcal serotype . Penicillin resistance has increased in recent years The present study was performed to eluci date the clinical outcome , and etiology of acute otitis media ( AOM ) in children based on virologic and bacteriologic tests . The study group consisted of 120 children aged 6 to 144 months with AOM . Middle ear fluid ( MEF ) was tested for viral pathogens by reverse transcriptase polymerase chain reaction ( RT-PCR ) and for bacteria by gram-staining and culture . Clinical response was assessed on day 2 to 4 , 11 to 13 , 26 to 28 . Respiratory viruses were isolated in 39 patients ( 32.5 % ) . Respiratory syncytial virus ( RSV ) ( 46.5 % ) was the most common virus identified in MEF sample s , followed by human rhinovirus ( HRV ) ( 25.6 % ) , human coronavirus ( HCV ) ( 11.6 % ) , influenza ( IV ) type A ( 9.3 % ) , adenovirus type sub type A ( AV ) ( 4 % ) , and parainfluenza ( PIV ) type -3 ( 2 % ) by RT-PCR . In total 69 bacterial species were isolated from 65 ( 54.8 % ) of 120 patients . Streptococcus pneumoniae ( S. pneumoniae ) was the most frequently isolated bacteria . Viral RNA was detected in 31 ( 56.3 % ) of 55 bacteria-negative specimens and in 8 ( 12.3 % ) of 65 bacteria-positive MEF sample s. No significant differences were found between children representing viral infection alone , combined viral and bacterial infection , bacterial infection alone , and neither viral nor bacterial infection , regarding clinical cure , relapse and reinfection rates . A significantly higher rate of secretory otitis media ( SOM ) was observed in alone or combined RSV infection with S. pneumonia or Haemophilus influenzae ( H. influenzae ) than in other viruses infection . Conclusion . This study provides information about etiologic agents and diagnosis of AOM in Turkish children . The findings highlight the importance of common respiratory viruses and bacterial pathogens , particularly RSV , HRV , S. pneumoniae and H. influenzae , in predisposing to and causing AOM in children CONTEXT Concern has been raised about the possible emergence of a bacterial strain that is untreatable by US Food and Drug Administration ( FDA ) -approved antibiotics and that causes acute otitis media ( AOM ) in children . OBJECTIVE To monitor continuing shifts in the strains of Streptococcus pneumoniae that cause AOM , with particular attention to capsular serotypes and antibiotic susceptibility , following the introduction of a pneumococcal 7-valent conjugate vaccine ( PCV7 ) . DESIGN , SETTING , AND PATIENTS Prospect i ve cohort study using tympanocentesis to identify S pneumoniae strains that caused AOM in children receiving PCV7 between September 2003 and June 2006 . All children were from a Rochester , New York , pediatric practice . MAIN OUTCOME MEASURE Determination of serotypes and antibiotic susceptibility of S pneumoniae causing AOM . RESULTS Among 1816 children in whom AOM was diagnosed , tympanocentesis was performed in 212 , yielding 59 cases of S pneumoniae infection . One strain of S pneumoniae belonging to serotype 19A was a new genotype and was resistant to all antibiotics approved by the FDA for use in children with AOM . This strain was identified in 9 cases ( 2 in 2003 - 2004 , 2 in 2004 - 2005 , and 5 in 2005 - 2006 ) . Four children infected with this strain had been unsuccessfully treated with 2 or more antibiotics , including high-dose amoxicillin or amoxicillin-clavulanate and 3 injections of ceftriaxone ; 3 had recurrent AOM ; and for 2 others , the infection was their first in life . The first 4 cases required tympanostomy tube insertion after additional unsuccessful antibiotic therapies . Levofloxacin was used in the subsequent 5 cases , with resolution of infection without surgery . CONCLUSION In the years following introduction of PCV7 , a strain of S pneumoniae has emerged in the United States as an otopathogen that is resistant to all FDA -approved antibiotics for treatment of AOM in children Objectives . To compare the bacteriologic and clinical efficacy of amoxicillin/clavulanate and azithromycin in patients with acute otitis media ( AOM ) , particularly the ability to eradicate the predominant AOM pathogens from middle ear fluid as assessed by m and atory second tympanocentesis . Methods . In this single blind study 238 infants and children with AOM were r and omized to receive amoxicillin/clavulanate ( 45/6.4 mg/kg/day in two divided doses for 10 days ) or azithromycin ( 10 mg/kg on Day 1 , then 5 mg/kg daily on Days 2 through 5 ) . Tympanocentesis was performed before the first dose and repeated on Day 4 , 5 or 6 . Clinical response was assessed at end of therapy between Days 12 and 14 and at follow‐up between Days 22 and 28 . Results . Amoxicillin/clavulanate was significantly more likely to eradicate all bacterial pathogens [ 83 % ( 54 of 65 ) vs. 49 % ( 35 of 71 ) , P = 0.001 ] and Haemophilus influenzae [ 87 % ( 26 of 30 ) vs. 39 % ( 13 of 33 ) , P = 0.0001 ] from middle ear fluid than was azithromycin . Amoxicillin/clavulanate was also more likely to eradicate Streptococcus pneumoniae , but the difference was not statistically significant [ 90 % ( 18 of 20 ) vs. 68 % ( 3 of 19 ) , P = 0.095 ] . On Days 12 to 14 , signs and symptoms were more likely to resolve completely or improve in all culture‐positive patients [ 86 % ( 60 of 70 ) vs. 70 % ( 51 of 73 ) , P = 0.023 ] and in those with H. influenzae infections [ 91 % ( 30 of 33 ) vs. 65 % ( 22 of 34 ) , P = 0.010 ] who received amoxicillin/clavulanate compared with those who received azithromycin . Otherwise there were no significant differences between groups in clinical outcomes on Days 12 to 14 or at follow‐up . Conclusions . Our findings indicate that amoxicillin/clavulanate has superior bacteriologic and clinical efficacy compared with azithromycin in children with AOM BACKGROUND The 7-valent conjugated vaccine ( PCV7 ) was introduced into the Israeli National Immunization Program ( NIP ) in July 2009 ( 2 , 4 , 12 months schedule ; 2 dose catch-up in second year of life ) . Nationwide active prospect i ve surveillance on invasive pneumococcal disease ( IPD ) has been conducted in children since 1989 . In the current study , IPD epidemiology in children < 5 years during the 20 years before and 18 months after PCV7 NIP initiation , is reported . METHODS All 27 centers performing blood/cerebrospinal fluid ( CSF ) cultures in children reported monthly IPD cases . Capture-recapture approach was used for completeness . RESULTS During 1989 - 2010 , 6022 IPD cases were reported in children < 5 years ; PCV7 serotypes ( 7VST ) caused ∼50 % of all episodes . In 2009 and 2010 , 7VST IPD incidences < 5 years of age ( per 100,000 ) were 15.9 and 5.4 , respectively ( a 43 % and 81 % decrease , respectively ) compared to 2003 - 2007 ( mean incidence 27.8 ) . Serotype 6A dynamics resembled those of 7VST . The respective overall IPD incidence decreases were 23 % and 42 % . The incidence dynamics of serotypes 1 , 3 , 5 , 7F and 19A IPD were characterized by considerable fluctuations over the study period without any upwards or downwards trend in any of the age groups . The overall incidence of serotypes not included in the 13-valent pneumococcal conjugate vaccine ( PCV13 ) did not vary significantly during the study period . By the end of 2010 , 72 % of the remaining IPD was caused by pneumococcal serotypes included in PCV13 . CONCLUSIONS An active prospect i ve long-term surveillance , showed a rapid and sharp decline in IPD in children < 5 years following initiation of NIP with PCV7 . No serotype replacement has been observed so far . The transition from PCV7 to PCV13 initiated in October 2010 may lead to a further substantial decrease in IPD . Follow-up is needed to better determine the long-term PCV effects BACKGROUND Acute otitis media ( AOM ) is a common childhood infection that is frequently treated by antibiotics . There are no prospect i ve and comprehensive trials evaluating childhood AOM for etiologic pathogens and resistance pattern in Turkey . The aims of the study were to determine the bacterial etiologies and resistance patterns , and identify the efficacy and the relapse rates of 3 days of azitromycin and 10 days of cefaclor therapy in AOM . METHODS This prospect i ve , r and omized , single-blind , open study was carried out in 78 cases of AOM . Mean age was 30.7+/-27 months . Tympanocentesis and aspiration of middle ear fluid ( MEF ) were used to obtain purulent material from the middle ear . Group 1 consisted of the cases ( n=41 ) on azitromycin therapy and Group 2 ( n=37 ) on cefaclor . Dosage of azitromycin was 10 mg/kg per day for 3 days and cefaclor 40 mg/kg per day for 10 days . The patients were evaluated on days 3 - 5 ( second visit ) , day 10 ( third visit ) , and day 30 ( fourth visit ) during follow-up . RESULTS A total of 50 species were isolated from 44 of 78 cases from which material s were obtained ( 44/78 ; 56.4 % ) . Most frequently isolated microorganism was Streptococcus pneumoniae ( n=18 ; 36 % ) , followed by Haemophilus influenzae ( n=11 ; 22 % ) , S. aureus ( n=9 ; 18 % ) , Moraxella catarrhalis ( n=4 ; 8 % ) , and group A beta-hemolytic streptococcus ( GAS , n=4 ; 8 % ) . Enterococcus faecalis was isolated from three cases and H. parainfluenzae from one . Penicillin and amoxicillin resistances of bacteria were found to be 40 and 36 % , respectively . The frequency of penicillin and amoxicillin resistance in < /=24-month age group was 59 and 66.6 % , respectively . The patients did not demonstrate significant differences in terms of cure rate on the third to fifth day ( Group 1 : 32.5 % ; Group 2 : 36.4 % ) , 10th day ( Group 1 : 76.9 % ; Group 2 : 84.8 % ) , and on 30th day ( Group 1 : 91.3 % ; Group 2 : 81.8 % ) . There were no significant differences with respect to side effects , relapse , and re-infection rate between the two groups . CONCLUSION In more than half of the AOM cases , bacteria were isolated from MEF and most frequently isolated organisms were S. pneumoniae , H. influenzae , and S. aureus . Three-day azitromycin therapy was as effective as 10-day cefaclor therapy Background : Before 7-valent pneumococcal conjugate vaccine ( PCV7 ) implementation in France , several studies had described the microbiology of acute otitis media ( AOM ) treatment failures . The causative pathogens were Streptococcus pneumoniae ( Sp ) followed by nontypable Haemophilus influenzae ( NTHi ) . The aim of this study was to describe the epidemiology of pathogens involved in AOM treatment failures or recurrences . Methods : This French multicentric prospect i ve study enrolled 143 children with AOM treatment failure between 2007 and 2009 observed by 8 ear , nose , and throat specialists . Failure was defined as the persistence of AOM symptoms after at least 48 hours of antibiotic therapy or their recurrence within 4 days after the end of treatment . St and ardized history and physical examination findings were recorded , and culture of middle ear fluid ( MEF ) was obtained . Results : Mean age was 16.9 ± 9.9 months ( median , 13.7 ) . Eighty-eight percent of children had received more than 1 dose of PCV7 , and 70.6 % attended day care . The most common antibiotic used at the time of treatment failure or recurrence was a combination of amoxicillin and clavulanate ( 51.1 % ) . Bacteriologic sampling demonstrated that in 35 % of cases ( n=50 ) , no otopathogen was cultured at the time of treatment failure or recurrence . Similar proportions of Sp and NTHi were observed in the 86 patients ( 60.1 % ) from whom only a single species was recovered from MEF ( 46.5 % for Sp , n=40 and 45.3 % for NTHi , n=39 ) . Among Sp strains , 4.4 % were penicillin susceptible , 77.8 % were penicillin intermediate , and 17.8 % were fully penicillin resistant , and serotype 19A represented 84.5 % of all serotypes detected . Among NTHi isolates , 15.5 % ( n=7 ) were & bgr;-lactamase – producing strains ( including 2 strains with only this mechanism of resistance ) , and strains with reduced susceptibility by changes in protein binding to penicillin ( & bgr;-lactamase – negative ampicillin resistant strains ) represented 35.5 % of cases . Among the 50 sterile MEF sample s , polymerase chain reaction was performed in 32 , of which 4 were positive for HI , 3 for Sp , and 3 for both . Conclusions : Among children with AOM treatment failures in France , Sp and NTHi were equally distributed ; 19A was the main Sp serotype , and the main resistance mechanism for NTHi was & bgr;-lactamase – negative ampicillin resistance Objectives : To analyze the peripheral leukocyte counts of children with acute otitis media ( AOM ) in relation to etiology , age , clinical symptoms and signs , prior antibiotic treatment , previous AOM history and pathogen eradication during antibiotic therapy . Patients and Methods : Leukocyte counts were determined at diagnosis and on days 4 to 6 of therapy in patients age 3 to 36 months with AOM enrolled in double tympanocentesis studies . Clinical status was determined by a clinical score evaluating severity of fever , irritability and tympanic membrane redness and bulging . Results : Of 771 enrolled patients , culture-positive middle ear fluid was reported in 590 ( 77 % ) : 294 ( 50 % ) Haemophilus influenzae ; 150 ( 25 % ) Streptococcus pneumoniae ; 127 ( 21 % ) H. influenzae and S. pneumoniae together ; 9 ( 2 % ) Moraxella catarrhalis ; and 10 ( 2 % ) others . Mean leukocyte count ± sd in patients with AOM caused by S. pneumoniae ( 15.7 ± 6.7 cells × 103/mm3 ) was significantly higher than those of patients with AOM caused by H. influenzae ( 13.7 ± 5.8 cells × 103/mm3 ) and patients with culture-negative AOM ( 13.8 ± 5.6 cells × 103/mm3 ) , P < 0.01 for each comparison . Mean absolute neutrophil count ( ANC ) ± sd was higher in patients with AOM caused by S. pneumoniae ( 8.6 ± 5.1 cells × 103/mm3 ) than in patients with AOM caused by H. influenzae ( 6.5 ± 4.0 cells × 103/mm3 ) or culture-negative patients ( 6.5 ± 4.4 cells × 103/mm3 ) , P < 0.05 for each comparison . When multivariant regression analysis was used , S. pneumoniae etiology and fever ( body temperature . ≥38 ° C ) were independent factors , each significantly associated with leukocyte and ANCs . A significant correlation was found between leukocyte and ANCs and higher clinical scores in patients with pneumococcal AOM ( P = 0.01 , r = 0.21 and P < 0.01 , r = 0.27 , respectively ) . The mean leukocyte count on Days 4 to 6 was lower than on Day 1 ( 11.5 ± 4.1 compared with 14.2 ± 6.0 cells × 103/mm3 , P < 0.01 ) . When paired ( Day 1 and Days 4 to 6 ) examinations were analyzed , the leukocyte counts were lower on Days 4 to 6 irrespective of bacterial eradication or persistence . Conclusions : Significantly higher leukocyte counts and ANCs were found in pneumococcal AOM than in AOM caused by H. influenzae or in culture-negative AOM . A significant decrease in leukocyte counts was found during antibiotic therapy for AOM , regardless of etiology and bacteriologic outcome . Isolation of S. pneumoniae and fever were each significantly associated with increased peripheral leukocyte and ANCs OBJECTIVE Our main aim is to analyze the bacterial involvement in otitis media with effusion ( OME ) and its effect on antimicrobial therapy . PATIENTS AND METHOD A prospect i ve study is carried out on a total of 70 children from 1 to 12 years of age distributed in 2 groups : the first is a control group of 30 healthy children and the second group comprises 40 children with OME . The surgical sample s obtained from the middle ear were processed for bacterial analysis . RESULTS In 72.5 % of OMEs , the bacterial cultures were positive . The micro-organisms isolated were : Alloiococcus otitidis ( 48.27 % ) , followed by Haemophilus influenzae not serotype B ( 17.24 % ) , Staphylococcus aureus ( n = 2 ) , and Streptococcus pneumoniae ( n = 1 ) . CONCLUSIONS In the healthy ear , the ear cavity is sterile . In most OMEs , bacteria such as Alloiococcus otitidis are identified . Knowing which bacterium is involved is essential for the prognosis and treatment of otitis media with effusion , as the high frequency of its presentation may be linked to the aetiology and /or course of the process in many patients OBJECTIVE To prospect ively identify the bacterial aetiology and antimicrobial susceptibility of problematic ( recurrent and treatment failure ) acute otitis media in Spanish children several years after the introduction of 7-valent pneumococcal conjugate vaccine . METHODS Tympanocentesis or careful sampling of spontaneous otorrhoea was performed on children aged 3 to < 36 months with recurrent acute otitis media , acute otitis media treatment failure or unresolved acute otitis media . RESULTS 105 acute otitis media episodes ( 77 sample d by tympanocentesis , 28 otorrhoea sample s ) were evaluated : 46 recurrent , 35 treatment failures , 24 unresolved acute otitis media . 74 episodes ( 70.4 % ) had at least one bacterium identified on culture : Streptococcus pneumoniae was identified in 21 episodes , Haemophilus influenzae ( all non-typeable ) in 44 , Streptococcus pyogenes in 2 , Moraxella catarrhalis in 2 . No statistically significant difference in bacterial aetiology by episode type was detected . Non-typeable H. influenzae was the most commonly isolated pathogen in all acute otitis media types and in all age sub-groups . Forty percent of S. pneumoniae isolates were multi-drug resistant . Pneumococcal serotype 19A was the most frequently identified serotype ( 7/21 episodes ) . Multi-drug resistance was found in 56 % of 19A isolates . Of non-typeable H. influenzae isolates , 15 % were ampicillin resistant and 13 % were amoxicillin/clavulanate resistant . S. pneumoniae and non-typeable H. influenzae DNA were each detected in 57 % of sample s culture negative for these pathogens , including 12 co-infections . CONCLUSION Combining culture and polymerase chain reaction results , H. influenzae and S. pneumoniae may be implicated in 70 % and 43 % of clinical ly problematic bacterial acute otitis media episodes , respectively . The impact of new vaccines to prevent both S. pneumoniae and non-typeable H. influenzae acute otitis media may be substantial in this population and is worth investigating BACKGROUND Acute otitis media ( AOM ) is one of the most common acute bacterial infection in childhood and also the most frequent reason for outpatient antibiotic therapy . Little recent information about susceptibility patterns of AOM bacterial pathogens in Turkish children has been reported . OBJECTIVE To determine the bacterial etiology of acute otitis media in children and to compare the efficiency of 3 days course of azithromycin with a 10 days course of amoxicillin-clavulanate . METHODS This prospect i ve , single blind , r and omised comparative study was carried out in 180 children with AOM . Paracentesis was performed for middle ear fluid culture before the first dose antibiotic therapy . Children with acute otitis media were r and omised to receive either low dose amoxicillin-clavulanate ( 45/6.4 mg/kg/day in two divided doses for 10 days ) or low dose azithromycin ( 10mg/kg/day for 3 days ) . Clinical response was assessed on days 2 - 4 , 11 - 13 , 26 - 28 . RESULTS Bacterial pathogens were isolated from 108 ( 60 % ) of 180 children . Streptococcus pneumoniae was the most common isolated pathogen ( 39.7 % ) , followed by Haemophilus influenzae ( 20.7 % ) , Moraxella catarrhalis ( 15.5 % ) , Staphylococcus aureus ( 13.8 % ) , Group A beta-hemolytic streptococcus ( 5.1 % ) , Escherichia coli ( 3.4 % ) and Enterococcus faecalis ( 1.7 % ) . This study demonstrated low resistance rates compared to studies of different countries . Although clinical response rates were better in patients treated with amoxicillin-clavulanate , this was not statistically significant [ 86.6 % ( 78 of 90 ) ] versus [ 95.2 % ( 80 of 84 ) ] . Success rates of amoxicillin-clavulanate were high for both S. pneumoniae and H. influenzae . Difference between success rates was not statistically significant ( P=0.144 and 0.352 ) . CONCLUSIONS Bacteria were isolated in 60 % of AOM cases . The clinical efficiency of amoxicillin-clavulanate was found to be equal compared to azithromycin in children with acute otitis media OBJECTIVES To determine the dynamics of serotype prevalence , potential coverage by pneumococcal conjugate vaccines ( PCV ) and antibiotic resistance patterns of Streptococcus pneumoniae causing acute otitis media ( AOM ) in children in southern Israel before PCV7 introduction in the routine immunization program in Israel . METHODS All S. pneumoniae isolates from middle ear fluid from children with AOM during 1999 - 2008 were included . Prospect ively collected demographic data on S. pneumoniae serotypes and antibiotic resistance patterns were analyzed . RESULTS A total of 14,911 tympanocenteses yielded 5281 ( 35 % ) S. pneumoniae . Proportion of S. pneumoniae-AOM did not vary significantly ( overall 35 % ; 33 % in 2007 ; 38 % in 2002 and 2003 ) . The most frequent serotypes were 19F , 14 , 23F and 19A ; in both Jewish and Bedouin children ; serotypes 6A and 19A contributed 6 % and 10 % , respectively , of all S. pneumoniae isolates . Serotypes included in PCV7 , PCV10 and PCV13 represented 60 % , 64 % , 85 % in Jewish children vs. 49 % , 55 % and 74 % , respectively , in Bedouin children ( P < 0.001 ) . Nonsusceptibility to TMP/SMX decreased significantly , in parallel with a significant increase in the nonsusceptibility to erythromycin , clindamycin and in multidrug resistant ( MDR ) isolates . No changes were recorded in the proportion of S. pneumoniae isolates with penicillin MIC ≥ 1.0 μg/ml . The proportion of penicillin- and erythromycin-nonsusceptible and of MDR serotype 6A and 19A isolates increased significantly in Bedouin children . CONCLUSIONS ( 1 ) No significant changes were recorded in the yearly proportions of serotypes 23F , 19F , 19A , 14 and 6A in both ethnic population s ; ( 2 ) Potential coverage of the 3 PCVs was higher in Jewish children than in Bedouin children ; ( 3 ) The relatively high coverage of macrolides- and multidrug-resistant S. pneumoniae by PCV13 and lack of increase in penicillin , erythromycin and multidrug nonsusceptibility among non-PCV13 isolates is encouraging Streptococcus pneumoniae and Haemophilus influenzae have been consistently reported to be the two major bacterial pathogens responsible for acute otitis media ( AOM ) , mainly from studies in the US and Europe . However , data on bacterial pathogens causing AOM in Latin America are limited . Underst and ing the relative importance of these pathogens in a specific setting , the serotype distribution , and their antibiotic susceptibility levels is important to provide local vaccine and treatment recommendations . We therefore conducted a prospect i ve , multi-center , tympanocentesis-based epidemiological study of Mexican children three months to less than five years of age . Fifty percent of episodes were in children who had received at least one dose of PCV7 . Overall , 64 % of sample s were culture positive for bacterial pathogens . H. influenzae and S. pneumoniae were the leading causes of bacterial AOM , detected in 34 % and 29 % of AOM episodes , respectively . The most commonly isolated S. pneumoniae serotypes were 19A , 19F and 23F . All H. influenzae isolates were identified as non-typeable . Seventy-four percent of S. pneumoniae were susceptible to penicillin , while 97 % were susceptible to amoxicillin/clavulanate . All H. influenzae sample s were susceptible to amoxicillin/clavulanate and cefotaxime , 95 % to cefuroxime and 75 % to ampicillin . Both S. pneumoniae and non-typable H. influenzae represent important targets for vaccination strategies to reduce AOM in Mexican children The immunogenicity and safety of the 10-valent pneumococcal conjugate vaccine , PHiD-CV , have been documented in European and Asian studies . In this open study conducted in Mexico ( NCT00489554 ) , 230 healthy infants received three doses of PHiD-CV and DTPa-HBV-IPV/Hib vaccines at 2 , 4 and 6 months of age and two doses of oral human rotavirus vaccine at 2 and 4 months . Serotype-specific pneumococcal responses and opsonophagocytic activity ( OPA ) were measured one month post-dose 3 . PHiD-CV ’s primary vaccination course was highly immunogenic against each of the 10 pneumococcal vaccine serotypes and carrier protein D. Antibody responses against pneumococcal serotypes and protein D were generally higher in Mexican infants compared with European antibody responses , and functional OPA responses were also higher or in the same range . The most frequent solicited local symptom was pain , with high but similar incidences of grade 3 pain reported at both injection sites ( up to 15 % of all doses ) . PHiD-CV was well tolerated , with no serious adverse events considered as causally related to vaccination . Most solicited symptoms were mild and there was no increase in incidence of solicited symptoms with successive vaccine doses |
13,811 | 26,730,561 | Effective interventions were most of those aim ed at improving employee physical or mental health .
Less consistent results were reported from integrated interventions targeting occupational health and safety management , injury prevention , or organizational cost savings .
Integrated approaches have been posed as comprehensive solutions to complex issues . | The study objective was to conduct a systematic review of the effectiveness of integrated workplace interventions that combine health promotion with occupational health and safety . | Objective : Workplace cancer prevention initiatives have been least successful with blue-collar workers . This study assesses whether an intervention integrating health promotion with occupational health and safety results in significant and meaningful increases in smoking cessation and consumption of fruits and vegetables , compared to a st and ard health promotion intervention , for workers overall and for blue-collar workers in particular . Methods : A r and omized controlled design was used , with 15 manufacturing worksites assigned to a health promotion ( HP ) or a health promotion plus occupational health and safety intervention ( HP/OHS ) , and compared from baseline ( 1997 ) to final ( 1999 ) . The response rates to the survey were 80 % at baseline ( n = 9019 ) and 65 % at final ( n = 7327 ) . Both groups targeted smoking and diet ; the HP/OHS condition additionally incorporated reduction of occupational exposures . Results : Smoking quit rates among blue-collar workers in the HP/OHS condition more than doubled relative to those in the HP condition ( OR = 2.13 , p = 0.04 ) , and were comparable to quit rates of white-collar workers . No statistically significant differences between groups were found for mean changes in fruits and vegetables . Conclusions : Integration of occupational health and safety and health promotion may be an essential means of enhancing the effectiveness of worksite tobacco control initiatives with blue-collar workers BACKGROUND Environmental influences on health and health behavior have an important place in research on worksite health promotion . We tested the validity and internal consistency of a new measure of organizational health and safety climate that was used in a large r and omized trial of a worksite cancer prevention program ( the Working Well Trial ) . The result ing scales then were applied to assess intervention effects . METHODS This study uses data from a subset of 40 worksites in the Working Well Trial . Employees at 20 natural gas pipeline worksite and 20 rural electrical cooperatives completed a cross-sectional question naire at baseline and 3-year follow-up . RESULTS A factor analysis of this self-report instrument produced a two-factor solution . The result ing health and safety climate scales had good internal consistency ( Cronbach 's alpha = 0.74 and 0.82 , respectively ) and concurrent validity . The health climate scale was correlated more highly with organizational measures that were indicative of a supportive health climate than those indicating supportive safety climate , while the reverse was true of the safety climate scale . Changes in health climate were associated with the number of smoking and smokeless tobacco programs offered at the worksites at the time of the 3-year follow-up ( r = 0.46 and 0.42 , respectively ) . The scales were not correlated with most employee health behaviors . The health climate scores increased at intervention worksites , compared with scores at control worksites ( F[1,36 ] = 7.57 , P = 0.009 ) . CONCLUSIONS The health and safety climate scales developed for this study provide useful instruments for measuring organizational change related to worksite health promotion activities . The Working Well Intervention result ed in a significant improvement in worksite health climate AIM This paper is the report of a pilot study to assess if an Integrated Health Programme would reduce sick leave and subjective health complaints , and increase coping in a population of nursing personnel . BACKGROUND . The work group in Norway with most sick leave is healthcare workers . More than 50 % of the sick leave is because of subjective health complaints . Work place physical exercise interventions have a documented positive effect on sick leave . METHOD After baseline screening , employees who had agreed to participate ( n=40 ) were r and omized to an intervention or control group . The intervention group participated in an Integrated Health Programme twice weekly during working hours . The programme consisted of physical exercise , stress management training , health information and an examination of the participants ' workplace . The control group was offered the same intervention after the project was finished . This study was carried out from 2001 to 2002 . FINDINGS There were no statistically significant effects on sick leave or health-related quality of life . The intervention group reported fewer neck complaints compared to the control group , but otherwise there were no effects on subjective health complaints . However , the subjective effects were large and highly statistically significant , the intervention group reporting improvement in health , physical fitness , muscle pain , stress management , maintenance of health and work situation . CONCLUSION The Integrated Health Programme was not effective in reducing sick leave and subjective health complaints , but may be of use to employers wanting to increase employee job satisfaction and well-being According to prior reports , blue-collar workers are less likely to participate in worksite health promotion programs than are white-collar workers . This study examined worker participation in the WellWorks worksite cancer prevention intervention , which integrated health promotion and health protection . Analyses were conducted to assess relationships among participation in health promotion and health protection programs , and workers ' perceptions of management changes to reduce potential occupational exposures . Results indicate that blue-collar workers were less likely to report participating in health promotion activities than white-collar workers . A significant association was observed between participation in nutrition- and exposure-related activities , suggesting that participation in programs to reduce exposures to occupational hazards might contribute to blue-collar workers ' participation in health promotion activities . Furthermore , when workers were aware of changes their employer had made to reduce exposures to occupational hazards , they were more likely to participate in both smoking control and nutrition activities , even when controlling for job category . These findings have clear implication s for future worksite cancer prevention efforts OBJECTIVES We examined the efficacy of a cancer prevention intervention design ed to improve health behaviors among working-class , multiethnic population s employed in small manufacturing businesses . METHODS Worksites were r and omly assigned to an intervention or minimal-intervention control condition . The intervention targeted fruit and vegetable consumption , red meat consumption , multivitamin use , and physical activity . RESULTS Employees in the intervention group showed greater improvements for every outcome compared with employees in the control group . Differences in improvement were statistically significant for multivitamin use and physical activity . Intervention effects were larger among workers than among managers for fruit and vegetable consumption and for physical activity . CONCLUSIONS The social- context model holds promise for reducing disparities in health behaviors . Further research is needed to improve the effectiveness of the intervention PROBLEM STATEMENT Nurses have one of the highest rates of work-related musculoskeletal injury of any profession . Over the past 30 years , efforts to reduce work-related musculoskeletal disorders in nurses have been largely unsuccessful . SPECIFIC AIMS The primary goal of this program was to create safer working environments for nursing staff who provide direct patient care . Our first objective was to design and implement a multifaceted program that successfully integrated evidence -based practice , technology , and safety improvement . The second objective was to evaluate the impact of the program on injury rate , lost and modified work days , job satisfaction , self-reported unsafe patient h and ling acts , level of support for program , staff and patient acceptance , program effectiveness , costs , and return on investment . INTERVENTION The intervention included six program elements : ( 1 ) Ergonomic Assessment Protocol , ( 2 ) Patient H and ling Assessment Criteria and Decision Algorithms , ( 3 ) Peer Leader role , " Back Injury Re source Nurses " , ( 4 ) State-of-the-art Equipment , ( 5 ) After Action Review s , and ( 6 ) No Lift Policy . METHODS A pre-/post design without a control group was used to evaluate the effectiveness of a patient care ergonomics program on 23 high risk units ( 19 nursing home care units and 4 spinal cord injury units ) in 7 facilities . Injury rates , lost work days , modified work days , job satisfaction , staff , and patient acceptance , program effectiveness , and program costs/savings were compared over two nine month periods : pre-intervention ( May 2001-January 2002 ) and post-intervention ( March 2002-November 2002 ) . Data were collected prospect ively through surveys , weekly process logs , injury logs , and cost logs . RESULTS The program elements result ed in a statistically significant decrease in the rate of musculoskeletal injuries as well as the number of modified duty days taken per injury . While the total number of lost workdays decreased by 18 % post-intervention , this difference was not statistically significant . There were statistically significant increases in two subscales of job satisfaction : professional status and tasks requirements . Self-reports by nursing staff revealed a statistically significant decrease in the number of ' unsafe ' patient h and ling practice s performed daily . Nurses ranked program elements they deemed to be " extremely effective " : equipment was rated as most effective ( 96 % ) , followed by No Lift Policy ( 68 % ) , peer leader education program ( 66 % ) , ergonomic assessment protocol ( 59 % ) , patient h and ling assessment criteria and decision algorithms ( 55 % ) , and lastly after action review s ( 41 % ) . Perceived support and interest for the program started at a high level for managers and nursing staff and remained very high throughout the program implementation . Patient acceptance was moderate when the program started but increased to very high by the end of the program . Although the ease and success of program implementation initially varied between and within the facilities , after six months there was strong evidence of support at all levels . The initial capital investment for patient h and ling equipment was recovered in approximately 3.75 years based on annual post-intervention savings of over $ 200,000/year in workers ' compensation expenses and cost savings associated with reduced lost and modified work days and worker compensation . CONCLUSIONS This multi-faceted program result ed in an overall lower injury rate , fewer modified duty days taken per injury , and significant cost savings . The program was well accepted by patients , nursing staff , and administrators . Given the significant increases in two job satisfaction subscales ( professional status and task requirements ) , it is possible that nurse recruitment and retention could be positively impacted Objective Blue-collar workers are difficult to reach and less likely to successfully quit smoking . The objective of this study was to test a training site-based smoking cessation intervention . Methods This study is a r and omized-controlled trial of a smoking cessation intervention that integrated occupational health concerns and was delivered in collaboration with unions to apprentices at 10 sites ( n = 1,213 ) . We evaluated smoking cessation at 1 and 6 months post-intervention . Results The baseline prevalence of smoking was 41 % . We observed significantly higher quit rates in the intervention versus control group ( 26 % vs. 16.8 % ; p = 0.014 ) 1 month after the intervention . However , the effects diminished over time so that the difference in quit rate was not significant at 6 month post-intervention ( 9 % vs. 7.2 % ; p = 0.48 ) . Intervention group members nevertheless reported a significant decrease in smoking intensity ( OR = 3.13 ; 95 % CI : 1.55–6.31 ) at 6 months post-intervention , compared to controls . Conclusion The study demonstrates the feasibility of delivering an intervention through union apprentice programs . Furthermore , the notably better 1-month quit rate results among intervention members and the greater decrease in smoking intensity among intervention members who continued to smoke underscore the need to develop strategies to help reduce relapse among blue-collar workers who quit smoking This study is a prospect i ve multicentre cohort study entitled Work and Health in the Processing and Engineering Industries , the AHA Study ( AHA is the Swedish abbreviation for the study ) . Four large workplaces in Sweden participated during the years from 2000 to 2003 . The present report has two objectives : ( 1 ) to present a comprehensive occupational health intervention programme and ( 2 ) to evaluate this programme with a focus on lifestyle ( smoking and exercise ) , health related quality of life ( HRQoL ) and sick leave . Interventions were provided on an individual and group level , including evidence -based methods for four health/focus areas ( individual level ) and a group intervention based on a survey-feedback methodology . The analyses in this report were exclusively employed at an organizational level . The proportion of smokers decreased at three companies and the course of the HRQoL was advantageous at two of the companies as compared to a gainfully employed reference group . A significant decrease in sick leave was revealed at one company , whereas a break in an ascending sick-leave trend appeared at a second company as compared to their respective corporate groups . This comprehensive workplace intervention programme appears to have had positive effects on smoking habits , HRQoL and sick leave Disparities in chronic disease risk by occupation call for newapproaches to health promotion . Well Works-2 was a r and omized , controlled study comparing the effectiveness of a health promotion/occupational health program ( HP/OHS ) with a st and ard intervention ( HP ) . Interventions in both studies were based on the same theoretical foundations . Results from process evaluation revealed that a similar number of activities were offered in both conditions and that in the HP/OHS condition there were higher levels of worker participation using three measures : mean participation per activity ( HP : 14.2 % vs. HP/OHS : 21.2 % ) , mean minutes of worker exposure to the intervention/site ( HP : 14.9 vs. HP/OHS : 33.3 ) , and overall mean participation per site ( HP : 34.4 % vs. HP/ OHS : 45.8 % ) . There were a greater number of contacts with management ( HP : 8.8 vs. HP/OHS : 24.9 ) in the HP/ OHS condition . Addressing occupational health may have contributed to higher levels of worker and management participation and smoking cessation among blue-collar workers Objective : PHLAME ’s ( Promoting Healthy Lifestyles : Alternative Models ’ Effects ) objective was to assess and compare two means to promote healthy lifestyles . Methods : Prospect i ve trial among 599 firefighters r and omized by station to 1 ) team-centered curriculum , 2 ) one-on-one motivational interviewing ( MI ) , and 3 ) controls . Assessment included dietary behavior , physical activity , weight , and general well-being at baseline and 12 months . Program effects were determined using an analysis of covariance ( ANCOVA ) based approach , and models for relationships were evaluated with path analysis . Results : Both interventions were acceptable and delivered with high fidelity . The team and MI programs increased fruit and vegetable consumption ( P < 0.01 and 0.05 , respectively ) and general well-being ( P < 0.01 ) . Significantly less weight gain occurred in both ( P < 0.05 ) . A cross-sectional model was consistent with mediation differing between interventions . Conclusions : Both a team-centered and individual-oriented intervention promoted healthy behaviors . The scripted team curriculum is innovative , exportable , and may enlist influences not accessed with individual formats OBJECTIVES This study examined a project design ed to improve the health and wellness of employees of Brabantia , a Dutch manufacturer of household goods , by means of lifestyle changes and changes in working conditions . METHODS The workers at one Brabantia site constituted the experimental group , and the workers from two other sites formed the control group . Biomedical variables , lifestyles , general stress reactions , and quality of work were measured identically in both groups at baseline and 1 , 2 , and 3 years later . During this period , there was continuous registration of absenteeism . RESULTS The interventions brought about favorable short-term changes in terms of health risks , and there were stable effects on working conditions ( especially decision latitude ) and absenteeism . CONCLUSIONS A combination of interventions directed at both lifestyles and the work environment can produce extensive and stable effects on health-related variables , wellness , and absenteeism This study tests the applicability of a participatory behavior-based injury prevention approach integrated with safety culture initiatives . Sixteen small metal industry enterprises ( 10 - 19 employees ) are r and omly assigned to receive the intervention or not . Safety coaching of owners/managers result in the identification of 48 safety tasks , 85 % of which are solved at follow-up . Owner/manager led constructive dialogue meetings with workers result in the prioritization of 29 tasks , 79 % of which are accomplished at follow-up . Intervention enterprises have significant increases on six of eight safety-perception-survey factors , while comparisons increase on only one factor . Both intervention and comparison enterprises demonstrate significant increases in their safety observation scores . Interview data vali date and supplement these results , providing some evidence for behavior change and the initiation of safety culture change . Given that over 95 % of enterprises in most countries have less than 20 employees , there is great potential for adapting this integrated approach to other industries The Healthy Directions – Small Business r and omized , controlled study aim ed to reduce cancer risk among multiethnic workers in small manufacturing businesses by increasing fruit and vegetable consumption , physical activity , and daily multivitamin in take and decreasing consumption of red meat . The intervention incorporated participatory strategies and was built on a social- context ual framework that addressed people with varying cultural background s and literacy levels . In addition , the intervention aim ed to reduce worker exposure to occupational hazards . Process evaluation was conductedusing quantitative and qualitative research methods . Quantitative results showed high levels of worker awareness of and participation in programs . Qualitative findings suggested that management support , worker input , and a history of social interaction between workers and management may have contributed to high participation rates . Future studies need to examine characteristics associated with participation and nonparticipation of both managers and nonmanagers to increase the likelihood of participation and ultimately improve health behavior OBJECTIVES This study assessed the effects of a 2-year integrated health promotion-health protection work-site intervention on changes in dietary habits and cigarette smoking . METHODS A r and omized , controlled intervention study used the work site as the unit of intervention and analysis ; it included 24 predominantly manufacturing work sites in Massachusetts ( 250 - 2500 workers per site ) . Behaviors were assessed in self-administered surveys ( n = 2386 ; completion rates = 61 % at baseline , 62 % at final ) . Three key intervention elements targeted health behavior change : ( 1 ) joint worker-management participation in program planning and implementation , ( 2 ) consultation with management on work-site environmental changes , and ( 3 ) health education programs . RESULTS Significant differences between intervention and control work sites included reductions in the percentage of calories consumed as fat ( 2.3 % vs 1.5 % kcal ) and increases in servings of fruit and vegetables ( 10 % vs 4 % increase ) . The intervention had a significant effect on fiber consumption among skilled and unskilled laborers . No significant effects were observed for smoking cessation . CONCLUSIONS Although the size of the effects of this intervention are modest , on a population wide basis effects of this size could have a large impact on cancer-related and coronary heart disease end points 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 OBJECTIVES The effects of a stress reduction program on Japanese blue-collar workers were investigated using a controlled trial design . METHODS Two blue-collar worksites that showed higher depression scores ( Zung self-rating depression score ) were selected for the intervention group , after a survey of a large electric company in 1985 . Three blue-collar worksites were selected as a reference group whose workers were matched with the workers of the interventive worksites by mean age , worksite size and mean depression scores . A 1-year stress reduction program was conducted in the intervention group from 1986 to 1987 by worksite supervisors . Effects of the stress reduction program were assessed by comparing the initial depression scores , length of sick leave , and systolic and diastolic blood pressures with those after the follow-up . RESULTS The depression scores decreased during the follow-up in the intervention group , while the scores were almost the same in the reference group . An analysis of covariance with repeated measurements indicated a statistically significant intervention ( group x time interaction ) effect after control for gender and age ( P = 0.035 ) . Sick leave in the past year decreased in 1988 only in the intervention group ; generalized logit analysis with repeated measurements indicated a statistically significant intervention effect after control for gender and age ( P = 0.034 ) . No statistically significant intervention effects were observed on systolic and diastolic blood pressures or selected work stressors . CONCLUSIONS A stress reduction program directed towards worksite supervisors can be used to reduce depressive symptoms and sick leave among Japanese blue-collar workers A re source -building group intervention was developed to enhance career management , mental health , and job retention in work organizations . The in-company training program provided employees with better preparedness to manage their own careers . The program activities were universally implemented using an organization-level , 2-trainer model with trainers from the human re sources management and occupational health services . The study was a within-organizations , r and omly assigned field experimental study ; it investigated the impacts of the intervention on immediate career management preparedness and later mental health and intentions to retire early . A total of 718 eligible individuals returned a question naire in 17 organizations and became voluntary participants . The respondents were r and omly assigned to either an intervention ( N = 369 ) or a comparison group ( N = 349 ) . Those in the intervention group were invited to group intervention workshops , whereas those in the comparison group received printed information about career and health-related issues . The 7-month follow-up results showed that the program significantly decreased depressive symptoms and intentions to retire early and increased mental re sources among the group participants compared to the others . The mediation analyses demonstrated that the increase in career management preparedness as a proximal impact of the intervention mediated the longer term mental health effects . Those who benefited most from the intervention as regards their mental health were employees with elevated levels of depression or exhaustion and younger employees , implying additional benefits of a more targeted use of the intervention . The results demonstrated the benefits of the enhancement of individual-level career management and resilience re sources as career and health promotion practice in work organizations |
13,812 | 19,519,733 | Although no single non-invasive test or model developed to date can match that information obtained from actual histology ( i.e. inflammation , fibrosis , steatosis ) , combinations of two modalities of non-invasive methods can reliably differentiate between minimal and significant fibrosis , and thereby avoid liver biopsy in a significant percentage of patients | BACKGROUND Accurate determination of the presence and degree of liver fibrosis is essential for prognosis and for planning treatment of patients with chronic hepatitis C virus ( HCV ) .
Non-invasive methods of assessing fibrosis have been developed to reduce the need for biopsy .
AIM To perform a review of these non-invasive measures and their ability to replace biopsy for assessing hepatic fibrosis in patients with chronic HCV . | Background : Transient elastography ( FibroScan ) is a new , non-invasive , rapid , and reproducible method allowing evaluation of liver fibrosis by measurement of liver stiffness . In cirrhotic patients , liver stiffness measurements range from 12.5 to 75.5 kPa . However , the clinical relevance of these values is unknown . The aim of this prospect i ve study was to evaluate the accuracy of liver stiffness measurement for the detection of cirrhosis in patients with chronic liver disease . Methods : A total of 711 patients with chronic liver disease were studied . Aetiologies of chronic liver diseases were hepatitis C virus or hepatitis B virus infection , alcohol , non-alcoholic steatohepatitis , other , or a combination of the above aetiologies . Liver fibrosis was evaluated according to the METAVIR score . Results : Stiffness was significantly correlated with fibrosis stage ( r = 0.73 , p<0.0001 ) . Areas under the receiver operating characteristic curve ( 95 % confidence interval ) were 0.80 ( 0.75–0.84 ) for patients with significant fibrosis ( F>2 ) , 0.90 ( 0.86–0.93 ) for patients with severe fibrosis ( F3 ) , and 0.96 ( 0.94–0.98 ) for patients with cirrhosis . Using a cut off value of 17.6 kPa , patients with cirrhosis were detected with a positive predictive value and a negative predictive value ( NPV ) of 90 % . Liver stiffness was significantly correlated with clinical , biological , and morphological parameters of liver disease . With an NPV > 90 % , the cut off values for the presence of oesophageal varices stage 2/3 , cirrhosis Child-Pugh B or C , past history of ascites , hepatocellular carcinoma , and oesophageal bleeding were 27.5 , 37.5 , 49.1 , 53.7 , and 62.7 kPa , respectively . Conclusion : Transient elastography is a promising non-invasive method for detection of cirrhosis in patients with chronic liver disease . Its use for the follow up and management of these patients could be of great interest and should be evaluated further BACKGROUND Liver biopsy is thought m and atory for management of patients with hepatitis C virus ( HCV ) infection , especially for staging fibrosis . We aim ed , in our prospect i ve study , to assess the predictive value of a combination of basic serum biochemical markers for diagnosis of clinical ly significant fibrosis ( including early stages ) . METHODS We assessed liver-biopsy patients with detectable HCV by PCR , for eligibility , and took a blood sample on the day of the procedure . The analysis was done in a first-year period for 205 patients and then tested in a second period on 134 patients . We devised a fibrosis index that included the most informative markers ( combined with age and sex ) for the first-year group . 11 serum markers were assessed as well as fibrosis stage : F0=no fibrosis and F1=portal fibrosis ; and for clinical ly significant fibrosis , F2=few septa , F3=many septa , and F4=cirrhosis . Statistical analysis was by logistic regression , neural connection , and receiver-operating characteristic ( ROC ) curves . FINDINGS First-year and second-year patient-group characteristics and biochemical markers did not differ . The overall frequency of clinical ly significant fibrosis was 40 % ( 138 patients ) . The most informative markers were : alpha2 macroglobulin , alpha2 globulin ( or haptoglobin ) , gamma globulin , apolipoprotein A1 , gamma glutamyltranspeptidase , and total bilirubin . The areas ( SD ) under the ROC curves for the first-year ( 0.836 [ 0.430 ] ) and second-year groups ( 0.870 [ 0.340 ] ) did not differ ( p=0.44 ) . With the best index , a high negative predictive value ( 100 % certainty of absence of F2 , F3 , or F4 ) was obtained for scores ranging from zero to 0.10 ( 12 % [ 41 ] of all patients ) , and high positive predictive value ( > 90 % certainty of presence of F2 , F3 , or F4 ) for scores ranging from 0.60 to 1.00 ( 34 % [ 115 ] of all patients ) . INTERPRETATION A combination of basic serum markers could be used to substantially reduce the number of liver biopsies done in patients with chronic HCV infection The aim of this study was to assess the feasibility of using non-invasive MR elastography for determining the stage of liver fibrosis . Twenty-five consecutive patients who had liver biopsy for suspicion of chronic liver disease were included in the study . The stage of fibrosis on the biopsies was assessed according to the METAVIR scoring system from F0 , no fibrosis , to F4 , cirrhosis . MR elastography was performed by transmitting low-frequency ( 65 Hz ) mechanical waves into the liver with a transducer placed at the back of the patients . The MR pulse sequence was a motion-sensitized spin-echo sequence , phase-locked to the mechanical excitation . The phase maps were processed to obtain shear elasticity and shear viscosity maps . The mean hepatic shear elasticity increased with increasing stage of fibrosis . The mean elasticity was 2.24 + /- 0.23 kPa in the 11 patients without substantial fibrosis ( F0-F1 grade s ) , 2.56 + /- 0.24 kPa in the four patients with substantial fibrosis ( F2-F3 ) and 4.68 + /- 1.61 kPa in the 10 patients with cirrhosis ( F4 ) . The differences between groups were statistically significant ( p < or= 0.05 ) . The mean shear viscosity was significantly higher in the patients with cirrhosis ( 5.19 + /- 1.85 Pa x s ) than in the patients without cirrhosis ( 2.39 + /- 0.86 Pa x s in F0-F1 and 2.27 + /- 0.38 Pa x s in F2-F3 patients ) . It is concluded that non-invasive MR elastography is a feasible method to assess the stage of liver fibrosis PURPOSE To prospect ively compare transit times of Levovist and SonoVue in healthy volunteers and patients with biopsy-proved hepatitis C-related liver disease . MATERIAL S AND METHODS Institutional review board approval and informed consent were obtained . Forty patients and 25 healthy volunteers were examined . Subjects fasted , a bolus of SonoVue ( 0.6 mL ) was injected into a cubital fossa vein , and hepatic venous time-intensity profiles were measured with spectral Doppler tracing . This was repeated with two injections of Levovist ( 2 g ) and another injection of SonoVue . Time-intensity curves of spectral Doppler signals of right and middle hepatic veins were analyzed . A sustained signal intensity increase of 10 % above baseline levels indicated hepatic vein transit time ( HVTT ) . Carotid artery audio intensity was measured in volunteers . Analysis of variance and t tests were used for statistical analysis . RESULTS Twelve patients had mild hepatitis ; 18 , moderate or severe hepatitis ; and 10 , cirrhosis . Mean HVTTs in control , mild hepatitis , moderate or severe hepatitis , and cirrhosis groups were 38.3 seconds + /- 2.4 ( st and ard error ) , 47.5 seconds + /- 6.5 , 29.5 seconds + /- 10.8 , and 17.6 seconds + /- 5.0 , respectively , with Levovist ( P < .001 ) and 29.4 seconds + /- 6.9 , 27.4 seconds + /- 9.3 , 22.9 seconds + /- 4.7 , and 16.4 seconds + /- 4.9 , respectively , with SonoVue ( P < .001 ) . HVTT decreased as severity increased at imaging with both contrast agents . There was no significant difference in HVTT between mild and moderate hepatitis groups with SonoVue ; however , there were significant differences in HVTT between all patient groups with Levovist . HVTT of SonoVue was shorter than that of Levovist in all groups ( P < .001 ) except the cirrhosis group ; in this group , HVTT of the two contrast agents was similar ( P = .05 ) . No difference was observed in mean cardiopulmonary transit time for SonoVue or Levovist ( 9.1 seconds + /- 2.4 [ st and ard error ] and 8.4 seconds + /- 2.5 , respectively , P = .18 ) . CONCLUSION HVTT was significantly shorter with SonoVue than with Levovist ; there was no significant difference in cardiopulmonary transit time AIM To evaluate the method of noninvasive transient elastography for assessment of histological stage of liver fibrosis in patients with chronic hepatitis C ( CHC ) . METHODS Two hundred and thirty-seven patients with CHC were included in this study . Liver biopsy was performed under ultrasonography on 217 of the patients , excluding twenty with clear clinical evidence of liver cirrhosis . Fifty subjects without liver disease were enrolled as a control group ( stage 0 ) . Twenty-five patients with sustained virological response ( SVR ) to interferon ( IFN ) therapy were also enrolled . These patients underwent liver biopsy before IFN therapy . Examination of liver stiffness ( LS ) was performed by elastography . RESULTS Medians ( 50 % levels ) of LS were 4.1 ( 3.5 - 4.9 ) , 6.3 ( 4.8 - 8.5 ) , 8.8 ( 6.8 - 12.0 ) , 14.6 ( 10.5 - 18.6 ) , and 22.2 ( 15.4 - 28.0 ) , respectively , in the fibrosis stages 0 - 4 ( P < 0.001 ) . LS was significantly correlated with four serum fibrosis markers . LS values in patients with SVR were 3.8 ( 3.5 - 5.6 ) , 5.2 ( 4.4 - 6.8 ) , 6.8 ( 6.1 - 7.6 ) , and 6.1 ( 3.6 - 7.9 ) , respectively , in the fibrosis stages 1 - 4 . In all stages , LS for patients with SVR was significantly lower than that for patients who did not undergo IFN therapy . LS was significantly correlated with serum concentrations of hyaluronic acid , type IV collagen , type IV collagen 7S , and type III procollagen N peptide . CONCLUSION LS correlated well with the histological stage of fibrosis . Changes in liver fibrosis stage may thus be estimated noninvasively using transient elastography The course of hepatitis C virus ( HCV ) infection carriers with normal/near-normal aminotransferases ( NALT ) is usually mild ; however , in a few , fibrosis progression occurs . We aim ed to verify whether monitoring by liver biopsy might be replaced by noninvasive methods and to identify factors associated with fibrosis progression in patients with persistently normal alanine aminotransferases . We studied 40 untreated HCV-RNA-positive subjects ( 22 male ; median age , 44 years ) , who underwent two liver biopsies , with a median interval of 78.5 months , during which alanine aminotransferase concentrations ( median number of determinations : 12 ) never exceeded 1.2 times the upper normal limit . Within 9 months from the second biopsy , they were tested by the shear elasticity probe ( Fibroscan ) and the artificial intelligence algorithm FibroTest . METAVIR fibrosis scores were analyzed in relationship to demographic , clinical , and viral parameters . Weighted kappa analysis was used to verify whether the results of noninvasive methods agreed with histology . Significant fibrosis ( > or = F2 ) , present at the first biopsy in only one patient ( 2.5 % ) , was observed at the second biopsy in 14 patients ( 35 % ) . At multivariate analysis , excess alcohol consumption in the past ( > 20 g/d ; P = .017 ) and viral load ( > 8.0 x 10(6 ) copies/mL ; P = .021 ) were independent predictors of progression . In identifying patients with significant fibrosis , inter-rater agreement was excellent for Fibroscan ( weighted kappa = 1.0 ) , and poor for FibroTest ( weighted kappa = -0.041 ) . In conclusion , among HCV carriers with NALT , Fibroscan is superior to the FibroTest in the noninvasive identification of fibrosis , for which excess alcohol consumption in the past and high viral load represent risk factors The risk of complications from percutaneous liver biopsy is low , but discomfort is common and complications require hospitalization in approximately 4 % of patients . The optimal method of performing these biopsies is unknown . The goal of our study was to determine whether the use of ultrasonography in the biopsy room immediately prior to or during the procedure would lessen the risk of complications and to compare the safety and efficacy in obtaining tissue by use of a Trucut needle versus an automatic biopsy needle . Between 1992 and 1994 , 836 patients were entered into a r and omized study ( 489 in Rochester , MN ; 347 in Barcelona , Spain ) . Patients were r and omized immediately prior to liver biopsy into four groups : Trucut needle , or automatic biopsy needle , and with or without ultrasonography . Fisher 's Exact Test and a logistic regression model were also used to assess the effect of needle and ultrasonography on the odds for complications . The four biopsy groups were well-matched at entry with respect to age , sex , underlying liver disease , hemoglobin , prothrombin time , and platelet count . The use of ultrasound was associated with a decreased rate of hospitalization for pain , hypotension , or bleeding ( 2 vs. 9 , P < .05 ) . No difference in safety was found between the two types of needles . The number of passes needed to obtain specimens was similar for all four groups . The average length of the specimen was slightly greater with ultrasonographic-guided biopsies ( 1.7 mm vs. 1.6 mm , P < .05 ) and with biopsies obtained using the automatic biopsy needle when compared with the Trucut needle ( 1.7 mm vs. 1.5 mm , P < .05 ) , but this did not seem to be clinical ly important . The addition of ultrasonography reduces complications in patients undergoing percutaneous liver biopsy . The type of needle appears to offer little difference in safety or yield of diagnostic tissue . The use of ultrasonography for guidance of percutaneous liver biopsy will lead to a lower rate of complications . The value of this benefit must be weighed against the added cost of ultrasonographic guidance OBJECTIVES : Fibrotest ( FT ) and Actitest ( AT ) are biochemical markers of fibrosis and activity for use as a non-invasive alternative to liver biopsy in patients with chronic hepatitis C virus ( HCV ) . The aim of this study was to perform an external validation of FT and AT and to study the discordances between FT/AT and liver biopsy in patients with chronic hepatitis C. METHODS : A total of 519 consecutive patients with chronic HCV were prospect ively included in five centers , with liver biopsy and biochemical markers taken at the same day . Fifteen patients were excluded because their biopsies could not be interpreted . Diagnostic accuracies were assessed by receiver operating characteristic ( ROC ) curve analysis . RESULTS : Median biopsy size was 15 mm ( range : 2–58 ) , with 9 portal tracts ( 1–37 ) and 1 fragment ( 1–12 ) . 46 % ( 230/504 ) were classified F2–F4 in fibrosis and 39 % A2–A3 in activity . FT area under ROC curve for diagnosis of activity ( A2–A3 ) , significant fibrosis ( F2–F4 ) , and severe fibrosis ( F3–F4 ) were 0.73 [ 0.69–0.77 ] , 0.79 [ 0.75–0.82 ] , and 0.80 [ 0.76–0.83 ] , respectively . Among the 92 patients ( 18 % ) with 2 fibrosis stages of discordance between FT and biopsy , the discordance was attributable to FT in 5 % of cases , to biopsy in 4 % , and undetermined in 9 % . CONCLUSIONS : This prospect i ve independent and multicenter study confirms the diagnostic value of FT and AT found in the princeps study and suggests that FT and AT can be an alternative to biopsy in most patients with chronic HCV BACKGROUND / AIMS In chronic hepatitis C , biopsy is the gold st and ard for assessment of liver fibrosis . Non-invasive markers have been proposed but their use is limited by diagnostic accuracy . Our aim was to increase the diagnostic performance of non-invasive markers of liver fibrosis by combining them in sequential algorithms . METHODS One hundred and ninety patients with chronic hepatitis C were evaluated for AST to platelets ratio ( APRI ) , Forns ' index and Fibrotest at the time of liver biopsy and stepwise combination algorithms were developed and vali date d prospect ively in 100 additional patients . RESULTS Three algorithms were developed : ( 1 ) significant fibrosis ( F > or=2 by METAVIR ) was identified with high diagnostic performance ( > 94 % accuracy ) using APRI as screening test , followed by Fibrotest in APRI non-classified cases and restricting liver biopsy to patients classified F0-F1 by non-invasive tests . ( 2 ) A slightly modified algorithm had similar performance when applied to hepatitis C carriers with normal ALT . ( 3 ) Identification of cirrhosis ( 95 % accuracy ) was achieved using a dedicated algorithm with different cut-off , reducing by 60 - 70 % the liver biopsies needed . CONCLUSIONS Stepwise combination of non-invasive markers of liver fibrosis improves the diagnostic performance in chronic hepatitis C. Need for liver biopsy is reduced by 50 - 70 % but can not be completely avoided Goals To evaluate the aspartate aminotransferase/platelet ratio index ( APRI ) as a predictor of the presence or absence of significant fibrosis on liver biopsy of patients with chronic hepatitis C ( HCV ) . Background The decision to treat HCV is often made on the basis of the presence or absence of significant fibrosis on the liver biopsy . Because liver biopsy is expensive and invasive a noninvasive marker to evaluate hepatic fibrosis would be useful . The APRI is an easy to calculate index that is one of several markers that have been proposed . Study We retrospectively review ed the charts of 339 patients with chronic HCV who had liver biopsies from January 2000 to March 2003 . We subsequently evaluated 151 patients receiving pretreatment evaluation liver biopsies who had serum aspartate aminotransferase , platelets , routine liver function tests , and demographic data obtained . All liver biopsies were staged by the Batts Ludwig criteria . Results The area under the curve of the receiver operator characteristics of the calculated APRI compared with the liver biopsy demonstrated that the fibrosis score was 0.889 in the prospect i ve group and 0.790 in the retrospective group . To achieve predictive values of approximately 90 % , useful cutoffs were found at 0.40 and 1.5 in the retrospective study , and 0.42 and 1.2 in the prospect i ve study leaving intermediate zones of 58.9 % and 41.1 % , respectively . In the prospect i ve group , 34 of 36 patients with a value of < 0.42 were accurately predicted as having mild fibrosis , whereas 50 of 54 patients with a value > 1.2 were accurately predicted to have significant fibrosis . Conclusions The APRI is a good estimator of hepatic fibrosis and was more accurate in a prospect i ve group than a retrospective one . It potentially could be used to decrease the number of liver biopsies BACKGROUND FibroTest , a noninvasive method of measuring biomarkers of liver fibrosis , is an alternative to liver biopsy for determining the severity of chronic hepatitis C virus ( HCV ) infection . We compared the 5-year prognostic value of the FibroTest with biopsy staging for predicting cirrhosis decompensation and survival in patients with chronic HCV infection . METHODS Fibrosis stage was assessed on the same day by FibroTest and biopsy in a prospect i ve cohort of 537 patients . Disease classification at baseline was 157 patients with severe fibrosis ( FibroTest > 0.58 ) , 137 with moderate fibrosis ( FibroTest 0.32 - 0.58 ) , and 243 with no or minimal fibrosis ( FibroTest < 0.32 ) . RESULTS In 64 untreated patients with severe fibrosis , survival without HCV complications was 73 % [ 95 % confidence interval ( CI ) , 59%-086 % ; 13 complications ] , and survival without HCV-related death was 85 % ( 95 % CI , 73%-96 % ; 7 HCV deaths ) . Survival rates were higher in patients with moderate fibrosis , [ 99 % ( 95 % CI , 97%-100 % ; 1 complication ; P < 0.001 ) and 100 % ( no HCV death ; P < 0.001 ) for patients with and without HCV-related complications , respectively ] , and in patients with minimal fibrosis [ 100 % ( no complication ; P < 0.001 vs severe ) and 100 % ( no HCV death ; P < 0.001 vs severe ) , respectively ] . FibroTest was a better predictor than biopsy staging for HCV complications , with area under the ROC curves ( AUROC ) = 0.96 ( 95 % CI , 0.93%-0.97 % ) vs 0.91 ( 95 % CI , 0.85%-0.94 % ; P = 0.01 ) , respectively ; it was also a better predictor for HCV deaths : AUROC = 0.96 ( 95 % CI , 0.93%-0.98 % ) vs 0.87 ( 95 % CI , 0.70%-0.94 % ; P = 0.046 ) , respectively . The prognostic value of FibroTest was still significant ( P < 0.001 ) in multivariate analyses after taking into account histology , treatment , alcohol consumption , and HIV coinfection . CONCLUSION The FibroTest measurement of HCV biomarkers has a 5-year prognostic value similar to that of liver biopsy PURPOSE To develop a method for measuring liver stiffness with magnetic resonance ( MR ) elastography and to prospect ively test this technique in healthy volunteers and patients with liver fibrosis . MATERIAL S AND METHODS This HIPAA-compliant study was approved by an institutional review board , and informed consent was obtained from each subject . First , to determine the feasibility of applying shear waves to the liver , a pneumatic acoustic wave generator was developed and tested by using a tissue-simulating gel phantom with ribs on one side and without ribs on the other . The effect of interposed ribs on stiffness measurements was tested . Then , liver stiffness was measured with MR elastography in 12 healthy volunteers ( eight men , four women ; mean age , 26.7 years ; age range , 19 - 39 years ) by using the subcostal approach and the transcostal approach and in 12 patients with chronic liver disease ( six men , six women ; mean age , 50.5 years ; age range , 36 - 60 years ) by using the transcostal approach . Various statistical analyses were performed to assess all measurements . RESULTS Ex vivo , interposed ribs reduced shear wave amplitude but did not hinder stiffness measurements . In volunteers , the transcostal approach surprisingly yielded better shear waves in the liver than did the subcostal approach . The mean liver shear stiffness was significantly lower in volunteers ( mean , 2.0 kPa + /- 0.3 [ st and ard deviation ] ) than it was in patients with liver fibrosis ( mean , 5.6 kPa + /- 5.0 ; median , 3.7 kPa ; range , 2.7 - 19.2 kPa ; P < .001 ) . CONCLUSION MR elastography of the liver is feasible and shows promise as a quantitative method for noninvasive assessment of liver fibrosis To determine the sensitivity , specificity , and predictive values of the sonographic analysis of liver surface irregularities for the diagnosis of cirrhosis , the authors conducted a prospect i ve and blinded study in 70 subjects with abnormal liver function tests . All patients included underwent liver biopsy within 15 days of the sonographic study . Twenty-three subjects with no signs or symptoms of liver disease were examined to assess the sonographic appearance of normal liver surface . Studies were performed with a small-parts probe , high-frequency transducer ( 7.5 MHz ) . Three basic patterns of liver surface were found : type I , normal ; type II , focal abnormality ; and type III , diffuse irregularity . Considering diffuse surface irregularity as an objective sonographic sign of cirrhosis , the study 's sensitivity was 87.5 % , specificity 81.5 % , and positive and negative predictive values were 80 % and 88.5 % , respectively . Disease prevalence for cirrhosis was 45 % . We conclude that sonographic analysis of the liver surface is a useful noninvasive test for the diagnosis of cirrhosis in the appropriate clinical setting BACKGROUND The degree of liver fibrosis in patients with Hepatitis C ( HCV ) provides important prognostic information ; however , the only current method available to obtain this information is by performing a liver biopsy . Liver biopsies are invasive , associated with complications , and costly . There has been recent interest in developing a panel of serum markers that can reliably predict the presence of fibrosis and , thus , obviate the need for a liver biopsy . Our objective was to prospect ively vali date a panel of serum fibrosis markers ( FIBROSpect(SM ) II ) that has been recently developed . METHODS Serum was obtained from 108 consecutive HCV ( 15 % with HCV/ETOH ) patients seen in a hepatology clinic at a single tertiary care center at the time of liver biopsy . The performance of FIBROSpect II ( consisting of 3 fibrosis markers : hyaluronic acid , tissue inhibitor of metalloproteinases 1 , and alpha-2-macroglobulin ) in differentiating mild ( F0-F1 ) from significant ( F2-F4 ) fibrosis was assessed by comparing the panel results with performed liver biopsy . RESULTS The prevalence of significant fibrosis in the study group was 36.1 % . The diagnostic value of the serum marker panel to detect significant fibrosis as assessed by area under the receiver operating characteristic ( ROC ) curve was 0.826 . Performance characteristics are as follows : sensitivity 71.8 % , specificity 73.9 % , positive predictive value 60.9 % , negative predictive value 82.3 % , and overall accuracy of 73.1 % . CONCLUSION This prospect i ve study supports the clinical utility of serum markers in detecting fibrosis and vali date s the performance of FIBROSpect II in a prospect i ve cohort of patients . The high negative predictive value of the test provides a reliable alternative to rule out severe fibrosis Summary Background Recent studies strongly suggest that due to the limitations and risks of biopsy , as well as the improvement of the diagnostic accuracy of biochemical markers , liver biopsy should no longer be considered m and atory in patients with chronic hepatitis C. In 2001 , FibroTest ActiTest ( FT-AT ) , a panel of biochemical markers , was found to have high diagnostic value for fibrosis ( FT range 0.00–1.00 ) and necroinflammatory histological activity ( AT range 0.00–1.00 ) . The aim was to summarize the diagnostic value of these tests from the scientific literature ; to respond to frequently asked questions by performing original new analyses ( including the range of diagnostic values , a comparison with other markers , the impact of genotype and viral load , and the diagnostic value in intermediate levels of injury ) ; and to develop a system of conversion between the biochemical and biopsy estimates of liver injury . Results A total of 16 publications were identified . An integrated data base was constructed using 1,570 individual data , to which applied analytical recommendations . The control group consisted of 300 prospect ively studied blood donors . For the diagnosis of significant fibrosis by the METAVIR scoring system , the areas under the receiver operating characteristics curves ( AUROC ) ranged from 0.73 to 0.87 . For the diagnosis of significant histological activity , the AUROCs ranged from 0.75 to 0.86 . At a cut off of 0.31 , the FT negative predictive value for excluding significant fibrosis ( prevalence 0.31 ) was 91 % . At a cut off of 0.36 , the ActiTest negative predictive value for excluding significant necrosis ( prevalence 0.41 ) was 85 % . In three studies there was a direct comparison in the same patients of FT versus other biochemical markers , including hyaluronic acid , the Forns index , and the APRI index . All the comparisons favored FT ( P < 0.05 ) . There were no differences between the AUROCs of FT-AT according to genotype or viral load . The AUROCs of FT-AT for consecutive stages of fibrosis and grade s of necrosis were the same for both moderate and extreme stages and grade s. A conversion table was constructed between the continuous FT-AT values ( 0.00 to 1.00 ) and the expected semi-quantitative fibrosis stages ( F0 to F4 ) and necrosis grade s ( A0 to A3 ) . Conclusions Based on these results , the use of the biochemical markers of liver fibrosis ( FibroTest ) and necrosis ( ActiTest ) can be recommended as an alternative to liver biopsy for the assessment of liver injury in patients with chronic hepatitis C. In clinical practice , liver biopsy should be recommended only as a second line test , i.e. , in case of high risk of error of biochemical tests BACKGROUND The FibroTest and ActiTest are noninvasive biochemical markers of liver injury that are intended for use as alternatives to liver biopsy in patients with chronic hepatitis C. The aims of this study were to assess the quality of biopsy and the prevalence of discordances between biopsy and markers , to identify factors associated with discordances , and to attribute these discordances to either markers or biopsy failure . METHODS Fibrosis stage and activity grade were prospect ively assessed on the same day by a liver biopsy and by markers . On the basis of risk factors for failure and independent endpoints , discordance was classified as being attributable to biopsy or to markers . RESULTS Only 74 of 537 patients ( 14 % ) had a biopsy size > or = 25 mm . Discordance was observed in 154 of 537 patients ( 29 % ) , including 16 % for fibrosis staging and 17 % for activity grading . Steatosis , an inflammatory profile , and biopsy size were associated with discordance . Discordance was attributable to failure of markers in 13 patients ( 2.4 % ) and to biopsy failure in 97 ( 18 % ; P < 0.001 vs Fibrotest and Actitest ) , and was nonattributable in 44 patients ( 8.2 % ) . The most frequent failures attributable to markers were false negatives ( 1.3 % ) attributable to inflammation . The most frequent failures attributable to biopsy were false negatives of activity grading ( 10.1 % ) and of fibrosis staging ( 4.5 % ) , both associated with smaller biopsy size and steatosis . False positives of fibrosis staging ( 3.5 % ) were associated with fragmented biopsies . CONCLUSION In this series , the size of liver biopsy is adequate in only a minor proportion ( approximately 14 % ) of patients with chronic hepatitis C. When biopsy and marker results are discordant , a reason can be identified in more than two-thirds of cases and , in those cases , biopsy failure is > 7 times more common than diagnostic failure of markers Liver biopsy remains the gold st and ard in the assessment of severity of liver disease . Noninvasive tests have gained popularity to predict histology in view of the associated risks of biopsy . However , many models include tests not readily available , and there are limited data from patients with HIV/hepatitis C virus ( HCV ) coinfection . We aim ed to develop a model using routine tests to predict liver fibrosis in patients with HIV/HCV coinfection . A retrospective analysis of liver histology was performed in 832 patients . Liver fibrosis was assessed via Ishak score ; patients were categorized as 0 - 1 , 2 - 3 , or 4 - 6 and were r and omly assigned to training ( n = 555 ) or validation ( n = 277 ) sets . Multivariate logistic regression analysis revealed that platelet count ( PLT ) , age , AST , and INR were significantly associated with fibrosis . Additional analysis revealed PLT , age , AST , and ALT as an alternative model . Based on this , a simple index ( FIB-4 ) was developed : age ( [ yr ] x AST [ U/L ] ) / ( ( PLT [ 10(9)/L ] ) x ( ALT [U/L])(1/2 ) ) . The AUROC of the index was 0.765 for differentiation between Ishak stage 0 - 3 and 4 - 6 . At a cutoff of < 1.45 in the validation set , the negative predictive value to exclude advanced fibrosis ( stage 4 - 6 ) was 90 % with a sensitivity of 70 % . A cutoff of > 3.25 had a positive predictive value of 65 % and a specificity of 97 % . Using these cutoffs , 87 % of the 198 patients with FIB-4 values outside 1.45 - 3.25 would be correctly classified , and liver biopsy could be avoided in 71 % of the validation group . In conclusion , noninvasive tests can accurately predict hepatic fibrosis and may reduce the need for liver biopsy in the majority of HIV/HCV-coinfected patients Purpose The aims of this prospect i ve study were to evaluate analysis of sulfur-hexafluoride-filled microbubble contrast agent ( Sonovue ) transit times as a tool for differentiating liver cirrhosis from the noncirrhotic stage of liver disease and to compare its performance with that of conventional B-mode and Doppler ultrasonography ( US ) . Material s and methods Contrast-enhanced hepatic ultrasonography with the US contrast agent Sonovue was performed on 38 patients with diagnoses of hepatic cirrhosis based on unequivocal clinical signs or liver biopsy findings ( Child-Pugh classes A in 19 , B in 16 and C in three ) , 31 patients with noncirrhotic diffuse liver disease ( biopsy confirmed ) and 14 controls without diffuse liver disease . Time curves of hepatic-vein signal intensity were analysed using objective criteria to determine the time of enhancement onset ( hepatic-vein arrival time ) and peak enhancement ( hepatic-vein peak enhancement ) . Accuracy in diagnosing cirrhosis was compared with that based on B-mode and Doppler data . Results Hepatic-vein arrival time in cirrhotic patients was significantly shorter ( p<0.01 ) than in noncirrhotic ( chronic liver disease and controls ) patients . Peak enhancement times in these three groups were not significantly different . An arrival-time cutoff of 17 s distinguished cirrhotic from noncirrhotic patients with high accuracy ( 100 % sensitivity , 93.3 % specificity , positive and negative predictive values 92.6 % and 100 % , respectively ) and excellent reproducibility ( kappa coefficients of 1.0 and 0.93 for intra and interobserver agreement ) . Contrast-enhanced US showed better sensitivity than the B-mode and Doppler data . Conclusions Analysis of the time of onset of US contrast enhancement of the hepatic vein appears to be a potentially useful noninvasive supplement to conventional sonography and Doppler in the follow-up of patients with chronic diffuse liver disease . RiassuntoObiettivoLo scopo di questo studio prospettico è stato quello di valutare l’analisi del tempo di transito delle microbolle di mezzo di contrasto costituito da esafluoruro di zolfo ( Sonovue ) come mezzo per differenziare la cirrosi epatica dagli stadi non cirrotici di malattia e di comparare la sua performance con quella dell’esame B-mode st and ard e Doppler . Material i e metodiÈ stato effettuato l’esame ecografico del fegato con mezzo di contrasto Sonovue in 38 pazienti con diagnosi di cirrosi basata su segni clinici inequivocabili o su biopsia epatica ( Child-Pugh A in 19 pazienti , B in 16 e C in 3 ) . Sono stati analizzati inoltre 31 pazienti con patologia cronica diffusa non cirrotica ( confermata dalla biopsia ) , e 14 pazienti di controllo senza patologia epatica . Sono stati analizzati i diagrammi tempo/intensità di segnale della vena sovraepatica utilizz and o criteri oggettivi per determinare il tempo di inizio dell’enhancement ( tempo di arrivo della vena sovraepatica ) e il picco di enhancement ( tempo di picco della vena sovraepatica ) . L’accuratezza nella diagnosi di cirrosi è stata confrontata con quella basata sui dati B-mode e Doppler . RisultatiIl tempo di arrivo della vena sovraepatica nei pazienti cirrotici è risultato significativamente pi`u breve ( p<<0,01 ) rispetto ai pazienti non cirrotici ( patologia epatica cronica e controlli ) . Il tempo di picco di enhancement in questi tre gruppi non è risultato significativo . Un tempo cut-off di arrivo di 17 secondi ha distinto pazienti cirrotici da quelli non cirrotici con elevata accuratezza ( 100 % sensitività , 93,3 % specificità , valore predittivo positivo e negativo : 92,6 % e 100 % , rispettivamente ) ed eccellente riproducibilità ( coefficiente κ di 1,0 e 0,93 per l’accordo intra-ed interosservatore ) . L’ecografia con mezzo di contrasto ha mostrato una migliore sensibilità rispetto all’esame B-mode e Doppler . Conclusion iL’analisi del tempo di inizio dell’enhancement contrastografico della vena sovraepatica appare un potenziale e non invasivo supplemento all’ecografia convenzionale e all’esame Doppler nel follow-up di pazienti con patologia epatica cronica diffusa BACKGROUND & AIMS Liver stiffness measurement ( LSM ) with transient elastography ( Fibroscan ) can accurately diagnose advanced liver fibrosis , but its performance in early liver fibrosis is less satisfactory . We aim ed to study the diagnostic performance of LSM for histologic bridging fibrosis and cirrhosis in various chronic liver diseases and to investigate the effects of liver fibrosis distribution on LSM . METHODS We prospect ively studied consecutive patients with chronic liver diseases undergoing liver biopsy and transient elastography examinations . Morphometric analysis was performed to evaluate the distribution of liver fibrosis . RESULTS One hundred thirty-three patients ( 50 % chronic hepatitis B , 14 % chronic hepatitis C , and 24 % nonalcoholic fatty liver disease ) were studied . Morphometric analysis revealed a higher correlation between LSM and pericellular fibrosis ( r = 0.43 ) than periportal ( r = 0.21 ) or perivenular fibrosis ( r = 0.25 ) . Area under receiver operating characteristic curve ( ROC ) of LSM for bridging fibrosis was 0.87 ( 95 % confidence interval , 0.81 - 0.93 ) and for cirrhosis was 0.89 ( 95 % confidence interval , 0.83 - 0.94 ) . Higher LSM was associated with higher serum ALT level . Patients with the same fibrosis staging but higher ALT levels tend to have higher LSM . The area under ROC curve of LSM for cirrhosis was lower among patients who had ALT above the upper limit of normal ( 0.86 ) as compared with that of patients with normal ALT levels ( 0.93 , P = .03 ) . CONCLUSIONS Transient elastography can diagnose severe fibrosis because of its good correlation with pericellular fibrosis . Transient elastography might overestimate liver fibrosis when ALT is elevated BACKGROUND AND AIMS Chronic hepatitis C is a slowly progressing inflammatory disease of the liver that can lead to cirrhosis and its complications . Assessment of liver damage in hepatitis C has been primarily via histological evaluation . Liver biopsy , while useful in determining the extent of liver damage , has associated costs and places patients at a small but finite risk of bleeding . Studies in small patient population s have identified serum markers shown to correlate with liver histology , including procollogen III peptide and hyaluronic acid ( HA ) . To determine whether serum HA was a reliable predictor of cirrhosis and fibrosis , we examined serum HA concentrations from 486 chronic Hepatitis C virus ( HCV ) patients . METHODS AND RESULTS Patients were anti-HCV and HCV RNA positive , with elevated alanine aminotransferase values and underwent a liver biopsy . Sera were obtained at the baseline for HA using radioimmunoassay methodology . Patients with cirrhosis had significantly higher serum HA concentrations compared with non-cirrhotic patients ( 382+/-31 vs 110+/-9 microg/L respectively , P < 0.001 ) . Patients with fibrosis had significantly higher mean serum HA concentrations ( 179+/-11 microg/L ) compared with patients without fibrosis ( 62+/-20 microg/L ; P < 0.001 ) . The correlation between HA concentration and the components of the Knodell histological activity index score revealed no strong associations with the exception of fibrosis , which showed moderate correlation ( R=0.5421 , P<0.001 ) . The clinical value of HA measurement appears to be its ability to exclude cirrhosis . A HA value of < 60 microg/L excluded the presence of cirrhosis or significant fibrosis with a predictive value of 99 and 93 % , respectively . CONCLUSIONS Serum HA measurement may be clinical ly useful to non-invasively assess the degree of fibrosis and cirrhosis . Further prospect i ve studies are warranted to determine the clinical utility of HA as a non-invasive marker of liver fibrosis A proper diagnosis of cirrhosis is essential for the management of patients with chronic liver diseases . We assessed the accuracy of liver stiffness measurement by Fibroscan for the diagnosis of cirrhosis in 1,257 patients with chronic liver diseases of various causes enrolled in a prospect i ve multicenter study as well as clarified causes of discrepancies between liver histology and Fibroscan . One hundred thirty‐two patients had unsuitable biopsy specimens , and 118 had unreliable liver stiffness measurements . Because 232 patients overlapped with a previous study , analysis was performed in the 775 new patients then derived in the whole population ( 1,007 ; 165 cirrhosis ) . Diagnostic accuracy was assessed by receiver operator curve ( ROC ) analysis . Liver sample s were re‐analyzed in case of discrepancies . The area under the ROC ( AUROC ) was 0.95 ( 95 % CI , 0.93‐0.96 ) for the diagnosis of cirrhosis in either 775 or 1,007 patients . The cutoff value with optimal diagnosis accuracy was 14.6 kPa in 1,007 patients ( positive and negative predictive values , 74 % and 96 % ) with discrepancies among the etiological groups . Eighty patients were misclassified : ( 1 ) among 45 patients without cirrhosis with liver stiffness 14.6 kPa or greater , 27 ( 60 % ) had extensive fibrosis and 10 ( 22 % ) significant perisinusoidal fibrosis ; and ( 2 ) among 35 patients with cirrhosis and liver stiffness less than 14.6 kPa , 10 ( 29 % ) had a macronodular pattern and 25 ( 71 % ) either none or mild activity . In conclusion , Fibroscan is a reliable method for the diagnosis of cirrhosis in patients with chronic liver diseases , better at excluding than at predicting cirrhosis using a threshold of 14.6 kPa . False‐negatives are mainly attributable to inactive or macronodular cirrhosis . ( HEPATOLOGY 2006;44:1511–1517 . Background : Noninvasive markers of hepatic fibrosis hold great promise to stage liver fibrosis and to monitor disease progression . To date , few studies have assessed the performance of the currently available markers of hepatic fibrosis in HIV-infected cohorts . The aim of the current study was to compare the diagnostic performance and characteristics of a number of noninvasive markers of hepatic fibrosis in population s of hepatitis C virus (HCV)-infected patients with and without HIV infection . Methods : A sample of 97 subjects ( 40 HCV/HIV-coinfected , 57 HCV-infected ) undergoing liver biopsy as part of an ongoing prospect i ve cohort study was evaluated . Liver biopsies were assessed by a single hepatopathologist and scored according to Ishak criteria . Noninvasive markers of fibrosis studied included international normalized ratio , platelet count , aspartate aminotransferase (AST)/alanine aminotransferase ratio , AST platelet ratio index ( APRI ) , Forns index , procollagen III N peptide , hyaluronic acid , and YKL-40 . Results : The correlations between fibrosis markers with the stage of fibrosis and the diagnostic performance of each of the tests were similar in the groups with and without HIV infection . Although a trend to improved diagnostic performance in the HCV/HIV-coinfected group was observed , this may be related to the small sample size . Conclusions : The diagnostic performance of the evaluated noninvasive markers of liver fibrosis is equivalent in HCV/HIV-coinfected and HCV-infected subjects . These tests may be of value for the clinical evaluation of HCV/HIV-coinfected patients and warrant further study Background and aims : A reliable non-invasive assessment of the severity of diffuse liver disease is much needed . We investigated the utility of hepatic vein transit times ( HVTT ) for grading and staging diffuse liver disease in a cohort of patients with hepatitis C virus ( HCV ) infection using an ultrasound microbubble contrast agent as a tracer . Material s and methods : Eighty five untreated patients with biopsy proven HCV induced liver disease were studied prospect ively . All were HCV RNA positive on polymerase chain reaction testing . Based on their histological fibrosis ( F ) and necroinflammatory ( NI ) scores , untreated patients were divided into mild hepatitis ( F ⩽2/6 , NI ⩽3/18 ) , moderate/severe hepatitis ( 3 ⩽F < 6 or NI ⩾4 ) , and cirrhosis ( F = 6/6 ) groups . In addition , 20 age matched healthy volunteers were studied . After an overnight fast , a bolus of contrast agent ( Levovist ) was injected into an antecubital vein and spectral Doppler signals were recorded from both the right and middle hepatic veins for analysis . HVTTs were calculated as the time from injection to a sustained rise in Doppler signal > 10 % above baseline . The Doppler signals from the carotid artery were also measured in 60 patients and carotid delay times ( CDT ) calculated as the difference between carotid and hepatic vein arrival times . The earliest HVTT in each patient was used for analysis . Results : Mean ( SEM ) HVTT for the control , mild hepatitis , moderate/severe hepatitis , and cirrhosis groups showed a monotonic decrease of 38.1 ( 2.8 ) , 38.8 ( 2.4 ) , 26.0 ( 2.4 ) , and 15.8 ( 0.8 ) seconds , respectively . Mean ( SEM ) CDT for the control , mild hepatitis , moderate/severe hepatitis , and cirrhosis patients again showed progressive shortening of 30.3 ( 2.6 ) , 25.9 ( 2.6 ) , 14.8 ( 2.1 ) , and 5.6 ( 1.2 ) seconds , respectively . There were significant differences between the groups for HVTT ( ANOVA , p<0.001 ) and CDT ( ANOVA , p<0.001 ) . There was 100 % sensitivity and 80 % specificity for diagnosing cirrhosis and 95 % sensitivity and 86 % specificity for differentiating mild hepatitis from more severe liver disease . Conclusion : We have shown , for the first time , that HVTT using an ultrasound microbubble contrast agent can assess HCV related liver disease with clear differentiation between mild hepatitis and cirrhosis . There were significant differences between these two groups and the moderate/severe hepatitis group . CDT offers no additional benefit or greater differentiation than HVTT and can be omitted , thus simplifying this technique . HVTT may complement liver biopsy and may also be a useful alternative for assessment of liver disease in patients who have contraindications to biopsy 1 Noninvasive tests for the staging of chronic hepatitis C virus ( HCV ) infection would be an attractive alternative to liver biopsy . The 13C‐aminopyrine breath test ( ABT ) has been proposed for the noninvasive assessment of hepatic function and partly correlates with fibrosis . We aim ed to investigate causes for the lack of discriminatory power for different degrees of hepatic fibrosis . 2 Eighty‐three patients ( median age 49 years ( 28–78 years ) ) with chronic HCV infection underwent the ABT after an oral load of 75 mg N , N‐dimethyl‐13C‐aminopyrine . Portal vein flow was assessed by duplex‐Doppler and a laboratory index ( aspartate aminotransferase to platelet ratio index or APRI ) was calculated . Parameters were compared with liver histology . 3 The cumulative 13C‐recovery differed significantly between patients without relevant fibrosis ( fibrosis score 0–2 ) and cirrhosis ( 5–6 ) , beginning after 30 min of sampling ( P < 0.05 ) . The ABT did not discriminate patients with fibrosis scores 3–4 from the remaining two patient groups . Sensitivity and specificity for the prediction of cirrhosis was 73.4–82.8 % and 63.2–68.4 % , depending on the sampling time . Compared with the fibrosis score ( P = 0.04 ) , patient age was a highly significant independent predictor for the 13C‐recovery ( P < 0.0001 ) . Aspartate aminotransferase to platelet ratio index and duplex‐Doppler predicted cirrhosis with 76.6%vs . 87.5 % sensitivity and 63.2%vs . 68.4 % specificity . 4 Our data suggest an age‐dependent decrease of cytochrome P450 activity which probably accounts for the large overlap of ABT results that preclude clear differentiation . This is also consistent with former pharmacodynamic trials . Age‐adapted reference ranges could improve ABT results Liver fibrosis is the main predictor of the progression of chronic hepatitis C , and its assessment by liver biopsy ( LB ) can help determine therapy . However , biopsy is an invasive procedure with several limitations . A new , noninvasive medical device based on transient elastography has been design ed to measure liver stiffness . The aim of this study was to investigate the use of liver stiffness measurement ( LSM ) in the evaluation of liver fibrosis in patients with chronic hepatitis C. We prospect ively enrolled 327 patients with chronic hepatitis C in a multicenter study . Patients underwent LB and LSM . METAVIR liver fibrosis stages were assessed on biopsy specimens by 2 pathologists . LSM was performed by transient elastography . Efficiency of LSM and optimal cutoff values for fibrosis stage assessment were determined by a receiver-operating characteristics ( ROC ) curve analysis and cross-vali date d by the jack-knife method . LSM was well correlated with fibrosis stage ( Kendall correlation coefficient : 0.55 ; P < .0001 ) . The areas under ROC curves were 0.79 ( 95 % CI , 0.73 - 0.84 ) for F > or = 2 , 0.91 ( 0.87 - 0.96 ) for F > or =3 , and 0.97 ( 0.93 - 1 ) for F=4 ; for larger biopsies , these values were , respectively , 0.81 , 0.95 , and 0.99 . Optimal stiffness cutoff values of 8.7 and 14.5 kPa showed F > or = 2 and F=4 , respectively . In conclusion , noninvasive assessment of liver stiffness with transient elastography appears as a reliable tool to detect significant fibrosis or cirrhosis in patients with chronic hepatitis Liver biopsy remains the gold st and ard for characterizing diffuse liver disease and is associated with significant morbidity and , rarely , mortality . Our aim was to investigate whether a noninvasive technique , in vivo phosphorus 31 ( (31)P)-magnetic resonance spectroscopy ( MRS ) , could be used to assess the severity of hepatitis C virus (HCV)-related liver disease . Fifteen healthy controls and 48 patients with biopsy-proven HCV-related liver disease were studied prospect ively . Based on their histologic fibrosis ( F ) and necroinflammatory ( NI ) scores , patients were divided into mild hepatitis ( F < or= 2/6 , NI < or= 3/18 ) , moderate/severe hepatitis ( 3 < or= F < 6 or NI > or= 4/18 ) , and cirrhosis ( F = 6/6 ) . Hepatic (31)P MR spectra were obtained using a 1.5-T spectroscopy system . Quantitation of the (31)P signals was performed in the time domain using the Advanced MAgnetic RESonance algorithm . There was a monotonic increase in the mean + /- 1 st and ard error phosphomonoester ( PME ) to phosphodiester ( PDE ) ratios for the control , mild disease , moderate disease , and cirrhosis groups : 0.15 + /- 0.01 , 0.18 + /- 0.02 , 0.25 + /- 0.02 , 0.38 + /- 0.04 , respectively ( ANOVA , P < .001 ) . An 80 % sensitivity and specificity was achieved when using a PME/PDE ratio less than or equal to 0.2 to denote mild hepatitis and a corresponding ratio greater than or equal to 0.3 to denote cirrhosis . No other significant spectral changes were observed . In conclusion , (31)P MRS can separate mild from moderate disease and these 2 groups from cirrhosis . The ability to differentiate these population s of patients has therapeutic implication s and (31)P MRS , in some situations , would not only complement a liver biopsy but could replace it and be of particular value in assessing disease progression Performing a liver biopsy in patients infected with HIV and hepatitis C virus ( HCV ) is considered the st and ard of practice to assess hepatic involvement but carries risks to patients . This pilot study was design ed to identify single photon emission computed tomography ( SPECT ) parameters that correlate with liver disease stage . HIV-coinfected and HCV-coinfected individuals undergoing a liver biopsy had a SPECT scan performed . The results showed that a number of SPECT parameters were associated with histologic changes in architecture , fibrosis , and cirrhosis , of which two SPECT parameters , the minimum pixel count for spleen region of interest and maximum pixel count for right hepatic lobe , correctly classified 39 of 46 SPECT/biopsy pairs . In conclusion , this pilot trial identified SPECT parameters that correlated with liver histology changes . A larger study is needed to demonstrate whether SPECT parameters alone or with other markers can provide information on fibrosis with the clinical significance obtained through liver biopsy Background : Chronic hepatitis C in HIV-infected patients is an increasing cause of death dependent on the development of liver fibrosis , which is currently assessed by liver biopsy despite its limitations . Liver stiffness measurement , a new noninvasive method , allows the evaluation of liver fibrosis . The aim of this prospect i ve study was to assess the accuracy of liver stiffness measurement for the detection of fibrosis and cirrhosis in HIV/hepatitis C virus (HCV)-coinfected patients and to compare its accuracy with other noninvasive methods . Methods : We studied 72 consecutive HIV patients with chronic hepatitis C who had a simultaneous liver biopsy and liver stiffness measurement by transient elastography ( FibroScan ; Echosens , Paris , France ) for the assessment of liver fibrosis . Results : Liver stiffness values ranged from 3.0 to 46.4 kilopascal . Liver stiffness was significantly correlated to fibrosis stage ( Kendall τ-b = 0.48 ; P < 0.0001 ) . The area under the receiver operating characteristic ( AUROC ) curve of liver stiffness measurement was 0.72 for F ≥ 2 and 0.97 for F = 4 . For the diagnosis of cirrhosis , AUROC curves of liver stiffness measurement were significantly higher than those for platelet count ( P = 0.02 ) , aspartate aminotransferase (AST)/alanine aminotransferase ( ALT ) ratio ( P = 0.0001 ) , Aspartate aminotransferase-to-Platelet Ratio Index ( APRI ) ( P = 0.01 ) , and FIB-4 ( P = 0.004 ) . Conclusion : Liver stiffness measurement is a promising noninvasive method for the assessment of fibrosis in HIV-infected patients with chronic HCV infection . Its use for the follow-up of these patients should be further evaluated The diagnostic yield of blind percutaneous liver biopsy is improved when two or three specimens are taken during the procedure by redirecting the needle through a single entry-site , without exposing the patient to a greater risk of complications provided that st and ard pre caution s are taken . This study was design ed to obtain further data on the safety of this procedure at King Edward VIII Hospital , Durban . During the period 1984 - 1990 ( inclusive ) a total of 2,646 biopsies were carried out : a single specimen was obtained in 834 patients , two specimens in 983 patients and three in 829 patients . Complications directly attributable to the procedure occurred in 24 patients who had one specimen , 20 who had two , and 19 who had three specimens taken during the biopsy . A single specimen had been obtained from three of the eight patients who had died , two specimens had been taken from another patient , and three specimens were obtained from the other four patients , i.e. patients in whom two or three specimens were taken did not have a higher incidence of pain , symptomatic hypotension , biliary peritonitis or death than those in whom one specimen was taken . Accordingly , when blind percutaneous needle biopsy of the liver is carried out , two specimens should be obtained by redirecting the needle through a single entry site as this improves the diagnostic yield without increasing complications . The morbidity and mortality associated with liver biopsy in this hospital is , however , high . Good technique , careful monitoring of patients after biopsy and prompt and aggressive resuscitation are essential if the mortality rate is to be reduced AIM To assess the correlation between the fibrotic area ( FA ) as calculated by a digital image analysis ( DIA ) , and to compare the diagnostic accuracy of FibroScan to the other existing Liver fibrosis ( LF ) markers using the receiver operating curve analysis . METHODS We recruited 30 patients who underwent a liver resection for three different etiologies including normal liver , hepatitis B , and hepatitis C. Liver stiffness was measured by using a FibroScan . The FA was then calculated by DIA to evaluate LF in order to avoid any sampling bias . RESULTS The FA negatively correlated with Prothrom-bin time ( PT ) , platelet count , lecithin-cholesterol acyltransferase ( LCAT ) , and pre-albumin ( ALB ) . On the other h and , the findings of FibroScan correlated with similar markers . The FA positively correlated with FibroScan , serum hyaluronate level , and type IV collagen level , and aspartate transaminase to platelet ratio index ( APRI ) . The area under the receiver operating curve for FibroScan was higher than that for the other markers , even though the statistical significance was minimal . CONCLUSION Our findings suggest that FibroScan can initially be used to assess LF as an alternative to a liver biopsy ( LB ) and serum diagnosis , because it is a safe method with comparable diagnostic accuracy regarding the existing LF markers The objective was to assess the clinical usefulness of high resolution ultrasound ( US ) analysis of the liver surface for the diagnosis of cirrhosis . In a prospect i ve study , US evaluation of the ventral contour of the liver was performed using a 7.5 MHz linear transducer in 100 patients with suspected liver disease . Only reproducible diffuse ventral liver surface irregularities were considered as an objective US sign of cirrhosis . All patients underwent liver biopsy and /or laparoscopy in order to obtain a definitive diagnosis . Disease prevalence for cirrhosis was 49 % . In nine cases the visualized US irregularities were both unconvincing and hardly reproducible . Consequently , they were considered as non-diagnostic and excluded from further analysis . On 91 diagnostic studies , the sensitivity of US for cirrhosis was 91.1 % , the specificity 93.5 % and the accuracy 92.3 % . Positive and negative predictive values were 93.2 % and 91.5 % , respectively . Provided non-diagnostic cases were considered as technically satisfactory studies and included as true-positive and false-positive cases , this would slightly increase the sensitivity but decrease specificity and accuracy to 91.8 % , 84.3 % , and 88.0 % , respectively . High resolution US analysis of the ventral liver contour is a clinical ly reliable non-invasive test for the diagnosis of cirrhosis Objective To develop and vali date a non-invasive index to predict the presence of cirrhosis in patients with chronic hepatitis C on the basis of clinical , laboratory , and ultrasound findings . Material s and methods Data from the complete history and physical examination , serologic studies , liver ultrasound , and liver biopsy of patients with chronic hepatitis C were analyzed using multivariate regression to develop a cirrhosis predictive index . This index was then applied prospect ively to another group of patients with chronic hepatitis C to determine its accuracy . Results Three hundred and thirty-two patients were included ( mean age , 48.5±18.7 years ; male – female ratio , 1.27 ) . Sixty-seven patients ( 20 % ) had cirrhosis at histology . Logistic regression identified seven variables that predicted cirrhosis : age ≥60 years , platelet count ≤100 ( ×109/L ) , AST/ALT ≥1 , prothrombin time ( Ratio ) ≥1.1 , cau date hypertrophy , right lobe atrophy and splenomegaly . Patients scoring ≥22 in total had a statistically significant probability of cirrhosis ( sensitivity , 80 % ; specificity , 96 % ; and diagnostic accuracy , 94 % ) . Conclusion Cirrhosis can be predicted in patients with chronic hepatitis C by the evaluation of seven clinical , laboratory , and sonographic variables . The index will be useful for the management and follow-up of hepatitis C patients drastically reducing the indications for biopsy in this context BACKGROUND & AIMS Accurate disease staging in chronic hepatitis C ( CHC ) infection helps guide treatment and may provide prognostic information . Liver biopsies are invasive , costly , and associated with morbidity . We hypothesized that a noninvasive test of liver fibrosis can accurately stage liver fibrosis . We prospect ively evaluated the FIBROSpect II ( FSII ) biomarker panel versus pathology assessment and a quantitative measure of fibrosis . METHODS Liver biopsy specimens and serum were obtained from 252 CHC patients , including 50 posttransplant , from 3 tertiary centers . Biopsy specimens were scored central ly and independently at each site , along with central quantification of fibrosis by digitized morphometry . Serum tests were performed blinded to clinical or histologic evaluation . RESULTS The mean biopsy specimen length was 1.95 + /- 0.87 cm ; prevalence of stage F2 through F4 fibrosis was 77 % . Agreement between central and site readings for individual stages was modest ( k = 0.674 ) , with concordant readings in 106 of 248 ( 43 % ) biopsy specimens . The area under the receiver operating characteristic curve for FSII and morphometry for stages F2 through F4 for concordant biopsy specimens were 0.823 and 0.728 , respectively . Sensitivity and specificity for FSII were 83.5 % and 66.7 % , respectively , with an accuracy of 80.2 % . The aspartate aminotransferase to platelet ratio index sensitivity and specificity for predicting F2 through F4 were 30.4 % and 100 % , respectively , the indeterminate rate was 40.4 % , and the accuracy rate was 48.4 % . The accuracy of FSII in concordant biopsy specimens in the posttransplant cohort was 73 % . CONCLUSIONS Serum biomarkers can differentiate mild from moderate-to-severe fibrosis . This prospect i ve study vali date s the performance characteristics of FSII in CHC patients and a posttransplant cohort . Assessing the diagnostic utility of biomarkers is limited by variability in methods to quantify fibrosis and poor interobserver agreement for histologic staging BACKGROUND & AIMS The purpose of our study was to prospect ively compare the success rate and diagnostic accuracy of magnetic resonance elastography , ultrasound elastography , and aspartate aminotransferase to platelets ratio index ( APRI ) measurements for the noninvasive staging of fibrosis in patients with chronic liver disease . METHODS We performed a prospect i ve blind comparison of magnetic resonance elastography , ultrasound elastography , and APRI in a consecutive series of patients who underwent liver biopsy for chronic liver disease in a university-based hospital . Histopathologic staging of liver fibrosis according to the METAVIR scoring system served as the reference . RESULTS A total of 141 patients were assessed . The technical success rate of magnetic resonance elastography was higher than that of ultrasound elastography ( 133/141 [ 94 % ] vs 118/141 [ 84 % ] ; P = .016 ) . Magnetic and ultrasound elastography , APRI measurements , and histopathologic analysis of liver biopsy specimens were technically successful in 96 patients . The areas under the receiver operating characteristic curves of magnetic resonance elasticity ( 0.994 for F > or= 2 ; 0.985 for F > or= 3 ; 0.998 for F = 4 ) were larger ( P < .05 ) than those of ultrasound elasticity , APRI , and the combination of ultrasound elasticity and APRI ( 0.837 , 0.709 , and 0.849 for F > or= 2 ; 0.906 , 0.816 , and 0.936 for F > or= 3 ; 0.930 , 0.820 , and 0.944 for F = 4 , respectively ) . CONCLUSIONS Magnetic resonance elastography has a higher technical success rate than ultrasound elastography and a better diagnostic accuracy than ultrasound elastography and APRI for staging liver fibrosis Although most hepatitis C virus ( HCV ) infections are acquired by injection drug use , prospect i ve data on the progression of liver fibrosis are sparse . Baseline liver biopsies were obtained ( 1996–1998 ) on a r and om sample of 210 out of 1667 HCV‐positive injection drug users ( IDUs ) . Subjects were followed biannually , with a second biopsy offered to those eligible . Paired biopsies were scored 0 to 6 ( modified Ishak score ) , significant fibrosis was defined as score 3 or greater , and progression of fibrosis was defined as an increase 2 or more units or clinical evidence of end‐stage liver disease . Predictive values of blood markers [ FibroSURE , aspartate aminotransferase‐to‐platelet‐ratio index ( APRI ) and alanine aminotransferase ( ALT ) ] were assessed for detection of contemporaneous and future liver fibrosis . Among 119 prospect ively followed IDUs , 96 % were African American ; 97 % HCV genotype 1a/b ; 27 % HIV‐infected , and median age was 42 years . Most ( 90.7 % ) did not have significant liver fibrosis at first biopsy . Although predictive value for detecting insignificant fibrosis at first biopsy was greater than 95 % for FibroSURE , APRI , and ALT , specificities were 88.9 % , 72.7 % , and 72.7 % , respectively . After 4.2 years median follow‐up , 21 % had progression of fibrosis , which was significantly associated with serum level of HCV RNA and ALT . No serological test had predictive value greater than 40 % for contemporaneous or future significant fibrosis . Even initial biopsy result had only a 30.4 % value for predicting future significant fibrosis . In conclusion , significant liver fibrosis and progression were detected in some , but not most , IDUs in this cohort . In this setting with low fibrosis prevalence , FibroSURE , ALT , and APRI tests predict insignificant fibrosis ; however , further work is needed to find noninvasive markers of significant liver fibrosis . ( HEPATOLOGY 2006;43:788–795 . AIM The current study aims to assess the role of the histological parameters in liver biopsy for explaining the variance of liver stiffness , as well as the performance of transient elastography in quantifying liver fibrosis in patients with chronic hepatitis C. METHODS 324 consecutive CHC patients were prospect ively included in this study . All of them had positive HCV-RNA in serum and had underwent percutaneous liver biopsy for grading and staging the diseases ( METAVIR scoring system ) . All were referred to liver stiffness measurement 1 day prior to biopsy . RESULTS Liver stiffness values were strongly correlated with fibrosis ( r=0.759 , p<0.0005 ) . They also correlated with steatosis ( r=0.255 , p<0.0005 ) , necroinflammatory activity ( r=0.378 , p<0.0005 ) and hepatic iron deposition ( r=0.143 , p=0.03 ) . The univariate regression analysis demonstrated that fibrosis ( sq . R=0.610 , p<0.0005 ) , activity ( sq . R=0.145 , p<0.0005 ) and steatosis ( sq . R=0.037 , p=0.002 ) were correlated with liver stiffness . In multiple regression analysis , all three variables independently influenced liver stiffness : fibrosis ( p<0.0005 ) , activity ( p=0.039 ) and steatosis ( p=0.025 ) . Together they explained 62.4 % of the variance of the liver stiffness . The areas under ROC curve for the diagnosis of fibrosis F > or = 1 , F > or = 2 , F > or =3 , and F=4 were 0.936 , 0.862 , 0.910 and 0.938 , for the cut-off values of 4.9 kPa , 7.4 kPa , 9.1 kPa and 11.85 kPa respectively . CONCLUSIONS Transient elastography is a useful method for chronic hepatitis C assessment . Fibrosis is the main predictor of liver stiffness , but activity and steatosis also influence liver stiffness BACKGROUND AND AIMS Transient elastography ( FibroScan ; Echosens , Paris , France ) is a novel , noninvasive , and rapid bedside method to assess liver fibrosis by measuring liver stiffness . We prospect ively assessed the performance of FibroScan in patients with chronic hepatitis C , in comparison with and combined with currently available biochemical markers ( Fibrotest ; Biopredictive ; and the aspartate transaminase to platelets ratio index [ APRI ] ) ; a liver biopsy examination performed the same day served as the reference . METHODS We studied 183 consecutive patients with chronic hepatitis C ( METAVIR fibrosis stage F1 , n = 47 ; F2 , n = 53 ; F3 , n = 37 ; F4 , n = 46 ) . RESULTS FibroScan values ranged from 2.4 to 75.4 kilopascals ( median , 7.4 kilopascals ) . Cut-off values were 7.1 kPa for F > or = 2 , 9.5 kPa for F > or = 3 , and 12.5 kPa for F = 4 . The areas under the receiver operating characteristic ( ROC ) curve of FibroScan , FibroTest , and APRI values were of the same order ( .83 , .85 , and .78 , respectively , for F > or = 2 ; .90 , .90 , and .84 , respectively , for F > or = 3 ; and .95 , .87 , and .83 , respectively , for F = 4 ) . The best performance was obtained by combining the FibroScan and FibroTest , with areas under the ROC curve of .88 for F > or = 2 , .95 for F > or = 3 , and .95 for F = 4 . When the FibroScan and FibroTest results agreed , liver biopsy examination confirmed them in 84 % of cases for F > or = 2 , in 95 % for F > or = 3 , and in 94 % for F = 4 . CONCLUSIONS FibroScan is a simple and effective method for assessing liver fibrosis , with similar performance to FibroTest and APRI . The combined use of FibroScan and FibroTest to evaluate liver fibrosis could avoid a biopsy procedure in most patients with chronic hepatitis AIM To identify a multi serum protein pattern as well as single protein markers using surface-enhanced laser desorption/ionisation time-of-flight mass spectrometry ( SELDI-TOF-MS ) for detection and differentiation of liver fibrosis ( F1-F2 ) , liver cirrhosis ( F4 ) and hepatocellular carcinoma ( HCC ) in patients with chronic hepatitis C virus ( HCV ) . METHODS Serum sample s of 39 patients with F1/F2 fibrosis , 44 patients with F4 fibrosis , 34 patients with HCC were applied to CM10 arrays and analyzed using the SELDI-TOF ProteinChip System ( PBS-IIc ; Ciphergen Biosystems ) after anion-exchange fractionation . All patients had chronic hepatitis C and histologically confirmed fibrosis stage/HCC . Data were analyzed for protein patterns by multivariate statistical techniques and artificial neural networks . RESULTS A 4 peptide/protein multimarker panel ( 7486 , 12,843 , 44,293 and 53,598 Da ) correctly identified HCCs with a sensitivity of 100 % and specificity of 85 % in a two way-comparison of HCV-cirrhosis versus HCV-HCC training sample s ( AUROC 0.943 ) . Sensitivity and specificity for identification of HCC were 68 % and 80 % for r and om test sample s. Cirrhotic patients could be discriminated against patients with F1 or F2 fibrosis using a 5 peptide/protein multimarker pattern ( 2873 , 6646 , 7775 , 10,525 and 67,867 Da ) with a specificity of 100 % and a sensitivity of 85 % in training sample s ( AUROC 0.976 ) and a sensitivity and specificity of 80 % and 67 % for r and om test sample s. Combination of the biomarker classifiers with APRI score and alfa-fetopotein ( AFP ) improved the diagnostic performance . The 6646 Da marker protein for liver fibrosis was identified as apolipoprotein C-I. CONCLUSION SELDI-TOF-MS technology combined with protein pattern analysis seems a valuable approach for the identification of liver cirrhosis and hepatocellular carcinoma in patients with chronic hepatitis C. Most probably a combination of different serum markers will help to identify liver cirrhosis and early-stage hepatocellular carcinomas in the future We constructed noninvasive models to predict significant fibrosis ( F > or = 2 ) and advanced fibrosis ( F > or = 3 ) among human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected patients , naïve for anti-HCV treatment . A total of 296 patients with liver biopsy were r and omly assigned to an estimation group ( EG = 226 ; 70 % ) and a validation group ( VG = 70 ; 30 % ) . We developed the Hospital Gregorio Marañón (HGM)-1 index , based on platelet count , aspartate aminotransferase ( AST ) and glucose , to predict F > or = 2 and the HGM-2 index , based on platelet count , international normalized ratio , alkaline phosphatase and AST to predict F > or = 3 . The area under the receiver operating characteristic curves ( AUROCs ) of the HGM-1 index for the EG and the VG were 0.807 and 0.712 respectively . The AUROCs of the HGM-2 index for the EG and the VG were 0.844 and 0.815 respectively . With the HGM-1 index applied to the VG , using best cutoff scores , the negative predictive value ( NPV ) to exclude F > or = 2 was 54.5 % and the positive predictive value ( PPV ) to confirm F > or = 2 was 93.3 % . With the HGM-2 index applied to the VG , using best cutoff scores , the NPV to exclude F > or = 3 was 92.3 , and the PPV to confirm F > or = 3 was 64.3 % . Thus , HGM-2 accurately predicted F > or = 3 among HIV/HCV-coinfected patients . HGM-1 was less accurate at predicting F > or = 2 BACKGROUND / AIMS In chronic hepatitis C ( CHC ) infection , a liver biopsy provides important information that guides treatment decisions , but is invasive , expensive and associated with possible complications . Extracellular matrix remodeling proteins may be useful non-invasive markers of fibrosis . The aim of this study was to evaluate the diagnostic accuracy of a panel of these markers in CHC patients , develop a predictive algorithm that differentiates no/mild ( METAVIR F0-F1 ) from moderate/severe ( F2-F4 ) fibrosis , and vali date the model in external cohorts . METHODS A combination of matrix markers were initially evaluated and optimized in 294 CHC patients from a single center , and vali date d in an external cohort of 402 patients . RESULTS Hyaluronic acid , TIMP-1 and alpha2-macroglobulin were selected as having the best predictive accuracy for F2-F4 fibrosis ( combined AUROC = 0.831 ) . At an index cut-off > 0.36 and prevalence for F2-F4 of 52 % , results in all 696 patients indicated positive and negative predictive values of 74.3 and 75.8 % with an accuracy of 75 % . CONCLUSIONS The three-marker panel may reliably differentiate CHC patients with moderate/severe fibrosis from those with no/mild fibrosis , although accurate delineation between stages was not possible . Prospect i ve studies are required to determine the potential utility of the marker panel in guiding treatment decisions and following disease progression |
13,813 | 17,943,738 | The evidence provided by the three included RCTs shows that enemas do not have a significant effect on infection rates such as perineal wound infection or other neonatal infections and women 's satisfaction . | BACKGROUND The use of enemas during labour usually reflects the preference of the attending healthcare provider .
However , enemas may cause discomfort for women and increase the costs of delivery .
OBJECTIVES To assess the effects of enemas applied during the first stage of labour on infection rates in mothers and newborns , duration of labour , perineal wound dehiscence in the mother , perineal pain and faecal soiling . | Two hundred and seventy-four women admitted for delivery of singleton infants were studied for the effects of a preparatory enema on faecal contamination , duration of labour , and the incidence of infection in the newborn . Altogether 149 of the women were given an enema ( controls ) and 125 were not . The two groups showed no significant difference in the degree of faecal contamination during the first and second stages of labour , and the incidences of gross contamination were similar . Contamination after an enema was especially difficult to control , since it was more likely to be fluid . Seven neonates in each group showed evidence of infection , bowel organisms being isolated from four in the no-enema group and two in the control group . Duration s of labour , though not strictly comparable , were similar in the two groups . The findings suggest that when preparing for normal labour the enema should be reserved for women who have not had their bowels open in the past 24 hours and have an obviously loaded rectum on initial pelvic examination The effect of a soap enema on the progress of labour was studied in 160 women admitted for delivery in Esigodini District Hospital . The study was set up as a 1:1 r and omised case control study in 200 women . It was changed to a 1:3 case control study after 82 subjects had been studied , when it became apparent that the midwives were no longer willing to follow the study protocol . Forty women received an enema and 120 did not . Two focus group discussion s were held with 16 women who had an enema . The 12 hospital midwives were asked to give their opinion on enemas . Focus group discussion s were also held with 28 traditional midwives . Dilation of the cervix was 2.19 cm/hour in the non-enema group ( 95pc confidence interval 1.86 - 2.52 ) and 2.00 cm/hour in the enema group ( 95pc confidence interval 1.38 - 2.62 ) . The difference is not significant ( t-test : p-value = 0.58 ) . Pregnant women did not like enemas , midwives preferred not to administer them and were not concerned with contamination during delivery . Traditional midwives do not use enemas in labouring women and consider the possible contamination as normal . It is concluded that there is no benefit from routine enemas in labour Abstract Background Enemas are used during labour in obstetric setting s with the belief that they reduce puerperal and neonatal infections , shorten labour duration , and make delivery cleaner for attending personnel . However , a systematic review of the literature found insufficient evidence to support the use of enemas . The objective of this RCT was to address an identified knowledge gap by determining the effect of routine enemas used during the first stage of labour on puerperal and neonatal infection rates . Methods Design : RCT ( r and omised controlled trial ; r and omized clinical trial ) . Outcomes : Clinical diagnosis of maternal or neonatal infections , labour duration , delivery types , episiotomy rates , and prescription of antibiotics Setting : Tertiary care referral hospital at the Javeriana University ( Bogotá , Colombia ) that attended 3170 births during study period with a caesarean section rate of 26 % . Participants : 443 women admitted for delivery to the obstetrics service ( February 1997 to February 1998 ) and followed for a month after delivery . Inclusion criteria were women with : low risk pregnancy and expected to remain in Bogotá during follow up ; gestational age ≥ 36 weeks ; no pelvic or systemic bacterial infection ; intact membranes ; cervix dilatation ≤7 cm . Intervention : 1 litre saline enema , versus no enema , allocated following a block r and om allocation sequence and using sealed opaque envelopes . Results Allocation provided balanced groups and 86 % of the participants were followed up for one month . The overall infection rate for newborns was 21 % , and 18 % for women . We found no significant differences in puerperal or neonatal infection rates ( Puerperal infection : 41/190 [ 22 % ] with enema v 26/182 [ 14 % ] without enema ; RR 0.66 CI 95 % : 0.43 to 1.03 ; neonatal infection 38/191 [ 20 % ] with enema v 40/179 [ 22 % ] without enema ; RR 1.12 , 95 % CI 95 % 0.76 to 1.66 ) , and median labour time was similar between groups ( 515 min . with enema v 585 min . without enema ; P = 0.24 ) . Enemas did n't significantly change episiorraphy dehiscence rates ( 21/182 [ 12 % ] with enema v 32/190 [ 17 % ] without enema ; P = 0.30 ) . Conclusion This RCT found no evidence to support routine use of enemas during labour . Although these results can not rule out a small clinical effect , it seems unlikely that enemas will improve maternal and neonatal outcomes and provide an overall benefit OBJECTIVE To compare the maternal and neonatal outcomes between enema and no-enema in pregnant women on admission in labor . MATERIAL AND METHOD One thous and and one hundred term pregnant women with labor pain were selected r and omly on admission to be assigned into two groups at Rajavithi Hospital from 1 February 2002 to 15 June 2002 . Five -hundred and thirty-nine cases received enema and five-hundred and sixty one cases received noenema . Seventy three women ( 39 and 34 cases from the enema and no-enema groups , respectively ) were excluded because of cesarean section due to obstetric indications . Five hundred cases received enema and five-hundred and twenty -seven cases received no-enema . All cases were delivered vaginally . RESULTS There was no statistical significant difference between the two groups with regards to maternal age , gestational age , gravidity , parity , mode of delivery , type of episiotomy and degree of perineal tear . Fecal contamination rate during the second stage of labor was significantly higher in the women who received no-enema ( 34.9 % ) in comparision with those receiving enema ( 22.8 % ( p < 0.001 ) . No neonatal infection occurred in both groups . Duration of labor was significantly longer in the women who received no-enema ( 459.8 min ) compared with those who received enema ( 409.4 min ) ( p < 0.001 ) . CONCLUSION No-enema methods on admission in labor had significantly more increase infecal contamination in the second stage of labor and longer duration of labor than the enema method But there was no difference in perineal wound infection and neonatal infection between both groups BACKGROUND Intervention rates in maternity practice s vary considerably across Canadian provinces and territories . The objective of this study was to describe the use of routine interventions and practice s in labor and birth as reported by women in the Maternity Experiences Survey of the Canadian Perinatal Surveillance System . Rates of interventions and practice s are considered in the light of current evidence and both Canadian and international recommendations . METHODS A sample of 8,244 estimated eligible women was identified from a r and omly selected sample of recently born infants drawn from the May 2006 Canadian Census and stratified primarily by province and territory . Birth mothers living with their infants at the time of interview were invited to participate in a computer-assisted telephone interview conducted by Statistics Canada on behalf of the Public Health Agency of Canada . Interviews averaged 45 minutes long and were completed when infants were between 5 and 10 months old ( 9 - 14 mo in the territories ) . Completed responses were obtained from 6,421 women ( 78 % ) . RESULTS Women frequently reported electronic fetal monitoring , a health care practitioner starting or speeding up their labor ( or trying to do so ) , epidural anesthesia , episiotomy , and a supine position for birth . Some women also reported pubic or perineal shaves , enemas , and pushing on the top of their abdomen . CONCLUSIONS Several practice s and interventions were commonly reported in labor and birth in Canada , although evidence and Canadian and international guidelines recommend against their routine use . Practice s not recommended for use at all , such as shaving , were also reported While taking an enema to induce labor is a controversial issue worldwide , in Taiwan it remains a routine procedure in many hospitals in preparation for birth . Episiotomy is also a prevalent procedure performed during the birthing process . Some physicians believe that enemas help reduce the risk of feces contamination of the episiotomy incision and , therefore , are justified as a routine procedure . This study compared the neonatal infection rates , times to appearance of fetal head , times to first post-labor bowel movement , and rates of episiotomy dehiscence of women receiving a pre-labor enema against those who did not . A total of 534 women classified with low-risk pregnancies were recruited from a medical center in central Taiwan and assigned r and omly into one of two groups for a six-month period . The first group ( 264 subjects ) received routine enema procedures prior to delivery in the first 6 months . The second group ( 270 subjects ) did not receive enemas . Study results revealed no significant difference between enema and non-enema groups in terms of infection rates in mothers or infants or in terms of average time to fetal head appearance . While labor duration was the same for the two groups in the first and third stages of labor , the enema group experienced a relatively shorter second stage . No significant difference was observed in times to first post-labor bowel movement or episiotomy dehiscence rates . The results of this study indicate that the administration of enemas as a routine practice prior to labor is not substantiated by medical necessity . However , limitations of the research design suggest that a r and omized clinical trial be adopted in the future to explore further the scientific validity of study results |
13,814 | 27,096,326 | Subgroup analyses by disease setting revealed improvements in all outcomes , whereas for therapy setting , an improved benefit for bortezomib was observed in all outcomes and subgroups except for OS following consolidation therapy .
This meta- analysis found that myeloma patients receiving bortezomib benefited in terms of OS , PFS and response rate compared to those who did not receive bortezomib .
This benefit was observed in trials of bortezomib versus no bortezomib with the same background therapy and in trials of bortezomib versus no bortezomib with different background therapy in each arm or compared to other agent(s ) . | BACKGROUND Multiple myeloma is a malignancy of plasma cells accounting for approximately 1 % of cancers and 12 % of haematological malignancies .
The first-in-class proteasome inhibitor , bortezomib , is commonly used to treat newly diagnosed as well as relapsed/refractory myeloma , either as single agent or combined with other therapies .
OBJECTIVES We conducted a systematic review and meta- analysis to assess the effects of bortezomib on overall survival ( OS ) , progression-free survival ( PFS ) , response rate ( RR ) , health-related quality of life ( HRQoL ) , adverse events ( AEs ) and treatment-related death ( TRD ) . | The phase III MMY-3021 study compared safety and efficacy of subcutaneous versus intravenous administration of the proteasome inhibitor bortezomib in patients with relapsed myeloma . The initial report demonstrated non-inferior efficacy with subcutaneous versus intravenous bortezomib for the primary end point : overall response rate after four cycles of single-agent bortezomib . We report up date d outcome analyses after prolonged follow up . Best response rate ( after up to ten cycles of bortezomib ± dexamethasone ) remained 52 % in each arm , including 23 % and 22 % complete or near-complete responses with subcutaneous and intravenous bortezomib , respectively . Time to progression ( median 9.7 vs. 9.6 months ; hazard ratio 0.872 , P=0.462 ) , progression-free survival ( median 9.3 vs. 8.4 months ; hazard ratio 0.846 , P=0.319 ) , and overall survival ( 1-year : 76.4 % vs. 78.0 % , P=0.788 ) were comparable with subcutaneous versus intravenous bortezomib . Peripheral neuropathy rates remained significantly lower with subcutaneous versus intravenous bortezomib , with increased rates of improvement/resolution at the time of this analysis BACKGROUND Thalidomide plus dexamethasone ( TD ) is a st and ard induction therapy for myeloma . We aim ed to assess the efficacy and safety of addition of bortezomib to TD ( VTD ) versus TD alone as induction therapy before , and consolidation therapy after , double autologous stem-cell transplantation in newly diagnosed multiple myeloma . METHODS Patients ( aged 18 - 65 years ) with previously untreated symptomatic myeloma were enrolled from 73 sites in Italy between May , 2006 , and April , 2008 , and data collection continued until June 30 , 2010 . Patients were r and omly allocated ( 1:1 ratio ) by a web-based system to receive three 21-day cycles of thalidomide ( 100 mg daily for the first 14 days and 200 mg daily thereafter ) plus dexamethasone ( 40 mg daily on 8 of the first 12 days , but not consecutively ; total of 320 mg per cycle ) , either alone or with bortezomib ( 1·3 mg/m(2 ) on days 1 , 4 , 8 , and 11 ) . The r and omisation sequence was computer generated by the study coordinating team and was stratified by disease stage . After double autologous stem-cell transplantation , patients received two 35-day cycles of their assigned drug regimen , VTD or TD , as consolidation therapy . The primary endpoint was the rate of complete or near complete response to induction therapy . Analysis was by intention to treat . Patients and treating physicians were not masked to treatment allocation . This study is still underway but is not recruiting participants , and is registered with Clinical Trials.gov , number NCT01134484 , and with EudraCT , number 2005 - 003723 - 39 . FINDINGS 480 patients were enrolled and r and omly assigned to receive VTD ( n=241 patients ) or TD ( n=239 ) . Six patients withdrew consent before start of treatment , and 236 on VTD and 238 on TD were included in the intention-to-treat analysis . After induction therapy , complete or near complete response was achieved in 73 patients ( 31 % , 95 % CI 25·0 - 36·8 ) receiving VTD , and 27 ( 11 % , 7·3 - 15·4 ) on TD ( p<0·0001 ) . Grade 3 or 4 adverse events were recorded in a significantly higher number of patients on VTD ( n=132 , 56 % ) than in those on TD ( n=79 , 33 % ; p<0·0001 ) , with a higher occurrence of peripheral neuropathy in patients on VTD ( n=23 , 10 % ) than in those on TD ( n=5 , 2 % ; p=0·0004 ) . Resolution or improvement of severe peripheral neuropathy was recorded in 18 of 23 patients on VTD , and in three of five patients on TD . INTERPRETATION VTD induction therapy before double autologous stem-cell transplantation significantly improves rate of complete or near complete response , and represents a new st and ard of care for patients with multiple myeloma who are eligible for transplant . FUNDING Seràgnoli Institute of Haematology at the University of Bologna , Bologna , Italy The phase 3 VISTA study ( Clinical Trials.gov NCT00111319 ) in transplant‐ineligible myeloma patients demonstrated superior efficacy with bortezomib‐melphalan‐prednisone ( VMP ; nine 6‐wk cycles ) vs. melphalan‐prednisone ( MP ) but also increased toxicity . Health‐related quality of life ( HRQoL ; exploratory endpoint ) was evaluated using the European Organization for Research and Treatment of Cancer ( EORTC ) Quality of Life Question naire ( QLQ‐C30 ) Combinations of bortezomib ( V ) and dexamethasone ( D ) with either lenalidomide ( R ) or cyclophosphamide ( C ) have shown significant efficacy . This r and omized phase 2 trial evaluated VDC , VDR , and VDCR in previously untreated multiple myeloma ( MM ) . Patients received V 1.3 mg/m2 ( days 1 , 4 , 8 , 11 ) and D 40 mg ( days 1 , 8 , 15 ) , with either C 500 mg/m2 ( days 1 , 8) and R 15 mg ( days 1 - 14 ; VDCR ) , R 25 mg ( days 1 - 14 ; VDR ) , C 500 mg/m2 ( days 1 , 8 ; VDC ) or C 500 mg/m2 ( days 1 , 8 , 15 ; VDC-mod ) in 3-week cycles ( maximum 8 cycles ) , followed by maintenance with V 1.3 mg/m2 ( days 1 , 8 , 15 , 22 ) for four 6-week cycles ( all arms)≥very good partial response was seen in 58 % , 51 % , 41 % , and 53 % ( complete response rate of 25 % , 24 % , 22 % , and 47 % ) of patients ( VDCR , VDR , VCD , and VCD-mod , respectively ) ; the corresponding 1-year progression-free survival was 86 % , 83 % , 93 % , and 100 % , respectively . Common adverse events included hematologic toxicities , peripheral neuropathy , fatigue , and gastrointestinal disturbances . All regimens were highly active and well tolerated in previously untreated MM , and , based on this trial , VDR and VCD-mod are preferred for clinical practice and further comparative testing . No substantial advantage was noted with VDCR over the 3-drug combinations . This trial is registered at www . clinical trials.gov ( NCT00507442 ) In a r and omized , phase 3 study , superior complete/near-complete response ( CR/nCR ) rates and extended progression-free survival were demonstrated with bortezomib-thalidomide-dexamethasone ( VTD ) versus thalidomide-dexamethasone ( TD ) as induction therapy before , and consolidation after , double autologous stem cell transplantation for newly diagnosed myeloma patients ( intention-to-treat analysis ; VTD , n = 236 ; TD , n = 238 ) . This per- protocol analysis ( VTD , n = 160 ; TD , n = 161 ) specifically assessed the efficacy and safety of consolidation with VTD or TD . Before starting consolidation , CR/nCR rates were not significantly different in the VTD ( 63.1 % ) and TD arms ( 54.7 % ) . After consolidation , CR ( 60.6 % vs 46.6 % ) and CR/nCR ( 73.1 % vs 60.9 % ) rates were significantly higher for VTD-treated versus TD-treated patients . VTD consolidation significantly increased CR and CR/nCR rates , but TD did not ( McNemar test ) . With a median follow-up of 30.4 months from start of consolidation , 3-year progression-free survival was significantly longer for the VTD group ( 60 % vs 48 % for TD ) . Grade 2 or 3 peripheral neuropathy ( 8.1 % vs 2.4 % ) was more frequent with VTD ( grade 3 , 0.6 % ) versus TD consolidation . The superior efficacy of VTD versus TD as induction was retained despite readministration as consolidation therapy after double autologous transplantation . VTD consolidation therapy significantly contributed to improved clinical outcomes observed for patients r and omly assigned to the VTD arm of the study . The study is registered at www . clinical trials.gov as # NCT01134484 The Intergroupe Francophone du Myelome conducted a r and omized trial to compare bortezomib-dexamethasone ( VD ) as induction before high-dose therapy ( HDT ) and autologous stem cell transplantation ( ASCT ) to a combination consisting of reduced doses of bortezomib and thalidomide plus dexamethasone ( vtD ) in patients with multiple myeloma . Overall , a total of 199 patients were central ly r and omly assigned to receive VD or vtD. After 4 cycles , the complete response ( CR ) rate was the same in both groups ( 13 % in the vtD arm , 12 % in the VD arm , P = .74 ) . However , the CR plus very good partial response ( VGPR ) rate was significantly higher in the vtD arm ( 49 % vs 36 % , P = .05 ) . After ASCT , the CR plus VGPR rate was significantly higher in the vtD arm ( 74 % vs 58 % , P = .02 ) . The reduced doses of bortezomib and thalidomide translated into a reduced incidence of peripheral neuropathy ( PN ) : grade ≥ 2 PN were reported in 34 % in the VD arm versus 14 % in the vtD arm ( P = .001 ) . vtD , including reduced doses of bortezomib and thalidomide , yields higher VGPR rates compared with VD and can be considered a new effective triplet combination before HDT/ASCT Initial analysis of the Assessment of Proteasome Inhibition for Extending Remissions ( APEX ) trial of relapsed multiple myeloma patients showed significantly longer time to progression , higher response rate , and improved survival with single-agent bortezomib versus high-dose dexamethasone . In this up date d analysis ( median follow-up : 22 months ) , survival was assessed in both arms , and efficacy up date d for the bortezomib arm . Median survival was 29.8 months for bortezomib versus 23.7 months for dexamethasone , a 6-month benefit , despite substantial crossover from dexamethasone to bortezomib . Overall and complete response rates with bortezomib were 43 % and 9 % , respectively ; among responding patients , 56 % improved response with longer therapy beyond initial response , leading to continued improvement in overall quality of response . Higher response quality ( 100 % M-protein reduction ) was associated with longer response duration ; response duration was not associated with time to response . These data confirm the activity of bortezomib and support extended treatment in relapsed multiple myeloma patients tolerating therapy The Nordic Myeloma Study Group conducted an open r and omized trial to compare bortezomib as consolidation therapy given after high-dose therapy and autologous stem cell transplantation ( ASCT ) with no consolidation in bortezomib-naive patients with newly diagnosed multiple myeloma . Overall , 370 patients were central ly r and omly assigned 3 months after ASCT to receive 20 doses of bortezomib given during 21 weeks or no consolidation . The hypothesis was that consolidation therapy would prolong progression-free survival ( PFS ) . The PFS after r and omization was 27 months for the bortezomib group compared with 20 months for the control group ( P = .05 ) . Fifty-one of 90 patients in the treatment group compared with 32 of 90 controls improved their response after r and omization ( P = .007 ) . No difference in overall survival was seen . Fatigue was reported more commonly by the bortezomib-treated patients in self-reported quality -of-life ( QOL ) question naires , whereas no other major differences in QOL were recorded between the groups . Consolidation therapy seemed to be beneficial for patients not achieving at least a very good partial response ( VGPR ) but not for patients in the ≥ VGPR category at r and omization . Consolidation with bortezomib after ASCT in bortezomib-naive patients improves PFS without interfering with QOL . This trial was registered at www . clinical trials.gov as # NCT00417911 Objectives Thalidomide and bortezomib have been frequently used for second-line therapy in patients with myeloma relapsing after or refractory to initial melphalan-based treatment , but no r and omized trials have been published comparing these two treatment alternatives . Methods Thalidomide- and bortezomib-naïve patients with melphalan refractory myeloma were r and omly assigned to low-dose thalidomide + dexamethasone ( Thal-Dex ) or bortezomib + dexamethasone ( Bort-Dex ) . At progression on either therapy , the patients were offered crossover to the alternative drug combination . An estimated 300 patients would be needed for the trial to detect a 50 % difference in median PFS between the treatment arms . Results After inclusion of 131 patients , the trial was prematurely closed because of low accrual . Sixty-seven patients were r and omized to Thal-Dex and 64 to Bort-Dex . Progression-free survival was similar ( median , 9.0 months for Thal-Dex and 7.2 for Bort-Dex ) . Response rate was similar ( 55 % for Thal-Dex and 63 % for Bort-Dex ) , but time to response was shorter ( P < 0.05 ) and the VGPR rate higher ( P < 0.01 ) for Bort-Dex . Time-to-other treatment after crossover was similar ( median , 13.2 months for Thal-Dex and 11.2 months for Bort-Dex ) , as was overall survival ( 22.8 months for Thal-Dex and 19.0 for Bort-Dex ) . Venous thromboembolism was seen in seven patients and cerebrovascular events in four patients in the Thal-Dex group . Severe neuropathy , reactivation of herpes virus infections , and mental depression were more frequently observed in the Bort-Dex group . In the quality -of-life analysis , no difference was noted for physical function , pain , and global quality of life . Fatigue and sleep disturbances were significantly more prevalent in the Bort-Dex group . Conclusions Thalidomide ( 50–100 mg daily ) in combination with dexamethasone seems to have an efficacy comparable with that of bortezomib and dexamethasone in melphalan refractory myeloma . However , the statistical strength of the results in this study is limited by the low number of included patients The Spanish Myeloma Group conducted a trial to compare bortezomib/thalidomide/dexamethasone ( VTD ) versus thalidomide/dexamethasone ( TD ) versus vincristine , BCNU , melphalan , cyclophosphamide , prednisone/vincristine , BCNU , doxorubicin , dexamethasone/bortezomib ( V BMC P/VBAD/B ) in patients aged 65 years or younger with multiple myeloma . The primary endpoint was complete response ( CR ) rate postinduction and post-autologous stem cell transplantation ( ASCT ) . Three hundred eighty-six patients were allocated to VTD ( 130 ) , TD ( 127 ) , or V BMC P/VBAD/B ( 129 ) . The CR rate was significantly higher with VTD than with TD ( 35 % vs 14 % , P = .001 ) or with V BMC P/VBAD/B ( 35 % vs 21 % , P = .01 ) . The median progression-free survival ( PFS ) was significantly longer with VTD ( 56.2 vs 28.2 vs 35.5 months , P = .01 ) . In an intention-to-treat analysis , the post-ASCT CR rate was higher with VTD than with TD ( 46 % vs 24 % , P = .004 ) or with V BMC P/VBAD/B ( 46 % vs 38 % , P = .1 ) . Patients with high-risk cytogenetics had a shorter PFS and overall survival in the overall series and in all treatment groups . In conclusion , VTD result ed in a higher pre- and posttransplantation CR rate and in a significantly longer PFS although it was not able to overcome the poor prognosis of high-risk cytogenetics . Our results support the use of VTD as a highly effective induction regimen prior to ASCT . The study was registered with http://www . clinical trials.gov ( NCT00461747 ) and Eudra CT ( no. 2005 - 001110 - 41 ) Health‐related quality of life ( HRQL ) was prospect ively measured during the phase III APEX trial of bortezomib versus dexamethasone in relapsed multiple myeloma patients . The European Organisation for Research and Treatment of Cancer ( EORTC ) Quality of Life Question naire – Core ( QLQ‐C30 ) and Functional Assessment of Cancer Therapy/Gynecologic Oncology Group – Neurotoxicity ( NTX ) side‐effects question naires were administered at baseline and every 6 weeks up to 42 weeks . Patients receiving bortezomib ( 1·3 mg/m2 , days 1 , 4 , 8 and 11 for eight 3‐week cycles , then days 1 , 8 , 15 and 22 for three 5‐week cycles ; n = 296 ) demonstrated significantly better mean Global Health Status over the study versus patients receiving dexamethasone ( 40 mg/d , days 1–4 , 9–12 , and 17–20 for four 5‐week cycles , then days 1–4 only for five 4‐week cycles ; n = 302 ) , plus significantly better physical health , role , cognitive , and emotional functioning scores , lower dyspnoea and sleep symptom scores , and better NTX question naire score , using multiple imputation to account for missing data . Results were similar using available‐ data analyses . Sensitivity analyses suggested that improved HRQL with bortezomib is at least partially explained by improved survival . These results show that bortezomib was associated with significantly better multidimensional HRQL compared with dexamethasone , consistent with the better clinical outcomes seen with bortezomib Multiple myeloma , a plasma cell neoplasm , is the second most common hematologic malignancy after non-Hodgkins lymphoma and is responsible for 2 % of cancer deaths . Melphalan and prednisone ( MP ) has been the st and ard treatment in elderly patients for many decades . The VISTA study evaluated the effect of this combination with or without the first-in-class proteasome inhibitor bortezomib in newly diagnosed myeloma patients who were not c and i date s for autologous stem cell transplantation . Altogether 682 patients were enrolled and prospect ively r and omized in this trial . All patients received nine 6-week cycles of oral melphalan ( 9 mg/m(2 ) ) and prednisone ( 60 mg/m(2 ) ) on days 1 - 4 , either alone or with bortezomib administered intravenously ( 1.3 mg/m(2 ) on days 1 , 4 , 8 , 11 , 22 , 25 , 29 and 32 during the first four cycles and on days 1 , 8 , 22 , 29 during remaining course of therapy ) . Median time to progression ( the primary end point of the trial ) was 24 months in the bortezomib-containing group compared with 16.6 months in the control group ( p < 0.001 ) . Response was evaluated in 337 patients receiving bortezomib compared with 331 patients in the control group who received MP alone ; the percentages of partial response or better was 71 vs 35 % ( p < 0.001 ) , with complete response seen in 30 vs 4 % , respectively ( p < 0.001 ) . Median response duration in both groups was 19.9 versus 13.1 months , respectively . Median overall survival has not been reached in VMP group compared with 43 months in the MP group ( p < 0.001 ) , and this benefit is maintained after long term follow-up and subsequent antimyeloma therapies . Hematological adverse events ( AEs ) were similar in both groups , although patients in the bortezomib group experienced more frequent peripheral sensory neuropathy ( including 13 % grade 3 , with less than 1 % grade 4 ) . Overall , the occurrence of grade 3 AEs was higher in patients receiving bortezomib ( 53 vs 44 % , p = 0.02 ) , but the risk of grade 4 AEs was identical ( 28 vs 27 % ) . These results confirm the superiority of MP plus bortezomib combination over MP therapy in treatment-naive patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplantation PURPOSE Bortezomib-melphalan-prednisone ( VMP ) has improved overall survival in multiple myeloma . This r and omized trial compared VMP plus thalidomide ( VMPT ) induction followed by bortezomib-thalidomide maintenance ( VMPT-VT ) with VMP in patients with newly diagnosed multiple myeloma . PATIENTS AND METHODS We r and omly assigned 511 patients who were not eligible for transplantation to receive VMPT-VT ( nine 5-week cycles of VMPT followed by 2 years of VT maintenance ) or VMP ( nine 5-week cycles without maintenance ) . RESULTS In the initial analysis with a median follow-up of 23 months , VMPT-VT improved complete response rate from 24 % to 38 % and 3-year progression-free-survival ( PFS ) from 41 % to 56 % compared with VMP . In this analysis , median follow-up was 54 months . The median PFS was significantly longer with VMPT-VT ( 35.3 months ) than with VMP ( 24.8 months ; hazard ratio [ HR ] , 0.58 ; P < .001 ) . The time to next therapy was 46.6 months in the VMPT-VT group and 27.8 months in the VMP group ( HR , 0.52 ; P < .001 ) . The 5-year overall survival ( OS ) was greater with VMPT-VT ( 61 % ) than with VMP ( 51 % ; HR , 0.70 ; P = .01 ) . Survival from relapse was identical in both groups ( HR , 0.92 ; P = .63 ) . In the VMPT-VT group , the most frequent grade 3 to 4 adverse events included neutropenia ( 38 % ) , thrombocytopenia ( 22 % ) , peripheral neuropathy ( 11 % ) , and cardiologic events ( 11 % ) . All of these , except for thrombocytopenia , were significantly more frequent in the VMPT-VT patients . CONCLUSION Bortezomib and thalidomide significantly improved OS in multiple myeloma patients not eligible for transplantation BACKGROUND This study compared bortezomib with high-dose dexamethasone in patients with relapsed multiple myeloma who had received one to three previous therapies . METHODS We r and omly assigned 669 patients with relapsed myeloma to receive either an intravenous bolus of bortezomib ( 1.3 mg per square meter of body-surface area ) on days 1 , 4 , 8 , and 11 for eight three-week cycles , followed by treatment on days 1 , 8 , 15 , and 22 for three five-week cycles , or high-dose dexamethasone ( 40 mg orally ) on days 1 through 4 , 9 through 12 , and 17 through 20 for four five-week cycles , followed by treatment on days 1 through 4 for five four-week cycles . Patients who were assigned to receive dexamethasone were permitted to cross over to receive bortezomib in a companion study after disease progression . RESULTS Patients treated with bortezomib had higher response rates , a longer time to progression ( the primary end point ) , and a longer survival than patients treated with dexamethasone . The combined complete and partial response rates were 38 percent for bortezomib and 18 percent for dexamethasone ( P<0.001 ) , and the complete response rates were 6 percent and less than 1 percent , respectively ( P<0.001 ) . Median times to progression in the bortezomib and dexamethasone groups were 6.22 months ( 189 days ) and 3.49 months ( 106 days ) , respectively ( hazard ratio , 0.55 ; P<0.001 ) . The one-year survival rate was 80 percent among patients taking bortezomib and 66 percent among patients taking dexamethasone ( P=0.003 ) , and the hazard ratio for overall survival with bortezomib was 0.57 ( P=0.001 ) . Grade 3 or 4 adverse events were reported in 75 percent of patients treated with bortezomib and in 60 percent of those treated with dexamethasone . CONCLUSIONS Bortezomib is superior to high-dose dexamethasone for the treatment of patients with multiple myeloma who have had a relapse after one to three previous therapies PURPOSE To compare efficacy and safety of bortezomib plus dexamethasone and vincristine plus doxorubicin plus dexamethasone ( VAD ) as induction before stem-cell transplantation in previously untreated myeloma . PATIENTS AND METHODS Four hundred eighty-two patients were r and omly assigned to VAD ( n = 121 ) , VAD plus dexamethasone , cyclophosphamide , etoposide , and cisplatin ( DCEP ) consolidation ( n = 121 ) , bortezomib plus dexamethasone ( n = 121 ) , or bortezomib plus dexamethasone plus DCEP ( n = 119 ) , followed by autologous stem-cell transplantation . Patients not achieving very good partial response ( VGPR ) required a second transplantation . The primary end point was postinduction complete response/near complete response ( CR/nCR ) rate . RESULTS Postinduction CR/nCR ( 14.8 % v 6.4 % ) , at least VGPR ( 37.7 % v 15.1 % ) , and overall response ( 78.5 % v 62.8 % ) rates were significantly higher with bortezomib plus dexamethasone versus VAD ; CR/nCR and at least VGPR rates were higher regardless of disease stage or adverse cytogenetic abnormalities . Response rates were similar in patients who did and did not receive DCEP . Post first transplantation , CR/nCR ( 35.0 % v 18.4 % ) and at least VGPR ( 54.3 % v 37.2 % ) rates remained significantly higher with bortezomib plus dexamethasone . Median progression-free survival ( PFS ) was 36.0 months versus 29.7 months ( P = .064 ) with bortezomib plus dexamethasone versus VAD ; respective 3-year survival rates were 81.4 % and 77.4 % ( median follow-up , 32.2 months ) . The incidence of severe adverse events appeared similar between groups , but hematologic toxicity and deaths related to toxicity ( zero v seven ) were more frequent with VAD . Conversely , rates of grade 2 ( 20.5 % v 10.5 % ) and grade s 3 to 4 ( 9.2 % v 2.5 % ) peripheral neuropathy during induction through first transplantation were significantly higher with bortezomib plus dexamethasone . CONCLUSION Bortezomib plus dexamethasone significantly improved postinduction and post-transplantation CR/nCR and at least VGPR rates compared with VAD and result ed in a trend for longer PFS . Bortezomib plus dexamethasone should therefore be considered a st and ard of care in this setting This r and omized , retrospective study evaluated the effect of thalidomide combined with bortezomib-dexamethasone ( TBD ) or vincristine-doxorubicin-dexamethasone ( T-VAD ) on 46 patients with multiple myeloma . Newly diagnosed patients were r and omly allocated to receive TBD ( n = 24 ) or T-VAD ( n = 22 ) . The high- quality response rate ( complete response plus very good partial response ) was 62.5 % in the TBD group and 45.4 % for T-VAD . The complete response rate was 29.2 % for TBD and 13.6 % for T-VAD . Overall survival at 2 and 3 years , respectively , was 91.7 % and 62.5 % for TBD versus 86.4 % and 54.5 % for T-VAD . Most of the toxic effects of treatment were well tolerated . Both regimens were effective in the treatment of newly diagnosed multiple myeloma patients . Further studies are required to determine the role of thalidomide in these two regimens BACKGROUND Bortezomib plus melphalan and prednisone ( VMP ) is significantly better than melphalan plus prednisone alone for elderly patients with untreated multiple myeloma ; however , toxic effects are high . We investigated a novel and less intensive bortezomib-based regimen to maintain efficacy and to reduce toxic effects . METHODS Between March , 2006 , and October , 2008 , 260 patients with untreated multiple myeloma , 65 years and older , from 63 Spanish centres , were r and omly assigned to receive six cycles of VMP ( n=130 ) or bortezomib plus thalidomide and prednisone ( VTP ; n=130 ) as induction therapy , consisting of one cycle of bortezomib twice per week for 6 weeks ( 1·3 mg/m² on days 1 , 4 , 8 , 11 , 22 , 25 , 29 , and 32 ) , plus either melphalan ( 9 mg/m² on days 1 - 4 ) or daily thalidomide ( 100 mg ) , and prednisone ( 60 mg/m² on days 1 - 4 ) . The first cycle was followed by five cycles of bortezomib once per week for 5 weeks ( 1·3 mg/m² on days 1 , 8 , 15 , and 22 ) plus the same doses of melphalan plus prednisone and thalidomide plus prednisone . 178 patients completed the six induction cycles and were r and omly assigned to maintenance therapy with bortezomib plus prednisone ( n=87 ) or bortezomib plus thalidomide ( n=91 ) , consisting of one conventional cycle of bortezomib for 3 weeks ( 1·3 mg/m² on days 1 , 4 , 8 , and 11 ) every 3 months , plus either prednisone ( 50 mg every other day ) or thalidomide ( 50 mg per day ) , for up to 3 years . Treatment codes were generated with a computerised r and om number generator , and neither participants nor study personnel were masked to treatment . The primary endpoint was response rate in induction and maintenance phases . Analysis was by intention to treat . This trial is registered with Clinical Trials.gov , number NCT00443235 . FINDINGS In the induction phase , 105 ( 81 % ) patients in the VTP group and 104 ( 80 % ) in the VMP group achieved partial responses or better ( p=0·9 ) , including 36 ( 28 % ) and 26 ( 20 % ) complete remissions , respectively ( p=0·2 ) . Treatment with VTP result ed in more serious adverse events ( 40 [ 31 % ] vs 20 [ 15 % ] , p=0·01 ) and discontinuations ( 22 [ 17 % ] vs 15 [ 12 % ] , p=0·03 ) than did treatment with VMP . The most common toxicities ( grade 3 or worse ) were infections ( one [ 1 % ] in the VTP group vs nine [ 7 % ] in the VMP group ) , cardiac events ( 11 [ 8 % ] vs 0 ) , and peripheral neuropathy ( nine [ 7 % ] vs 12 [ 9 % ] ) . After maintenance therapy , the complete remission rate was 42 % ( 40 [ 44 % ] patients in complete remission in the bortezomib plus thalidomide group , 34 [ 39 % ] in the bortezomib plus prednisone group ) . No grade 3 or worse haematological toxicities were recorded during maintenance therapy ; two ( 2 % ) patients in the bortezomib plus prednisone group and six ( 7 % ) in the bortezomib plus thalidomide group developed peripheral neuropathy . INTERPRETATION Reduced-intensity induction with a bortezomib-based regimen , followed by maintenance , is a safe and effective treatment for elderly patients with multiple myeloma . FUNDING Pethema ( Spanish Program for the Treatment of Hematologic Diseases ) PURPOSE The combination of bortezomib-melphalan-prednisone ( VMP ) is a new st and ard of care for newly diagnosed multiple myeloma . This phase III study examined the efficacy of the four-drug combination of bortezomib-melphalan-prednisone-thalidomide ( VMPT ) followed by maintenance with bortezomib-thalidomide ( VMPT-VT ) compared with VMP treatment alone in untreated multiple myeloma patients who are ineligible for autologous stem-cell transplantation . PATIENTS AND METHODS A total of 511 patients were r and omly assigned to receive nine cycles of VMPT followed by continuous VT as maintenance , or nine cycles of VMP at the same doses with no additional therapy . The primary end point was progression-free survival . RESULTS The 3-year estimates of progression-free survival were 56 % in patients receiving VMPT-VT and 41 % in those receiving VMP ( hazard ratio [ HR ] , 0.67 ; 95 % CI , 0.50 to 0.90 ; P = .008 ) . At 3 years , the cumulative proportions of patients who did not go on to the next therapy were 72 % with VMPT-VT and 60 % with VMP ( HR , 0.58 ; 95 % CI , 0.50 to 0.90 ; P = .007 ) . Complete response rates were 38 % in the VMPT-VT group and 24 % in the VMP group ( P < .001 ) . The 3-year overall survival was 89 % with VMPT-VT and 87 % with VMP ( HR , 0.92 ; 95 % CI , 0.53 to 1.60 ; P = .77 ) . Grade 3 to 4 neutropenia ( 38 % v 28 % ; P = .02 ) , cardiologic events ( 10 % v 5 % ; P = .04 ) , and thromboembolic events ( 5 % v 2 % ; P = .08 ) were more frequent among patients assigned to the VMPT-VT group than among those assigned to the VMP group ; treatment-related deaths were 4 % with VMPT-VT and 3 % with VMP . CONCLUSION VMPT followed by VT as maintenance was superior to VMP alone in patients with multiple myeloma who are ineligible for autologous stem-cell transplantation BACKGROUND Bortezomib , a boronic acid dipeptide , is a novel proteasome inhibitor that has been shown in pre clinical and phase 1 studies to have antimyeloma activity . METHODS In this multicenter , open-label , nonr and omized , phase 2 trial , we enrolled 202 patients with relapsed myeloma that was refractory to the therapy they had received most recently . Patients received 1.3 mg of bortezomib per square meter of body-surface area twice weekly for 2 weeks , followed by 1 week without treatment , for up to eight cycles ( 24 weeks ) . In patients with a suboptimal response , oral dexamethasone ( 20 mg daily , on the day of and the day after bortezomib administration ) was added to the regimen . The response was evaluated according to the criteria of the European Group for Blood and Marrow Transplantation and confirmed by an independent review committee . RESULTS Of 193 patients who could be evaluated , 92 percent had been treated with three or more of the major classes of agents for myeloma , and in 91 percent , the myeloma was refractory to the therapy received most recently . The rate of response to bortezomib was 35 percent , and those with a response included 7 patients in whom myeloma protein became undetectable and 12 in whom myeloma protein was detectable only by immunofixation . The median overall survival was 16 months , with a median duration of response of 12 months . Grade 3 adverse events included thrombocytopenia ( in 28 percent of patients ) , fatigue ( in 12 percent ) , peripheral neuropathy ( in 12 percent ) , and neutropenia ( in 11 percent ) . Grade 4 events occurred in 14 percent of patients . CONCLUSIONS Bortezomib , a member of a new class of anticancer drugs , is active in patients with relapsed multiple myeloma that is refractory to conventional chemotherapy In a phase 2 open‐label study of the novel proteasome inhibitor bortezomib , 54 patients with multiple myeloma who had relapsed after or were refractory to frontline therapy were r and omized to receive intravenous 1·0 or 1·3 mg/m2 bortezomib twice weekly for 2 weeks , every 3 weeks for a maximum of eight cycles . Dexamethasone was permitted in patients with progressive or stable disease after two or four cycles respectively . Responses were determined using modified European Group for Blood and Marrow Transplantation criteria . The complete response ( CR ) + partial response ( PR ) rate for bortezomib alone was 30 % [ 90 % confidence interval ( CI ) , 15·7–47·1 ] and 38 % ( 90 % CI , 22·6–56·4 ) in the 1·0 mg/m2 ( 8 of 27 patients ) and 1·3 mg/m2 ( 10 of 26 patients ) groups respectively . The CR + PR rate for patients who received bortezomib alone or in combination with dexamethasone was 37 % and 50 % for the 1·0 and 1·3 mg/m2 cohorts respectively . The most common grade 3 adverse events were thrombocytopenia ( 24 % ) , neutropenia ( 17 % ) , lymphopenia ( 11 % ) and peripheral neuropathy ( 9 % ) . Grade 4 events were observed in 9 % ( five of 54 patients ) . Bortezomib alone or in combination with dexamethasone demonstrated therapeutic activity in patients with multiple myeloma who relapsed after frontline therapy BACKGROUND Intravenous injection is the st and ard administration route of bortezomib ; however , subcutaneous administration is an important alternative . We compared the efficacy and safety of subcutaneous versus intravenous bortezomib at the approved 1·3 mg/m(2 ) dose and twice per week schedule in patients with relapsed multiple myeloma . METHODS This r and omised , phase 3 study was undertaken at 53 centres in ten countries in Europe , Asia , and South America . Patients aged 18 years and older with relapsed multiple myeloma after one to three previous lines of therapy were r and omly assigned to receive up to eight 21-day cycles of bortezomib 1·3 mg/m(2 ) , on days 1 , 4 , 8 , and 11 , by subcutaneous injection or intravenous infusion . R and omisation was by an interactive voice response system based on a computer-generated r and omisation schedule , stratified by number of previous lines and disease stage . Patients and treating physicians were not masked to treatment allocation . The primary objective was to show non-inferiority of subcutaneous versus intravenous bortezomib in terms of overall response rate ( ORR ) after four cycles in all patients with a diagnosis of measurable , secretory multiple myeloma who received one or more dose of drug ( response-evaluable population ) . Non-inferiority was defined as retaining 60 % of the intravenous treatment effect . This study is registered with Clinical Trials.gov , number NCT00722566 , and is ongoing for long-term follow-up . FINDINGS 222 patients were r and omly assigned to receive subcutaneous ( n=148 ) or intravenous ( n=74 ) bortezomib . The response-evaluable population consisted of 145 patients in the subcutaneous group and 73 in the intravenous group . Patients received a median of eight cycles ( range one to ten ) in both groups . ORR after four cycles was 42 % in both groups ( 61 patients in subcutaneous group and 31 in intravenous group ; ORR difference -0·4 % , 95 % CI -14·3 to 13·5 ) , showing non-inferiority ( p=0·002 ) . After a median follow-up of 11·8 months ( IQR 7·9 - 16·8 ) in the subcutaneous group and 12·0 months ( 8·1 - 15·6 ) in the intravenous group , there were no significant differences in time to progression ( median 10·4 months , 95 % CI 8·5 - 11·7 , vs 9·4 months , 7·6 - 10·6 ; p=0·387 ) and 1-year overall survival ( 72·6 % , 95 % CI 63·1 - 80·0 , vs 76·7 % , 64·1 - 85·4 ; p=0·504 ) with subcutaneous versus intravenous bortezomib . Grade 3 or worse adverse events were reported in 84 ( 57 % ) patients in the subcutaneous group versus 52 ( 70 % ) in the intravenous group ; the most common were thrombocytopenia ( 19 [ 13 % ] vs 14 [ 19 % ] ) , neutropenia ( 26 [ 18 % ] vs 13 [ 18 % ] ) , and anaemia ( 18 [ 12 % ] vs six [ 8 % ] ) . Peripheral neuropathy of any grade ( 56 [ 38 % ] vs 39 [ 53 % ] ; p=0·044 ) , grade 2 or worse ( 35 [ 24 % ] vs 30 [ 41 % ] ; p=0·012 ) , and grade 3 or worse ( nine [ 6 % ] vs 12 [ 16 % ] ; p=0·026 ) was significantly less common with subcutaneous than with intravenous administration . Subcutaneous administration was locally well tolerated . INTERPRETATION Subcutaneous bortezomib offers non-inferior efficacy to st and ard intravenous administration , with an improved safety profile . FUNDING Johnson & Johnson Pharmaceutical Research and Development , and Millennium Pharmaceuticals PURPOSE This phase III international study compared the efficacy and safety of a combination of pegylated liposomal doxorubicin ( PLD ) plus bortezomib with bortezomib monotherapy in patients with relapsed or refractory multiple myeloma . PATIENTS AND METHODS Six hundred forty-six patients were r and omly assigned to receive either intravenous bortezomib 1.3 mg/m(2 ) on days 1 , 4 , 8 , and 11 of an every 21-days cycle , or the same bortezomib regimen with PLD 30 mg/m(2 ) on day 4 . RESULTS Median time to progression was increased from 6.5 months for bortezomib to 9.3 months with the PLD + bortezomib combination ( P = .000004 ; hazard ratio , 1.82 [ monotherapy v combination therapy ] ; 95 % CI , 1.41 to 2.35 ) . The 15-month survival rate for PLD + bortezomib was 76 % compared with 65 % for bortezomib alone ( P = .03 ) . The complete plus partial response rate was 41 % for bortezomib and 44 % for PLD + bortezomib , a difference that was not statistically significant . Median duration of response was increased from 7.0 to 10.2 months ( P = .0008 ) with PLD + bortezomib . Grade 3/4 adverse events were more frequent in the combination group ( 80 % v 64 % ) , with safety profiles consistent with the known toxicities of the two agents . An increased incidence in the combination group was seen of grade 3/4 neutropenia , thrombocytopenia , asthenia , fatigue , diarrhea , and h and -foot syndrome . CONCLUSION PLD with bortezomib is superior to bortezomib monotherapy for the treatment of patients with relapsed or refractory multiple myeloma . The combination therapy is associated with a higher incidence of grade 3/4 myelosuppression , constitutional symptoms , and GI and dermatologic toxicities PURPOSE The purpose of this study was to confirm overall survival ( OS ) and other clinical benefits with bortezomib , melphalan , and prednisone ( VMP ) versus melphalan and prednisone ( MP ) in the phase III VISTA ( Velcade as Initial St and ard Therapy in Multiple Myeloma ) trial after prolonged follow-up , and evaluate the impact of subsequent therapies . PATIENTS AND METHODS Previously untreated symptomatic patients with myeloma ineligible for high-dose therapy received up to nine 6-week cycles of VMP ( n = 344 ) or MP ( n = 338 ) . RESULTS With a median follow-up of 36.7 months , there was a 35 % reduced risk of death with VMP versus MP ( hazard ratio , 0.653 ; P < .001 ) ; median OS was not reached with VMP versus 43 months with MP ; 3-year OS rates were 68.5 % versus 54.0 % . Response rates to subsequent thalidomide- ( 41 % v 53 % ) and lenalidomide-based therapies ( 59 % v 52 % ) appeared similar after VMP or MP ; response rates to subsequent bortezomib-based therapy were 47 % versus 59 % . Among patients treated with VMP ( n = 178 ) and MP ( n = 233 ) , median survival from start of subsequent therapy was 30.2 and 21.9 months , respectively , and there was no difference in survival from salvage among patients who received subsequent bortezomib , thalidomide , or lenalidomide . Rates of adverse events were higher with VMP versus MP during cycles 1 to 4 , but similar during cycles 5 to 9 . With VMP , 79 % of peripheral neuropathy events improved within a median of 1.9 months ; 60 % completely resolved within a median of 5.7 months . CONCLUSION VMP significantly prolongs OS versus MP after lengthy follow-up and extensive subsequent antimyeloma therapy . First-line bortezomib use does not induce more resistant relapse . VMP used upfront appears more beneficial than first treating with conventional agents and saving bortezomib- and other novel agent-based treatment until relapse The Clinical Response and Efficacy Study of Bortezomib in the Treatment of Relapsing Multiple Myeloma ( CREST ) demonstrated substantial activity with two dose levels of bortezomib ( 1·0 and 1·3 mg/m2 ) , alone or with dexamethasone , in relapsed or refractory multiple myeloma . We present up date d survival analyses after prolonged follow‐up ( median > 5 years ) . One‐ and 5‐year survival rates were 82 % and 32 % , respectively , in the 1·0 mg/m2 group ( n = 28 ) , and 81 % and 45 % , respectively , in the 1·3 mg/m2 group ( n = 26 ) . Notable survival , response , and time‐to‐progression data suggest that a bortezomib starting dose of 1·3 mg/m2 is preferred . If bortezomib dose reduction is required , the 1·0 mg/m2 dose still offers patients a substantial survival benefit BACKGROUND The st and ard treatment for patients with multiple myeloma who are not c and i date s for high-dose therapy is melphalan and prednisone . This phase 3 study compared the use of melphalan and prednisone with or without bortezomib in previously untreated patients with multiple myeloma who were ineligible for high-dose therapy . METHODS We r and omly assigned 682 patients to receive nine 6-week cycles of melphalan ( at a dose of 9 mg per square meter of body-surface area ) and prednisone ( at a dose of 60 mg per square meter ) on days 1 to 4 , either alone or with bortezomib ( at a dose of 1.3 mg per square meter ) on days 1 , 4 , 8 , 11 , 22 , 25 , 29 , and 32 during cycles 1 to 4 and on days 1 , 8 , 22 , and 29 during cycles 5 to 9 . The primary end point was the time to disease progression . RESULTS The time to progression among patients receiving bortezomib plus melphalan-prednisone ( bortezomib group ) was 24.0 months , as compared with 16.6 months among those receiving melphalan-prednisone alone ( control group ) ( hazard ratio for the bortezomib group , 0.48 ; P<0.001 ) . The proportions of patients with a partial response or better were 71 % in the bortezomib group and 35 % in the control group ; complete-response rates were 30 % and 4 % , respectively ( P<0.001 ) . The median duration of the response was 19.9 months in the bortezomib group and 13.1 months in the control group . The hazard ratio for overall survival was 0.61 for the bortezomib group ( P=0.008 ) . Adverse events were consistent with established profiles of toxic events associated with bortezomib and melphalan-prednisone . Grade 3 events occurred in a higher proportion of patients in the bortezomib group than in the control group ( 53 % vs. 44 % , P=0.02 ) , but there were no significant differences in grade 4 events ( 28 % and 27 % , respectively ) or treatment-related deaths ( 1 % and 2 % ) . CONCLUSIONS Bortezomib plus melphalan-prednisone was superior to melphalan-prednisone alone in patients with newly diagnosed myeloma who were ineligible for high-dose therapy . ( Clinical Trials.gov number , NCT00111319 . Bortezomib is active for newly diagnosed and relapsed multiple myeloma , and it has synergistic activity with melphalan . The authors of this report conducted a r and omized trial to determine the safety and efficacy of adding bortezomib to a preparative regimen of arsenic trioxide ( ATO ) , ascorbic acid ( AA ) , and melphalan Carfilzomib is a next-generation , selective proteasome inhibitor being evaluated for the treatment of relapsed and refractory multiple myeloma . In this open-label , single-arm phase 2 study ( PX-171 - 003-A1 ) , patients received single-agent carfilzomib 20 mg/m(2 ) intravenously twice weekly for 3 of 4 weeks in cycle 1 , then 27 mg/m(2 ) for ≤ 12 cycles . The primary endpoint was overall response rate ( ≥ partial response ) . Secondary endpoints included clinical benefit response rate ( ≥ minimal response ) , duration of response , progression-free survival , overall survival , and safety . A total of 266 patients were evaluable for safety , 257 for efficacy ; 95 % were refractory to their last therapy ; 80 % were refractory or intolerant to both bortezomib and lenalidomide . Patients had median of 5 prior lines of therapy , including bortezomib , lenalidomide , and thalidomide . Overall response rate was 23.7 % with median duration of response of 7.8 months . Median overall survival was 15.6 months . Adverse events ( AEs ) were manageable without cumulative toxicities . Common AEs were fatigue ( 49 % ) , anemia ( 46 % ) , nausea ( 45 % ) , and thrombocytopenia ( 39 % ) . Thirty-three patients ( 12.4 % ) experienced peripheral neuropathy , primarily grade s 1 or 2 . Thirty-three patients ( 12.4 % ) withdrew because of an AE . Durable responses and an acceptable tolerability profile in this heavily pretreated population demonstrate the potential of carfilzomib to offer meaningful clinical benefit . This trial was registered at www . clinical trials.gov as # NCT00511238 PURPOSE The aim of this subset analysis was to determine if bortezomib treatment is associated with increased incidence of varicella-zoster virus ( VZV ) reactivation in patients with relapsed multiple myeloma ( MM ) . PATIENTS AND METHODS Incidence of herpes zoster was evaluated in 663 patients with relapsed MM from the phase III APEX trial comparing single-agent bortezomib with high-dose dexamethasone . RESULTS Bortezomib was associated with a significantly higher incidence of herpes zoster compared with dexamethasone treatment ( 13 % , 42 of 331 v 5 % , 15 of 332 ; P = .0002 ) . Most herpes zoster infections were grade 1/2 ; incidences of grade 3/4 events ( 1.8 % v 1.5 % ) and infections considered serious adverse events ( 1.5 % v 0.9 % ) were similar between treatment arms , and no herpes zoster-related deaths occurred . Neither the time to onset of the herpes event nor the patients ' absolute lymphocyte counts at baseline differed significantly between arms . VZV reactivation was the only herpes viral event noted to be significantly elevated in the bortezomib treatment group compared with the dexamethasone treatment group ( P = .0002 ) . The incidence of non-VZV-related herpes viral infections was comparable between arms . No additional risk factors for herpes zoster reactivation were identified . CONCLUSION Further studies are needed to explain these observations and their implication s ; however , for patients treated with bortezomib or bortezomib-containing regimens , the risk of VZV reactivation should be monitored and routine use of antiviral prophylaxis considered PURPOSE This prospect i ve multicenter phase III study compared the efficacy and safety of a triple combination ( bortezomib-thalidomide-dexamethasone [ VTD ] ) versus a dual combination ( thalidomide-dexamethasone [ TD ] ) in patients with multiple myeloma ( MM ) progressing or relapsing after autologous stem-cell transplantation ( ASCT ) . PATIENTS AND METHODS Overall , 269 patients were r and omly assigned to receive bortezomib ( 1.3 mg/m(2 ) intravenous bolus ) or no bortezomib for 1 year , in combination with thalidomide ( 200 mg per day orally ) and dexamethasone ( 40 mg orally once a day on 4 days once every 3 weeks ) . Bortezomib was administered on days 1 , 4 , 8 , and 11 with a 10-day rest period ( day 12 to day 21 ) for eight cycles ( 6 months ) , and then on days 1 , 8 , 15 , and 22 with a 20-day rest period ( day 23 to day 42 ) for four cycles ( 6 months ) . RESULTS Median time to progression ( primary end point ) was significantly longer with VTD than TD ( 19.5 v13.8 months ; hazard ratio , 0.59 ; 95 % CI , 0.44 to 0.80 ; P = .001 ) , the complete response plus near-complete response rate was higher ( 45 % v 21 % ; P 0.001 ) , and the median duration of response was longer ( 17.9 v 13.4 months ; P.04 ) [corrected].The 24-month survival rate was in favor of VTD ( 71 % v 65 % ; P = .093 ) . Grade 3 peripheral neuropathy was more frequent with VTD ( 29 % v 12 % ; P = .001 ) as were the rates of grade s 3 and 4 infection and thrombocytopenia . CONCLUSION VTD was more effective than TD in the treatment of patients with MM with progressive or relapsing disease post-ASCT but was associated with a higher incidence of grade 3 neurotoxicity PURPOSE We investigated whether bortezomib during induction and maintenance improves survival in newly diagnosed multiple myeloma ( MM ) . PATIENTS AND METHODS In all , 827 eligible patients with newly diagnosed symptomatic MM were r and omly assigned to receive induction therapy with vincristine , doxorubicin , and dexamethasone ( VAD ) or bortezomib , doxorubicin , and dexamethasone ( PAD ) followed by high-dose melphalan and autologous stem-cell transplantation . Maintenance consisted of thalidomide 50 mg ( VAD ) once per day or bortezomib 1.3 mg/m(2 ) ( PAD ) once every 2 weeks for 2 years . The primary analysis was progression-free survival ( PFS ) adjusted for International Staging System ( ISS ) stage . RESULTS Complete response ( CR ) , including near CR , was superior after PAD induction ( 15 % v 31 % ; P < .001 ) and bortezomib maintenance ( 34 % v 49 % ; P < .001 ) . After a median follow-up of 41 months , PFS was superior in the PAD arm ( median of 28 months v 35 months ; hazard ratio [ HR ] , 0.75 ; 95 % CI , 0.62 to 0.90 ; P = .002 ) . In multivariate analysis , overall survival ( OS ) was better in the PAD arm ( HR , 0.77 ; 95 % CI , 0.60 to 1.00 ; P = .049 ) . In high-risk patients presenting with increased creatinine more than 2 mg/dL , bortezomib significantly improved PFS from a median of 13 months to 30 months ( HR , 0.45 ; 95 % CI , 0.26 to 0.78 ; P = .004 ) and OS from a median of 21 months to 54 months ( HR , 0.33 ; 95 % CI , 0.16 to 0.65 ; P < .001 ) . A benefit was also observed in patients with deletion 17p13 ( median PFS , 12 v 22 months ; HR , 0.47 ; 95 % CI , 0.26 to 0.86 ; P = .01 ; median OS , 24 months v not reached at 54 months ; HR , 0.36 ; 95 % CI , 0.18 to 0.74 ; P = .003 ) . CONCLUSION Bortezomib during induction and maintenance improves CR and achieves superior PFS and OS |
13,815 | 31,335,350 | Conclusions : Stratified meta- analysis demonstrates that smoking status is not significantly associated with the response to IO in the treatment of advanced solid organ malignancies | Objectives : Smoking is associated with an increased tumor mutational burden .
As tumor mutational burden has been shown to correlate with response to immunotherapy ( IO ) , we hypothesized that a history of smoking may be associated with better response to IO . | Purpose Patients with squamous non-small-cell lung cancer ( NSCLC ) have poor prognosis and limited treatment options . This r and omized , double-blind , phase III study investigated the efficacy and safety of first-line ipilimumab or placebo plus paclitaxel and carboplatin in advanced squamous NSCLC . Patients and Methods Patients with stage IV or recurrent chemotherapy-naïve squamous NSCLC were r and omly assigned ( 1:1 ) to receive paclitaxel and carboplatin plus blinded ipilimumab 10 mg/kg or placebo every 3 weeks on a phased induction schedule comprising six chemotherapy cycles , with ipilimumab or placebo from cycles 3 to 6 and then , after induction treatment , ipilimumab or placebo maintenance every 12 weeks for patients with stable disease or better . The primary end point was overall survival ( OS ) in patients receiving at least one dose of blinded study therapy . Results Of 956 r and omly assigned patients , 749 received at least one dose of blinded study therapy ( chemotherapy plus ipilimumab , n = 388 ; chemotherapy plus placebo , n = 361 ) . Median OS was 13.4 months for chemotherapy plus ipilimumab and 12.4 months for chemotherapy plus placebo ( hazard ratio , 0.91 ; 95 % CI , 0.77 to 1.07 ; P = .25 ) . Median progression-free survival was 5.6 months for both groups ( hazard ratio , 0.87 ; 95 % CI , 0.75 to 1.01 ) . Rates of grade 3 or 4 treatment-related adverse events ( TRAEs ) , any- grade serious TRAEs , and TRAEs leading to discontinuation were numerically higher with chemotherapy plus ipilimumab ( 51 % , 33 % , and 28 % , respectively ) than with chemotherapy plus placebo ( 35 % , 10 % , and 7 % , respectively ) . Seven treatment-related deaths occurred with chemotherapy plus ipilimumab , and one occurred with chemotherapy plus placebo . Conclusion The addition of ipilimumab to first-line chemotherapy did not prolong OS compared with chemotherapy alone in patients with advanced squamous NSCLC . The safety profile of chemotherapy plus ipilimumab was consistent with that observed in previous lung and melanoma studies . Ongoing studies are evaluating ipilimumab in combination with nivolumab in this population BACKGROUND Atezolizumab is a humanised antiprogrammed death-lig and 1 ( PD-L1 ) monoclonal antibody that inhibits PD-L1 and programmed death-1 ( PD-1 ) and PD-L1 and B7 - 1 interactions , reinvigorating anticancer immunity . We assessed its efficacy and safety versus docetaxel in previously treated patients with non-small-cell lung cancer . METHODS We did a r and omised , open-label , phase 3 trial ( OAK ) in 194 academic or community oncology centres in 31 countries . We enrolled patients who had squamous or non-squamous non-small-cell lung cancer , were 18 years or older , had measurable disease per Response Evaluation Criteria in Solid Tumors , and had an Eastern Cooperative Oncology Group performance status of 0 or 1 . Patients had received one to two previous cytotoxic chemotherapy regimens ( one or more platinum based combination therapies ) for stage IIIB or IV non-small-cell lung cancer . Patients with a history of autoimmune disease and those who had received previous treatments with docetaxel , CD137 agonists , anti-CTLA4 , or therapies targeting the PD-L1 and PD-1 pathway were excluded . Patients were r and omly assigned ( 1:1 ) to intravenously receive either atezolizumab 1200 mg or docetaxel 75 mg/m2 every 3 weeks by permuted block r and omisation ( block size of eight ) via an interactive voice or web response system . Co primary endpoints were overall survival in the intention-to-treat ( ITT ) and PD-L1-expression population TC1/2/3 or IC1/2/3 ( ≥1 % PD-L1 on tumour cells or tumour-infiltrating immune cells ) . The primary efficacy analysis was done in the first 850 of 1225 enrolled patients . This study is registered with Clinical Trials.gov , number NCT02008227 . FINDINGS Between March 11 , 2014 , and April 29 , 2015 , 1225 patients were recruited . In the primary population , 425 patients were r and omly assigned to receive atezolizumab and 425 patients were assigned to receive docetaxel . Overall survival was significantly longer with atezolizumab in the ITT and PD-L1-expression population s. In the ITT population , overall survival was improved with atezolizumab compared with docetaxel ( median overall survival was 13·8 months [ 95 % CI 11·8 - 15·7 ] vs 9·6 months [ 8·6 - 11·2 ] ; hazard ratio [ HR ] 0·73 [ 95 % CI 0·62 - 0·87 ] , p=0·0003 ) . Overall survival in the TC1/2/3 or IC1/2/3 population was improved with atezolizumab ( n=241 ) compared with docetaxel ( n=222 ; median overall survival was 15·7 months [ 95 % CI 12·6 - 18·0 ] with atezolizumab vs 10·3 months [ 8·8 - 12·0 ] with docetaxel ; HR 0·74 [ 95 % CI 0·58 - 0·93 ] ; p=0·0102 ) . Patients in the PD-L1 low or undetectable subgroup ( TC0 and IC0 ) also had improved survival with atezolizumab ( median overall survival 12·6 months vs 8·9 months ; HR 0·75 [ 95 % CI 0·59 - 0·96 ] ) . Overall survival improvement was similar in patients with squamous ( HR 0·73 [ 95 % CI 0·54 - 0·98 ] ; n=112 in the atezolizumab group and n=110 in the docetaxel group ) or non-squamous ( 0·73 [ 0·60 - 0·89 ] ; n=313 and n=315 ) histology . Fewer patients had treatment-related grade 3 or 4 adverse events with atezolizumab ( 90 [ 15 % ] of 609 patients ) versus docetaxel ( 247 [ 43 % ] of 578 patients ) . One treatment-related death from a respiratory tract infection was reported in the docetaxel group . INTERPRETATION To our knowledge , OAK is the first r and omised phase 3 study to report results of a PD-L1-targeted therapy , with atezolizumab treatment result ing in a clinical ly relevant improvement of overall survival versus docetaxel in previously treated non-small-cell lung cancer , regardless of PD-L1 expression or histology , with a favourable safety profile . FUNDING F. Hoffmann-La Roche Ltd , Genentech , BACKGROUND Nivolumab plus ipilimumab showed promising efficacy for the treatment of non – small‐cell lung cancer ( NSCLC ) in a phase 1 trial , and tumor mutational burden has emerged as a potential biomarker of benefit . In this part of an open‐label , multipart , phase 3 trial , we examined progression‐free survival with nivolumab plus ipilimumab versus chemotherapy among patients with a high tumor mutational burden ( ≥10 mutations per megabase ) . METHODS We enrolled patients with stage IV or recurrent NSCLC that was not previously treated with chemotherapy . Those with a level of tumor programmed death lig and 1 ( PD‐L1 ) expression of at least 1 % were r and omly assigned , in a 1:1:1 ratio , to receive nivolumab plus ipilimumab , nivolumab monotherapy , or chemotherapy ; those with a tumor PD‐L1 expression level of less than 1 % were r and omly assigned , in a 1:1:1 ratio , to receive nivolumab plus ipilimumab , nivolumab plus chemotherapy , or chemotherapy . Tumor mutational burden was determined by the FoundationOne CDx assay . RESULTS Progression‐free survival among patients with a high tumor mutational burden was significantly longer with nivolumab plus ipilimumab than with chemotherapy . The 1‐year progression‐free survival rate was 42.6 % with nivolumab plus ipilimumab versus 13.2 % with chemotherapy , and the median progression‐free survival was 7.2 months ( 95 % confidence interval [ CI ] , 5.5 to 13.2 ) versus 5.5 months ( 95 % CI , 4.4 to 5.8 ) ( hazard ratio for disease progression or death , 0.58 ; 97.5 % CI , 0.41 to 0.81 ; P<0.001 ) . The objective response rate was 45.3 % with nivolumab plus ipilimumab and 26.9 % with chemotherapy . The benefit of nivolumab plus ipilimumab over chemotherapy was broadly consistent within subgroups , including patients with a PD‐L1 expression level of at least 1 % and those with a level of less than 1 % . The rate of grade 3 or 4 treatment‐related adverse events was 31.2 % with nivolumab plus ipilimumab and 36.1 % with chemotherapy . CONCLUSIONS Progression‐free survival was significantly longer with first‐line nivolumab plus ipilimumab than with chemotherapy among patients with NSCLC and a high tumor mutational burden , irrespective of PD‐L1 expression level . The results vali date the benefit of nivolumab plus ipilimumab in NSCLC and the role of tumor mutational burden as a biomarker for patient selection . ( Funded by Bristol‐Myers Squibb and Ono Pharmaceutical ; CheckMate 227 Clinical Trials.gov number , NCT02477826 . BACKGROUND Nivolumab , a fully human IgG4 programmed death 1 ( PD-1 ) immune-checkpoint-inhibitor antibody , disrupts PD-1-mediated signaling and may restore antitumor immunity . METHODS In this r and omized , open-label , international phase 3 study , we assigned patients with nonsquamous non-small-cell lung cancer ( NSCLC ) that had progressed during or after platinum-based doublet chemotherapy to receive nivolumab at a dose of 3 mg per kilogram of body weight every 2 weeks or docetaxel at a dose of 75 mg per square meter of body-surface area every 3 weeks . The primary end point was overall survival . RESULTS Overall survival was longer with nivolumab than with docetaxel . The median overall survival was 12.2 months ( 95 % confidence interval [ CI ] , 9.7 to 15.0 ) among 292 patients in the nivolumab group and 9.4 months ( 95 % CI , 8.1 to 10.7 ) among 290 patients in the docetaxel group ( hazard ratio for death , 0.73 ; 96 % CI , 0.59 to 0.89 ; P=0.002 ) . At 1 year , the overall survival rate was 51 % ( 95 % CI , 45 to 56 ) with nivolumab versus 39 % ( 95 % CI , 33 to 45 ) with docetaxel . With additional follow-up , the overall survival rate at 18 months was 39 % ( 95 % CI , 34 to 45 ) with nivolumab versus 23 % ( 95 % CI , 19 to 28 ) with docetaxel . The response rate was 19 % with nivolumab versus 12 % with docetaxel ( P=0.02 ) . Although progression-free survival did not favor nivolumab over docetaxel ( median , 2.3 months and 4.2 months , respectively ) , the rate of progression-free survival at 1 year was higher with nivolumab than with docetaxel ( 19 % and 8 % , respectively ) . Nivolumab was associated with even greater efficacy than docetaxel across all end points in subgroups defined according to prespecified levels of tumor-membrane expression ( ≥1 % , ≥5 % , and ≥10 % ) of the PD-1 lig and . Treatment-related adverse events of grade 3 or 4 were reported in 10 % of the patients in the nivolumab group , as compared with 54 % of those in the docetaxel group . CONCLUSIONS Among patients with advanced nonsquamous NSCLC that had progressed during or after platinum-based chemotherapy , overall survival was longer with nivolumab than with docetaxel . ( Funded by Bristol-Myers Squibb ; CheckMate 057 Clinical Trials.gov number , NCT01673867 . ) Purpose Patients with extensive-stage disease small-cell lung cancer ( SCLC ) have poor survival outcomes despite first-line chemotherapy with etoposide and platinum . This r and omized , double-blind phase III study evaluated the efficacy and safety of ipilimumab or placebo plus etoposide and platinum in patients with newly diagnosed extensive-stage disease SCLC . Patients and Methods Patients were r and omly assigned at a ratio of one to one to receive chemotherapy with etoposide and platinum ( cisplatin or carboplatin ) plus ipilimumab 10 mg/kg or placebo every 3 weeks for a total of four doses each in a phased induction schedule ( chemotherapy in cycles one to four ; ipilimumab or placebo beginning in cycle three up to cycle six ) , followed by ipilimumab or placebo maintenance every 12 weeks . Primary end point was overall survival ( OS ) among patients receiving at least one dose of blinded study therapy . Results Of 1,132 patients r and omly assigned , 954 received at least one dose of study therapy ( chemotherapy plus ipilimumab , n = 478 ; chemotherapy plus placebo , n = 476 ) . Median OS was 11.0 months for chemotherapy plus ipilimumab versus 10.9 months for chemotherapy plus placebo ( hazard ratio , 0.94 ; 95 % CI , 0.81 to 1.09 ; P = .3775 ) . Median progression-free survival was 4.6 months for chemotherapy plus ipilimumab versus 4.4 months for chemotherapy plus placebo ( hazard ratio , 0.85 ; 95 % CI , 0.75 to 0.97 ) . Rates and severity of treatment-related adverse events were similar between arms , except for diarrhea , rash , and colitis , which were more frequent with chemotherapy plus ipilimumab . Rate of treatment-related discontinuation was higher with chemotherapy plus ipilimumab ( 18 % v 2 % with chemotherapy plus placebo ) . Five treatment-related deaths occurred with chemotherapy plus ipilimumab and two with chemotherapy plus placebo . Conclusion Addition of ipilimumab to chemotherapy did not prolong OS versus chemotherapy alone in patients with newly diagnosed extensive-stage disease SCLC . No new or unexpected adverse events were observed with chemotherapy plus ipilimumab . Several ongoing studies are evaluating ipilimumab in combination with programmed death-1 inhibitors in SCLC BACKGROUND Antibodies targeting the immune checkpoint molecules PD-1 or PD-L1 have demonstrated clinical efficacy in patients with metastatic non-small-cell lung cancer ( NSCLC ) . In this trial we investigated the efficacy and safety of avelumab , an anti-PD-L1 antibody , in patients with NSCLC who had already received platinum-based therapy . METHODS JAVELIN Lung 200 was a multicentre , open-label , r and omised , phase 3 trial at 173 hospitals and cancer treatment centres in 31 countries . Eligible patients were aged 18 years or older and had stage IIIB or IV or recurrent NSCLC and disease progression after treatment with a platinum-containing doublet , an Eastern Cooperative Oncology Group performance status score of 0 or 1 , an estimated life expectancy of more than 12 weeks , and adequate haematological , renal , and hepatic function . Participants were r and omly assigned ( 1:1 ) , via an interactive voice-response system with a stratified permuted block method with variable block length , to receive either avelumab 10 mg/kg every 2 weeks or docetaxel 75 mg/m2 every 3 weeks . R and omisation was stratified by PD-L1 expression ( ≥1 % vs < 1 % of tumour cells ) , which was measured with the 73 - 10 assay , and histology ( squamous vs non-squamous ) . The primary endpoint was overall survival , analysed when roughly 337 events ( deaths ) had occurred in the PD-L1-positive population . Efficacy was analysed in all PD-L1-positive patients ( ie , PD-L1 expression in ≥1 % of tumour cells ) r and omly assigned to study treatment ( the primary analysis population ) and then in all r and omly assigned patients through a hierarchical testing procedure . Safety was analysed in all patients who received at least one dose of study treatment . This trial is registered with Clinical Trials.gov , number NCT02395172 . Enrolment is complete , but the trial is ongoing . FINDINGS Between March 24 , 2015 , and Jan 23 , 2017 , 792 patients were enrolled and r and omly assigned to receive avelumab ( n=396 ) or docetaxel ( n=396 ) . 264 participants in the avelumab group and 265 in the docetaxel group had PD-L1-positive tumours . In patients with PD-L1-positive tumours , median overall survival did not differ significantly between the avelumab and docetaxel groups ( 11·4 months [ 95 % CI 9·4 - 13·9 ] vs 10·3 months [ 8·5 - 13·0 ] ; hazard ratio 0·90 [ 96 % CI 0·72 - 1·12 ] ; one-sided p=0·16 ) . Treatment-related adverse events occurred in 251 ( 64 % ) of 393 avelumab-treated patients and 313 ( 86 % ) of 365 docetaxel-treated patients , including grade 3 - 5 events in 39 ( 10 % ) and 180 ( 49 % ) patients , respectively . The most common grade 3 - 5 treatment-related adverse events were infusion-related reaction ( six patients [ 2 % ] ) and increased lipase ( four [ 1 % ] ) in the avelumab group and neutropenia ( 51 [ 14 % ] ) , febrile neutropenia ( 37 [ 10 % ] ) , and decreased neutrophil counts ( 36 [ 10 % ] ) in the docetaxel group . Serious treatment-related adverse events occurred in 34 ( 9 % ) patients in the avelumab group and 75 ( 21 % ) in the docetaxel group . Treatment-related deaths occurred in four ( 1 % ) participants in the avelumab group , two due to interstitial lung disease , one due to acute kidney injury , and one due to a combination of autoimmune myocarditis , acute cardiac failure , and respiratory failure . Treatment-related deaths occurred in 14 ( 4 % ) patients in the docetaxel group , three due to pneumonia , and one each due to febrile neutropenia , septic shock , febrile neutropenia with septic shock , acute respiratory failure , cardiovascular insufficiency , renal impairment , leucopenia with mucosal inflammation and pyrexia , infection , neutropenic infection , dehydration , and unknown causes . INTERPRETATION Compared with docetaxel , avelumab did not improve overall survival in patients with platinum-treated PD-L1-positive NSCLC , but had a favourable safety profile . FUNDING Merck and Pfizer BACKGROUND An earlier analysis in this phase 3 trial showed that durvalumab significantly prolonged progression‐free survival , as compared with placebo , among patients with stage III , unresectable non – small‐cell lung cancer ( NSCLC ) who did not have disease progression after concurrent chemoradiotherapy . Here we report the results for the second primary end point of overall survival . METHODS We r and omly assigned patients , in a 2:1 ratio , to receive durvalumab intravenously , at a dose of 10 mg per kilogram of body weight , or matching placebo every 2 weeks for up to 12 months . R and omization occurred 1 to 42 days after the patients had received chemoradiotherapy and was stratified according to age , sex , and smoking history . The primary end points were progression‐free survival ( as assessed by blinded independent central review ) and overall survival . Secondary end points included the time to death or distant metastasis , the time to second progression , and safety . RESULTS Of the 713 patients who underwent r and omization , 709 received the assigned intervention ( 473 patients received durvalumab and 236 received placebo ) . As of March 22 , 2018 , the median follow‐up was 25.2 months . The 24‐month overall survival rate was 66.3 % ( 95 % confidence interval [ CI ] , 61.7 to 70.4 ) in the durvalumab group , as compared with 55.6 % ( 95 % CI , 48.9 to 61.8 ) in the placebo group ( two‐sided P=0.005 ) . Durvalumab significantly prolonged overall survival , as compared with placebo ( stratified hazard ratio for death , 0.68 ; 99.73 % CI , 0.47 to 0.997 ; P=0.0025 ) . Up date d analyses regarding progression‐free survival were similar to those previously reported , with a median duration of 17.2 months in the durvalumab group and 5.6 months in the placebo group ( stratified hazard ratio for disease progression or death , 0.51 ; 95 % CI , 0.41 to 0.63 ) . The median time to death or distant metastasis was 28.3 months in the durvalumab group and 16.2 months in the placebo group ( stratified hazard ratio , 0.53 ; 95 % CI , 0.41 to 0.68 ) . A total of 30.5 % of the patients in the durvalumab group and 26.1 % of those in the placebo group had grade 3 or 4 adverse events of any cause ; 15.4 % and 9.8 % of the patients , respectively , discontinued the trial regimen because of adverse events . CONCLUSIONS Durvalumab therapy result ed in significantly longer overall survival than placebo . No new safety signals were identified . ( Funded by AstraZeneca ; PACIFIC Clinical Trials.gov number , NCT02125461 . |
13,816 | 31,366,382 | Seven days after starting primaquine , G6PD normal patients had a 0.3 % ( 1/389 ) risk of clinical ly significant haemolysis ( fall in haemoglobin > 25 % to < 7 g/dL ) and a 1 % ( 4/389 ) risk of a fall in haemoglobin > 5 g/dL. Conclusions Primaquine has the potential to reduce malaria-related anaemia at day 42 and beyond by preventing recurrent parasitaemia . | Background Malaria causes a reduction in haemoglobin that is compounded by primaquine , particularly in patients with glucose-6-phosphate dehydrogenase ( G6PD ) deficiency .
The aim of this study was to determine the relative contributions to red cell loss of malaria and primaquine in patients with uncomplicated Plasmodium vivax . | Background Afghanistan 's national guidelines recommend chloroquine for the treatment of Plasmodium vivax infection , the parasite responsible for the majority of its malaria burden . Chloroquine resistance in P. vivax is emerging in Asia . Therapeutic responses across Afghanistan have not been evaluated in detail . Methods Between July 2007 and February 2009 , an open-label , r and omized controlled trial of chloroquine and dihydroartemisinin-piperaquine in patients aged three months and over with slide-confirmed P. vivax mono-infections was conducted . Consistent with current national guidelines , primaquine was not administered . Subjects were followed up daily during the acute phase of illness ( days 0 - 3 ) and weekly until day 56 . The primary endpoint was the overall cumulative parasitological failure rate at day 56 after the start of treatment , with the hypothesis being that dihydroartemisinin-piperaquine was non-inferior compared to chloroquine ( Δ = 5 % difference in proportion of failures ) . Results Of 2,182 individuals with positive blood films for P. vivax , 536 were enrolled in the trial . The day 28 cure rate was 100 % in both treatment groups . Parasite clearance was more rapid with dihydroartemisinin-piperaquine than chloroquine . At day 56 , there were more recurrent infections in the chloroquine arm ( 8.9 % , 95 % CI 6.0 - 13.1 % ) than the dihydroartemisinin-piperaquine arm ( 2.8 % , 95 % CI 1.4 - 5.8 % ) , a difference in cumulative recurrence rate of 6.1 % ( 2-sided 90%CI + 2.6 to + 9.7 % ) . The log-rank test comparing the survival curves confirmed the superiority of dihydroartemisinin-piperaquine over chloroquine ( p = 0.003 ) . Multivariate analysis showed that a lower initial haemoglobin concentration was also independently associated with recurrence . Both regimens were well tolerated and no serious adverse events were reported . Conclusions Chloroquine remains an efficacious treatment for the treatment of vivax malaria in Afghanistan . In a setting where radical therapy can not be administered , dihydroartemisinin-piperaquine provides additional benefit in terms of post-treatment prophylaxis , reducing the incidence of recurrence from 4 - 8 weeks after treatment . Trial Registration The trial was registered at Clinical Trials.gov under identifier NCT00682578 Background Malaria is a very important cause of anaemia in tropical countries . Anaemia is assessed either by measurement of the haematocrit or the haemoglobin concentration . For comparisons across studies , it is often necessary to derive one measure from the other . Methods Data on patients with slide-confirmed uncomplicated falciparum malaria were pooled from 85 antimalarial drug trials conducted in 25 different countries , to assess the haemoglobin/haematocrit relationship at different time points in malaria . Using a linear r and om effects model , a conversion equation for haematocrit was derived based on 3,254 measurements from various time points ( ranging from day 0 to day 63 ) from 1,810 patients with simultaneous measurements of both parameters . Haemoglobin was also estimated from haematocrit with the commonly used threefold conversion . Results A good fit was obtained using Haematocrit = 5.62 + 2.60 * Haemoglobin . On average , haematocrit/3 levels were slightly higher than haemoglobin measurements with a mean difference ( ± SD ) of -0.69 ( ± 1.3 ) for children under the age of 5 ( n = 1,440 measurements from 449 patients ) . Conclusion Based on this large data set , an accurate and robust conversion factor both in acute malaria and in convalescence was obtained . The commonly used threefold conversion is also valid Background Radical cure of Plasmodium vivax malaria with 8-aminoquinolines ( primaquine or tafenoquine ) is complicated by haemolysis in individuals with glucose-6-phosphate dehydrogenase ( G6PD ) deficiency . G6PD heterozygous females , because of individual variation in the pattern of X-chromosome inactivation ( Lyonisation ) in erythroid cells , may have low G6PD activity in the majority of their erythrocytes , yet are usually reported as G6PD “ normal ” by current phenotypic screening tests . Their haemolytic risk when treated with 8-aminoquinolines has not been well characterized . Methods and Findings In a cohort study nested within a r and omised clinical trial that compared different treatment regimens for P. vivax malaria , patients with a normal st and ard NADPH fluorescent spot test result ( ≳30%–40 % of normal G6PD activity ) were r and omised to receive 3 d of chloroquine or dihydroartemisinin-piperaquine in combination with primaquine , either the st and ard high dose of 0.5 mg base/kg/day for 14 d or a higher dose of 1 mg base/kg/d for 7 d. Patterns of haemolysis were compared between G6PD wild-type and G6PD heterozygous female participants . Between 21 February 2012 and 04 July 2014 , 241 female participants were enrolled , of whom 34 were heterozygous for the G6PD Mahidol variant . Haemolysis was substantially greater and a larger proportion of participants reached the threshold of clinical ly significant haemolysis ( fractional haematocrit reduction > 25 % ) in G6PD heterozygotes taking the higher ( 7 d ) primaquine dose ( 9/17 [ 53 % ] ) compared with G6PD heterozygotes taking the st and ard high ( 14 d ) dose ( 2/16 [ 13 % ] ; p = 0.022 ) . In heterozygotes , the mean fractional haematocrit reductions were correspondingly greater with the higher primaquine dose ( 7-d regimen ) : −20.4 % ( 95 % CI −26.0 % to −14.8 % ) ( nadir on day 5 ) compared with the st and ard high ( 14 d ) dose : −13.1 % ( 95 % CI −17.6 % to −8.6 % ) ( nadir day 6 ) . Two heterozygotes taking the higher ( 7 d ) primaquine dose required blood transfusion . In wild-type participants , mean haematocrit reductions were clinical ly insignificant and similar with both doses : −5.8 ( 95 % CI −7.2 % to −4.4 % ) ( nadir day 3 ) compared with −5.5 % ( 95 % CI −7.4 % to −3.7 % ) ( nadir day 4 ) , respectively . Limitations to this nested cohort study are that the primary objective of the trial was design ed to measure efficacy and not haemolysis in relation to G6PD genotype and that the heterozygote groups were small . Conclusion Higher daily doses of primaquine have the potential to cause clinical ly significant haemolysis in G6PD heterozygous females who are reported as phenotypically normal with current point of care tests . Trial Registration Clinical Trials.gov NCT01640574 Background New antimalarials are needed for P. vivax and P. falciparum malaria . This study compared the efficacy and safety of pyronaridine-artesunate with that of chloroquine for the treatment of uncomplicated P. vivax malaria . Methods and Findings This phase III r and omized , double-blind , non-inferiority trial included five centers across Cambodia , Thail and , India , and Indonesia . In a double-dummy design , patients ( aged > 3–≤60 years ) with microscopically confirmed P. vivax mono-infection were r and omized ( 1∶1 ) to receive pyronaridine-artesunate ( target dose 7.2∶2.4 mg/kg to 13.8∶4.6 mg/kg ) or chloroquine ( st and ard dose ) once daily for three days . Each treatment group included 228 r and omized patients . Outcomes for the primary endpoint , Day-14 cure rate in the per- protocol population , were 99.5 % , ( 217/218 ; 95%CI 97.5 , 100 ) with pyronaridine-artesunate and 100 % ( 209/209 ; 95%CI 98.3 , 100 ) with chloroquine . Pyronaridine was non-inferior to chloroquine : treatment difference −0.5 % ( 95%CI −2.6 , 1.4 ) , i.e. , the lower limit of the 2-sided 95%CI for the treatment difference was greater than −10 % . Pyronaridine-artesunate cure rates were non-inferior to chloroquine for Days 21 , 28 , 35 and 42 . Parasite clearance time was shorter with pyronaridine-artesunate ( median 23.0 h ) versus chloroquine ( 32.0 h ; p<0.0001 ) , as was fever clearance time ( median 15.9 h and 23.8 h , respectively ; p = 0.0017 ) . Kaplan-Meier estimates of post-baseline P. falciparum infection incidence until Day 42 were 2.5 % with pyronaridine-artesunate , 6.1 % with chloroquine ( p = 0.048 , log-rank test ) . Post-baseline P. vivax or P. falciparum infection incidence until Day 42 was 6.8 % and 12.4 % , respectively ( p = 0.022 , log rank test ) . There were no deaths . Adverse events occurred in 92/228 ( 40.4 % ) patients with pyronaridine-artesunate and 72/228 ( 31.6 % ) with chloroquine . Mild and transient increases in hepatic enzymes were observed for pyronaridine-artesunate . Conclusion Pyronaridine-artesunate efficacy in acute uncomplicated P. vivax malaria was at least that of chloroquine . As pyronaridine-artesunate is also efficacious against P. falciparum malaria , this combination has potential utility as a global antimalarial drug . Trial registration Clinical trials.gov Background Severe malaria ( SM ) is classically associated with Plasmodium falciparum infection . Little information is available on the contribution of P. vivax to severe disease . There are some epidemiological indications that P. vivax or mixed infections protect against complications and deaths . A large morbidity surveillance conducted in an area where the four species coexist allowed us to estimate rates of SM among patients infected with one or several species . Methods and Findings This was a prospect i ve cohort study conducted within the framework of the Malaria Vaccine Epidemiology and Evaluation Project . All presumptive malaria cases presenting at two rural health facilities over an 8-y period were investigated with history taking , clinical examination , and laboratory assessment . Case definition of SM was based on the World Health Organization ( WHO ) criteria adapted for the setting ( i.e. , clinical diagnosis of malaria associated with asexual blood stage parasitaemia and recent history of fits , or coma , or respiratory distress , or anaemia [ haemoglobin < 5 g/dl ] ) . Out of 17,201 presumptive malaria cases , 9,537 ( 55 % ) had a confirmed Plasmodium parasitaemia . Among those , 6.2 % ( 95 % confidence interval [ CI ] 5.7%–6.8 % ) fulfilled the case definition of SM , most of them in children < 5 y. In this age group , the proportion of SM was 11.7 % ( 10.4%–13.2 % ) for P. falciparum , 8.8 % ( 7.1%–10.7 % ) for P. vivax , and 17.3 % ( 11.7%–24.2 % ) for mixed P. falciparum and P. vivax infections . P. vivax SM presented more often with respiratory distress than did P. falciparum ( 60 % versus 41 % , p = 0.002 ) , but less often with anaemia ( 19 % versus 41 % , p = 0.0001 ) . Conclusion P. vivax monoinfections as well as mixed Plasmodium infections are associated with SM . There is no indication that mixed infections protected against SM . Interventions targeted toward P. falciparum only might be insufficient to eliminate the overall malaria burden , and especially severe disease , in areas where P. falciparum and P. vivax coexist Azithromycin has demonstrated activity in a prevention of Plasmodium vivax infection , but no controlled treatment studies have been performed . We conducted a double-blinded trial in P. vivax malaria in which patients were r and omized to either azithromycin 1,000 mg q.d . x 3 or chloroquine 600 mg q.d . x 2 then 300 mg on Day 3 followed by primaquine on Days 7 through 20 . Eighty-five of 97 ( 88 % ) of those on azithromycin and 101 of 102 ( 99 % ) of those on chloroquine [ difference 11 % ; 95 % CI : -18 , -4 ] were clinical ly cured at Day 7 . The Day 28 results were similar [ 89 % versus 99 % , azithromycin versus chloroquine , respectively ] . Parasitologic success was seen in 81 of 97 ( 84 % ) on azithromycin and 100 of 102 ( 98 % ) on chloroquine [ difference 14 % ; 95 % CI : -22 , -6 ] . The median parasite clearance time was 55 hours on azithromycin and 20 hours on chloroquine ( P < 0.001 ) . Drug-related adverse events were seen in 13 of 98 ( 13 % ) on azithromycin and 24 of 102 ( 24 % ) on chloroquine ( P = 0.062 ) . Resolution of parasitemia was significantly faster with chloroquine compared with azithromycin , but azithromycin was better tolerated . These data provide support for further study of azithromycin to better define its role in the treatment of P. vivax malaria , either alone as second-line treatment or in combination with other active therapies Background The Bangladeshi national treatment guidelines for uncomplicated malaria follow WHO recommendations but without G6PD testing prior to primaquine administration . A prospect i ve observational study was conducted to assess the efficacy of the current antimalarial policy . Methods Patients with uncomplicated malaria , confirmed by microscopy , attending a health care facility in the Chittagong Hill Tracts , Bangladesh , were treated with artemether-lumefantrine ( days 0–2 ) plus single dose primaquine ( 0.75mg/kg on day2 ) for P. falciparum infections , or with chloroquine ( days 0–2 ) plus 14 days primaquine ( 3.5mg/kg total over 14 days ) for P. vivax infections . Hb was measured on days 0 , 2 and 9 in all patients and also on days 16 and 30 in patients with P. vivax infection . Participants were followed for 30 days . The study was registered with the clinical trials website ( NCT02389374 ) . Results Between September 2014 and February 2015 a total of 181 patients were enrolled ( 64 % P. falciparum , 30 % P. vivax and 6 % mixed infections ) . Median parasite clearance times were 22.0 ( Interquartile Range , IQR : 15.2–27.3 ) hours for P. falciparum , 20.0 ( IQR : 9.5–22.7 ) hours for P. vivax and 16.6 ( IQR : 10.0–46.0 ) hours for mixed infections . All participants were afebrile within 48 hours , two patients with P. falciparum infection remained parasitemic at 48 hours . No patient had recurrent parasitaemia within 30 days . Adjusted male median G6PD activity was 7.82U/gHb . One male participant ( 1/174 ) had severe G6PD deficiency ( < 10 % activity ) , five participants ( 5/174 ) had mild G6PD deficiency ( 10–60 % activity ) . The Hb nadir occurred on day 2 prior to primaquine treatment in P. falciparum and P. vivax infected patients ; mean fractional fall in Hb was -8.8 % ( 95%CI -6.7 % to -11.0 % ) and -7.4 % ( 95%CI : -4.5 to -10.4 % ) respectively . Conclusion The current antimalarial policy remains effective . The prevalence of G6PD deficiency was low . Main contribution to haemolysis in G6PD normal individuals was attributable to acute malaria rather than primaquine administration . Trial Registration Clinical Trials.gov Background Recent efforts in malaria control have result ed in great gains in reducing the burden of Plasmodium falciparum , but P. vivax has been more refractory . Its ability to form dormant liver stages confounds control and elimination efforts . To compare the efficacy and safety of primaquine regimens for radical cure , we undertook a r and omized controlled trial in Ethiopia . Methods and findings Patients with normal glucose-6-phosphate dehydrogenase status with symptomatic P. vivax mono-infection were enrolled and r and omly assigned to receive either chloroquine ( CQ ) or artemether-lumefantrine ( AL ) , alone or in combination with 14 d of semi-supervised primaquine ( PQ ) ( 3.5 mg/kg total ) . A total of 398 patients ( n = 104 in the CQ arm , n = 100 in the AL arm , n = 102 in the CQ+PQ arm , and n = 92 in the AL+PQ arm ) were followed for 1 y , and recurrent episodes were treated with the same treatment allocated at enrolment . The primary endpoints were the risk of P. vivax recurrence at day 28 and at day 42 . The risk of recurrent P. vivax infection at day 28 was 4.0 % ( 95 % CI 1.5%–10.4 % ) after CQ treatment and 0 % ( 95 % CI 0%–4.0 % ) after CQ+PQ . The corresponding risks were 12.0 % ( 95 % CI 6.8%–20.6 % ) following AL alone and 2.3 % ( 95 % CI 0.6%–9.0 % ) following AL+PQ . On day 42 , the risk was 18.7 % ( 95 % CI 12.2%–28.0 % ) after CQ , 1.2 % ( 95 % CI 0.2%–8.0 % ) after CQ+PQ , 29.9 % ( 95 % CI 21.6%–40.5 % ) after AL , and 5.9 % ( 95 % CI 2.4%–13.5 % ) after AL+PQ ( overall p < 0.001 ) . In those not prescribed PQ , the risk of recurrence by day 42 appeared greater following AL treatment than CQ treatment ( HR = 1.8 [ 95 % CI 1.0–3.2 ] ; p = 0.059 ) . At the end of follow-up , the incidence rate of P. vivax was 2.2 episodes/person-year for patients treated with CQ compared to 0.4 for patients treated with CQ+PQ ( rate ratio : 5.1 [ 95 % CI 2.9–9.1 ] ; p < 0.001 ) and 2.3 episodes/person-year for AL compared to 0.5 for AL+PQ ( rate ratio : 6.4 [ 95 % CI 3.6–11.3 ] ; p < 0.001 ) . There was no difference in the occurrence of adverse events between treatment arms . The main limitations of the study were the early termination of the trial and the omission of haemoglobin measurement after day 42 , result ing in an inability to estimate the cumulative risk of anaemia . Conclusions Despite evidence of CQ-resistant P. vivax , the risk of recurrence in this study was greater following treatment with AL unless it was combined with a supervised course of PQ . PQ combined with either CQ or AL was well tolerated and reduced recurrence of vivax malaria by 5-fold at 1 y. Trial registration Clinical Trials.gov Background Chloroquine is an anti-malarial drug being used to treat Plasmodium vivax malaria cases in Ethiopia . However , emergence of chloroquine resistant strains of the parasite has challenged the current efficacy of the drug . Therefore , the aim of this study was to assess the effectiveness of chloroquine against P. vivax strains in one of the malaria endemic areas of Ethiopia , namely Halaba district , located in South Nations and Nationalities Peoples Region ( SNNPR ) of South Ethiopia Results Among 87 malaria patients enrolled in the study , only 80 of them completed the 28-days follow-up . Seven of them dropped from the study for different reasons . Among those study participants that completed their follow-up , 69 were classified under the category of adequate clinical and parasitological response ( ACPR ) . However , the remaining 11 cases were considered as under treatment failure mainly due to recurrence of parasitemia on day 7 ( four patients ) , day 14 ( six patients ) , and day 21 ( one patient ) . The age of all cases of treatment failures was found to be less than 20 years . The load of parasitemia of patients with treatment failure on day of admission ( 4709.4/μl ) was higher than day of recurrence ( 372.37/μl ) . Parasite reduction ratio ( PRR ) of treatment failure cases was 12.6/μl . Conclusion This report revealed the rise in treatment failure ( 13 % [ 95 % CI = 0.074 - 0.217 ] ) as compared to earlier reports from Ethiopia . It signals the spreading of chloroquine resistant P. vivax ( CRPv ) strains to malaria endemic areas of Ethiopia . It is recommended that all concerned bodies should act aggressively before further expansion of the current drug resistant malaria Background Plasmodium vivax has a dormant hepatic stage , called the hypnozoite , which can cause relapse months after the initial attack . For 50 years , primaquine has been used as a hypnozoitocide to radically cure P. vivax infection , but major concerns remain regarding the side-effects of the drug and adherence to the 14-day regimen . This study examined the effectiveness of using the directly-observed therapy ( DOT ) method for the radical treatment of P. vivax malaria infection , to prevent reappearance of the parasite within the 90-day follow-up period . Other potential risk factors for the reappearance of P. vivax were also explored . Methods A r and omized trial was conducted from May 2007 to January 2009 in a low malaria transmission area along the Thai-Myanmar border . Patients aged ≥ 3 years diagnosed with P. vivax by microscopy , were recruited . All patients were treated with the national st and ard regimen of chloroquine for three days followed by primaquine for 14 days . Patients were r and omized to receive DOT or self-administered therapy ( SAT ) . All patients were followed for three months to check for any reappearance of P. vivax . Results Of the 216 patients enrolled , 109 were r and omized to DOT and 107 to SAT . All patients recovered without serious adverse effects . The vivax reappearance rate was significantly lower in the DOT group than the SAT group ( 3.4/10,000 person-days vs. 13.5/10,000 person-days , p = 0.021 ) . Factors related to the reappearance of vivax malaria included inadequate total primaquine dosage received ( < 2.75 mg/kg ) , duration of fever ≤ 2 days before initiation of treatment , parasite count on admission ≥ 10,000/µl , multiple P. vivax-genotype infection , and presence of P. falciparum infection during the follow-up period . Conclusions Adherence to the 14-day primaquine regimen is important for the radical cure of P. vivax malaria infection . Implementation of DOT reduces the reappearance rate of the parasite , and may subsequently decrease P. vivax transmission in the area The efficacy of chloroquine in the treatment of Plasmodium vivax malaria is declining on the Northwestern border of Thail and . This r and omized controlled trial in 500 adults and children shows that dihydroartemisinin-piperaquine is a safe and effective alternative treatment BACKGROUND Plasmodium knowlesi commonly causes severe malaria in Malaysian Borneo , with high case-fatality rates reported . We compared risk , spectrum , and outcome of severe disease from P. knowlesi , Plasmodium falciparum , and Plasmodium vivax and outcomes following introduction of protocol s for early referral and intravenous artesunate for all severe malaria . METHODS From September 2010 to October 2011 we prospect ively assessed nonpregnant patients aged ≥12 years admitted to Queen Elizabeth Hospital ( QEH ) , Sabah , with polymerase chain reaction-confirmed Plasmodium monoinfection . St and ardized referral and prereferral intravenous artesunate were instituted at district hospitals . RESULTS Severe malaria occurred in 38 of 130 ( 29 % ) patients with P. knowlesi , 13 of 122 ( 11 % ) with P. falciparum , and 7 of 43 ( 16 % ) with P. vivax . The commonest severity criteria in knowlesi malaria included parasitemia > 100 000/µL ( n = 18 ) , jaundice ( n = 20 ) , respiratory distress ( n = 14 ) , hypotension ( n = 13 ) , and acute kidney injury ( n = 9 ) . On multivariate analysis , P. knowlesi was associated with a 2.96-fold ( 95 % confidence interval , 1.19 - 7.38-fold ) greater risk of severity than P. falciparum ( P = .020 ) ; only parasitemia and schizontemia > 10 % independently predicted knowlesi severity . Risk of severe knowlesi malaria increased 11-fold with parasitemia > 20 000/µL , and 28-fold with parasitemia > 100 000/µL. Nearly all ( 92 % ) knowlesi malaria patients received oral artemisinin therapy ; 36 of 38 ( 95 % ) and 39 of 92 ( 42 % ) with severe and nonsevere disease , respectively , also received ≥1 dose of intravenous artesunate . No deaths occurred from any species . CONCLUSIONS Plasmodium knowlesi is the commonest cause of severe malaria at QEH , with parasitemia the major risk factor for severity . Early referral and treatment with artesunate was highly effective for severe malaria from all species and associated with zero mortality CONTEXT In areas where Plasmodium falciparum and Plasmodium vivax coexist and treatments for the 2 species differ , misdiagnosis can lead to poor outcomes in either disease . A unified therapy effective against both species would reduce reliance on species-specific diagnosis , which in many areas is difficult to maintain . The antifolates are an important and affordable antimalarial class to which it is often assumed P vivax malaria is intrinsically resistant . OBJECTIVE To test the relative efficacy and safety of 2 antifolate drugs against P vivax malaria and compare each with chloroquine . DESIGN , SETTING , AND PATIENTS An open-label r and omized controlled trial comparing chloroquine , sulfadoxine-pyrimethamine , and chlorproguanil-dapsone for the treatment of P vivax malaria was conducted in eastern Afghanistan and northwestern Pakistan , areas in which P vivax malaria predominates . A total of 20,410 patients older than 3 years were screened ; 767 patients ( 315 in Pakistan and 452 in Afghanistan ) with confirmed P vivax malaria were enrolled and followed up daily for 4 days , then weekly for 28 days , between March 2004 and June 2006 . MAIN OUTCOME MEASURES Complete clearance of parasites with no recrudescence by day 14 . Secondary outcomes included being parasite-free by day 28 , clinical failure , and anemia . RESULTS By day 14 , only 1 patient in the sulfadoxine-pyrimethamine group had parasites . By day 28 , failure rates were found in 2 of 153 patients ( 1.3 % ) in the chloroquine group , 5 of 290 patients ( 1.7 % ) in the sulfadoxine-pyrimethamine group , and 27 of 272 patients ( 9.9 % ) in the chlorproguanil-dapsone group . Chlorproguanil-dapsone was less effective than sulfadoxine-pyrimethamine ( adjusted odds ratio [ OR ] , 6.4 ; 95 % confidence interval [ CI ] , 2.4 - 17.0 ; P<.001 ) and chloroquine ( adjusted OR , 8.4 ; 95 % CI , 2.0 - 36.5 ; P = .004 ) . Chloroquine and sulfadoxine-pyrimethamine were equivalent in efficacy at day 28 ( adjusted OR , 1.3 ; 95 % CI , 0.3 - 7.0 ; P = .73 ) . Chloroquine cleared gametocytes and asexual parasites more rapidly than sulfadoxine-pyrimethamine or chlorproguanil-dapsone did . All drugs were well tolerated . CONCLUSIONS Although chloroquine remains the drug of choice , antifolates are effective against P vivax malaria in South Asia . These drugs may be appropriate for unified treatment where species-specific diagnosis is unavailable , most likely in combination with other drugs . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00158561 Background Chloroquine was used as first-line treatment for Plasmodium falciparum or Plasmodium vivax in Indonesia before the initial launch of artemisinin combination therapy in 2004 . A study to evaluate efficacies of chloroquine against P. falciparum and P. vivax was undertaken at Lampung in southern Sumatra , western Indonesia in 2002 . Methods Patients infected by P. falciparum or P. vivax were treated with 25 mg/kg chloroquine base in three daily doses over 48 hr . Finger prick blood was collected on Days 0 , 2 , 3 , 7 , 14 , 21 and 28 after starting drug administration . Whole blood chloroquine and its desethyl metabolite were measured on Days-0 , -3 and -28 , or on the day of recurrent parasitaemia . Results 42 patients infected by P. falciparum were enrolled , and 38 fullfilled criteria for per protocol analysis . Only six of 38 ( 16 % ) showed a response consistent with senstivity to chloroquine . 25 of 32 failures were confirmed resistant by demonstrating chloroquine levels on day of recurrence exceeding the minimally effective concentration ( 200 ng/mL whole blood ) . The 28-day cumulative incidence of resistance in P. falciparum was 68 % ( 95 % CI : 0.5260 - 0.8306 ) . Thirty one patients infected by P. vivax were enrolled , and 23 were evaluable for per protocol analysis . 15 out of 23 ( 65 % ) subjects had persistent or recurrent parasitaemia . Measurement of chloroquine levels confirmed all treatment failures prior to Day-15 as resistant . Beyond Day-15 , 4 of 7 recurrences also had drug levels above 100 ng/mL and were classified as resistant . The 28-day cumulative incidence of chloroquine resistance in P. vivax was 43 % ( 95 % CI : 0.2715 - 0.6384 ) . Conclusion These findings confirm persistantly high levels of resistance to chloroquine by P. falciparum in southern Sumatra , and suggest that high- grade and frequent resistance to chloroquine by P. vivax may be spreading westward in the Indonesia archipelago BACKGROUND During the period of 1996 - 1999 , we prospect ively monitored 243 Javanese adults and children after arriving in Papua , Indonesia , and microscopically documented each new case of malaria by active surveillance . METHODS In a r and omized , open-label , comparative malaria treatment trial , 72 adults and 50 children received chloroquine for each incident case of malaria , and 74 adults and 47 children received mefloquine . RESULTS Among 975 primary treatment courses , the cumulative 28-day curative efficacies were 26 % and 82 % for chloroquine against Plasmodium falciparum malaria and Plasmodium vivax malaria , respectively . Mefloquine cure rates were far superior ( 96 % against P. falciparum malaria and 99.6 % against P. vivax malaria ) . CONCLUSIONS Mefloquine is a useful alternative treatment for P. vivax malaria and P. falciparum malaria in areas such as Papua , where chloroquine is still recommended as the first-line therapeutic agent Background There are very few drugs that prevent the relapse of Plasmodium vivax malaria in man . Tinidazole is a 5-nitroimidazole approved in the USA for the treatment of indications including amoebiasis and giardiasis . In the non-human primate relapsing Plasmodium cynomolgi/macaque malaria model , tinidazole cured one of six macaques studied with an apparent mild delay to relapse in the other five of 14–28 days compared to 11–12 days in controls . One study has demonstrated activity against P. vivax in man . Presented here are the results of a pilot phase II , r and omized , open-label study conducted along the Thai-Myanmar border design ed to evaluate the efficacy of tinidazole to prevent relapse of P. vivax when administered with chloroquine . Methods This study utilized a modified triangular test sequential analysis which allows repeated statistical evaluation during the course of enrolment while maintaining a specified power and type 1 error and minimizing recruitment of subjects . Enrolment was to be halted when a pre-specified success/failure ratio was surpassed . The study was design ed to have a 5 % type 1 error and 90 % power to show whether tinidazole would produce a relapse rate of less than 20 % or greater than 45 % through Day 63 of weekly follow-up after initiation of treatment and initial parasite clearance with 3 days of an oral weight based dosing of chloroquine and five days of 2 grams/day of tinidazole . Results All subjects cleared their parasitaemia by Day 3 . Six of the first seven subjects treated with tinidazole relapsed prior to Day 63 ( average Day 48.3 ( range 42–56 ) ) . This exceeded the upper boundary of the triangular test and enrolment to receive tinidazole was halted . A concurrent cohort of five subjects definitively treated with st and ard doses of primaquine and chloroquine ( historically 100 % effective ) showed no episodes of recurrent P. vivax parasitaemia during the 63-day protocol specified follow-up period . Conclusions Tinidazole is ineffective in preventing relapse of P. vivax at the dose used . The macaque relapsing model appeared to correctly predict outcome in humans . Use of the modified triangular test allowed minimal enrolment and limited unnecessary exposure to the study drug and reduced costs . This adds weight to the ethical and economic advantages of this study design to evaluate similarly situated drugs . Trial registration Clinical Trials.gov Background . Primaquine is used to eradicate latent Plasmodium vivax parasite from liver , with administration of st and ard dose daily up to 14 days . We studied efficacy , safety , and tolerability of sustained release ( SR ) formulation of primaquine in comparison with conventional primaquine in preventing relapse of P. vivax malaria . Methods . Microscopically confirmed cases of P. vivax malaria received chloroquine therapy for three days . Aparasitemic and asymptomatic patients were then r and omized to receive either conventional primaquine 15 mg for 14 days or primaquine SR 15 mg for 14 days , or primaquine SR 30 mg for seven days . Results . Of the 360 patients , who received chloroquine therapy , 358 patients were r and omized . Two-hundred eighty-eight patients completed six-month follow-up and four patients ( three : conventional primaquine 15 mg ( 2.86 % ) , one : primaquine SR 30 mg ( 0.93 % ) ) showed relapse confirmed by PCR genotyping . Drug compliance was significantly better in primaquine SR 30 mg group ( 95.57 % , p = 0.039 ) without any serious adverse events . Conclusion . Primaquine SR 15 mg and primaquine SR 30 mg could be an effective alternative to conventional primaquine 15 mg due to their comparable cure rates and safety profile . Shorter treatment duration with primaquine SR 30 mg may increase patient compliance and may further reduce relapse rates . Clinical Trial Registration . This trial is registered with CTRI/2010/091/000245 ABSTRACT Plasmodium vivax malaria , though benign , has now become a matter of concern due to recent reports of life-threatening severity and development of parasite resistance to different antimalarial drugs . The magnitude of the problem is still undetermined . The present study was undertaken to determine the in vivo efficacy of chloroquine ( CQ ) and chloroquine plus primaquine in P. vivax malaria in Kolkata and polymorphisms in the pvmdr1 and pvcrt-o genes . A total of 250 patients with P. vivax monoinfection were recruited and r and omized into two groups , A and B ; treated with chloroquine and chloroquine plus primaquine , respectively ; and followed up for 42 days according to the WHO protocol of 2009 . Data were analyzed using per- protocol analyses . We assessed polymorphisms of the pvmdr1 and pvcrt-o genes by a DNA-sequencing method . Out of the 250 patients recruited , 204 completed a 42-day follow-up period , 101 in group A and 103 in group B. In group A , the non-PCR-corrected efficacy of CQ was 99 % ( 95 % confidence interval [ CI ] , 0.944 to 1.00 ) , and in group B , all cases were classified as adequate clinical and parasitological response ( ACPR ) . Day 3 positivity was observed in 11 ( 5.3 % ) cases . No specific mutation pattern was recorded in the pvcrt-o gene . Eight nonsynonymous mutations were found in the pvmdr1 gene , three of which were new . The Y976F mutation was not detected in any isolate . Chloroquine , either alone or in combination with primaquine , is still effective against P. vivax malaria in the study area . ( The study protocol was registered in CTRI [ Clinical Trial Registry-India ] of the Indian council of Medical Research under registration no. CTRI/2011/09/002031 . We studied the antirelapse efficacy of a supervised 14-d 15 mg/d regimen of primaquine therapy ( n = 131 ) compared with no antirelapse therapy ( n = 142 ) in 273 patients with confirmed Plasmodium vivax malaria in Mumbai , India , between July 1998 and April 2000 . There were 6/131 ( 4.6 % ) recurrences in patients given primaquine compared with 13/142 ( 9.2 % ) in those not given antirelapse therapy . In the 14-d primaquine group , polymerase chain reaction-single str and conformational polymorphism ( PCR-SSCP ) genotyping analysis of pre- and post-treatment blood sample s was done for the 6 patients who had a recurrence of parasitaemia and the results gave a true relapse rate of 2.29 % ( 3/131 ) , 2 sample s were classified as reinfections and 1 sample did not amplify . Our results indicate probable resistance to the 14-d regimen of primaquine for the first time in India and illustrate the need to ( i ) monitor patients given this regimen and ( ii ) carry out comparative studies between primaquine and new drugs such as tafenoquine and bulaquine for preventing relapses Background Multidrug-resistant Plasmodium vivax ( Pv ) is widespread in eastern Indonesia , and emerging elsewhere in Asia-Pacific and South America , but is generally regarded as a benign disease . The aim of the study was to review the spectrum of disease associated with malaria due to Pv and P. falciparum ( Pf ) in patients presenting to a hospital in Timika , southern Papua , Indonesia . Methods and Findings Data were prospect ively collected from all patients attending the outpatient and inpatient departments of the only hospital in the region using systematic data forms and hospital computerised records . Between January 2004 and December 2007 , clinical malaria was present in 16 % ( 60,226/373,450 ) of hospital out patients and 32 % ( 12,171/37,800 ) of in patients . Among patients admitted with slide-confirmed malaria , 64 % of patients had Pf , 24 % Pv , and 10.5 % mixed infections . The proportion of malarial admissions attributable to Pv rose to 47 % ( 415/887 ) in children under 1 y of age . Severe disease was present in 2,634 ( 22 % ) in patients with malaria , with the risk greater among Pv ( 23 % [ 675/2,937 ] ) infections compared to Pf ( 20 % [ 1,570/7,817 ] ; odds ratio [ OR ] = 1.19 [ 95 % confidence interval ( CI ) 1.08–1.32 ] , p = 0.001 ) , and greatest in patients with mixed infections ( 31 % [ 389/1,273 ] ) ; overall p < 0.0001 . Severe anaemia ( haemoglobin < 5 g/dl ) was the major complication associated with Pv , accounting for 87 % ( 589/675 ) of severe disease compared to 73 % ( 1,144/1,570 ) of severe manifestations with Pf ( p < 0.001 ) . Pure Pv infection was also present in 78 patients with respiratory distress and 42 patients with coma . In total 242 ( 2.0 % ) patients with malaria died during admission : 2.2 % ( 167/7,722 ) with Pf , 1.6 % ( 46/2,916 ) with Pv , and 2.3 % ( 29/1260 ) with mixed infections ( p = 0.126 ) . Conclusions In this region with established high- grade chloroquine resistance to both Pv and Pf , Pv is associated with severe and fatal malaria particularly in young children . The epidemiology of P. vivax needs to be re-examined elsewhere where chloroquine resistance is increasing Background Intravascular hemolysis is an intrinsic feature of severe malaria pathophysiology but the pathogenic role of cell-free hemoglobin-mediated oxidative stress in severe malaria associated acute kidney injury ( AKI ) is unknown . Methods As part of a prospect i ve observational study , enrolment plasma cell-free hemoglobin ( CFH ) , lipid peroxidation markers ( F2-isoprostanes ( F2-IsoPs ) and isofurans ( IsoFs ) ) , red cell deformability , and serum creatinine were quantified in Bangladeshi patients with severe falciparum malaria ( n = 107 ) , uncomplicated malaria ( n = 80 ) and sepsis ( n = 28 ) . The relationships between these indices and kidney function and clinical outcomes were examined . Results AKI was diagnosed at enrolment in 58 % ( 62/107 ) of consecutive patients with severe malaria , defined by an increase in creatinine ≥1.5 times expected baseline . Severe malaria patients with AKI had significantly higher plasma cell-free hemoglobin ( geometric mean CFH : 8.8 μM ; 95 % CI , 6.2–12.3 μM ) , F2-isoprostane ( 56.7 pg/ml ; 95 % CI , 45.3–71.0 pg/ml ) and isofuran ( 109.2 pg/ml ; 95 % CI , 85.1–140.1 pg/ml ) concentrations on enrolment compared to those without AKI ( CFH : 5.1 μM ; 95 % CI , 4.0–6.6 μM ; P = 0.018 ; F2-IsoPs : 27.8 pg/ml ; 95 % CI , 23.7–32.7 pg/ml ; P < 0.001 ; IsoFs : 41.7 pg/ml ; 95 % CI , 30.2–57.6 pg/ml ; P < 0.001 ) . Cell-free hemoglobin correlated with markers of hemolysis , parasite burden ( P. falciparum histidine rich protein 2 ( PfHRP2 ) ) , and F2-IsoPs . Plasma F2-IsoPs and IsoFs inversely correlated with pH , positively correlated with creatinine , PfHRP2 and fractional excretion of sodium , and were higher in patients later requiring hemodialysis . Plasma F2-IsoP concentrations also inversely correlated with red cell deformability and were higher in fatal cases . Mixed effects modeling including an interaction term for CFH and time showed that F2-IsoPs , IsoFs , PfHRP2 , CFH , and red cell rigidity were independently associated with increasing creatinine over 72 h. Multivariable logistic regression showed that admission F2-IsoPs , IsoFs and red cell deformability were associated with the need for subsequent hemodialysis . Conclusions Cell-free hemoglobin and lipid peroxidation are associated with acute kidney injury and disease severity in falciparum malaria , suggesting a pathophysiological role in renal tubular injury . Evaluation of adjunctive therapies targeting cell-free hemoglobin-mediated oxidative stress is warranted Background Of late there have been accounts of therapeutic failure and chloroquine resistance in Plasmodium vivax malaria especially from Southeast Asian regions . The present study was conducted to assess the therapeutic efficacy of chloroquine – primaquine ( CQ – PQ ) combined regimen in a cohort of uncomplicated P. vivax mono-infection . Methods A tertiary care hospital-based prospect i ve study was conducted among adult cohort with mono-infection P. vivax malaria as per the World Health Organization ’s protocol of in vivo assessment of anti-malarial therapeutic efficacy . Participants were treated with CQ 25 mg/kg body weight divided over 3 days and PQ 0.25 mg/kg body weight daily for 2 weeks . Results Of a total of 125 participants recruited , 122 ( 97.6 % ) completed day 28 follow up , three ( 2.4 % ) participants were lost to follow-up . Eight patients ( 6.4 % ) were ascertained to have mixed P. vivax and Plasmodium falciparum infection by nested polymerase chain reaction test . The majority of subjects ( 56.8 % , 71/125 ) became aparasitaemic on day 2 followed by 35.2 % ( 44/125 ) on day 3 , and 8 % ( 10/125 ) on day 7 , and remained so thereafter . Overall only one therapeutic failure ( 0.8 % , 1/125 ) occurred on day 3 due to persistence of fever and parasitaemia . Conclusions CQ – PQ combined regimen remains outst and ingly effective for uncomplicated P. vivax malaria and should be retained as treatment of choice in the study region . One case of treatment failure indicates possible resistance which warrants constant vigilance and periodic surveillance Chloroquine (CQ)-resistant Plasmodium vivax was first documented in 1989 and threatens much of eastern Indonesia , with > 50 % of therapeutic failure rates . We screened 2236 subjects for malaria infection through active case detection and identified 232 infected cases with 100 subjects carried P. vivax mono infection . We prospect ively evaluated therapeutic responses to CQ in 73 subjects infected by P. vivax in northeastern Papua , Indonesia . We phenotyped these infections as susceptible or resistant to CQ using a 28-day in vivo test format . Eighteen subjects ( 25 % ) had persistent or recurrent parasitemia during the test and were provisionally classified as resistant . Among the remainder , 46 ( 63 % ) subjects had no persistent or recurrent parasitemia and were classified as having infections sensitive to CQ , 4 were lost to follow up , and 5 dropped out . Among the 18 provisionally resistant cases , 1 subject ( 6 % ) had persistent parasitemia at Day 3 and was considered as a direct treatment failure , 2 subjects ( 11 % ) had recurrent parasitemia by Day 7 and were considered early treatment failures , and 7 ( 39 % ) and 8 ( 44 % ) had recurrent parasitemia by Days 14 and 28 , respectively . Analysis of blood for CQ+N-desethylchloroquine ( DCQ ) levels on day of recurrence from 15 of the 18 with treatment failures showed 11 subjects having CQ+DCQ blood levels ⩾ 100 ng/ml and 2 with CQ+DCQ blood levels < 100 ng/ml . The 28-day cumulative incidence of therapeutic failure likely due to parasite resistance was 17.5 % . These findings affirm P. vivax resistance to CQ in eastern Indonesia , albeit at lower levels than reported elsewhere . This simple means of phenotyping P. vivax infections could be implemented in other malaria endemic areas of Indonesia Chloroquine ( CQ ) is an effective treatment of choice for vivax malaria in most setting s , but with the spread of CQ-resistant Plasmodium falciparum , many countries now use artemisinin-based combination therapy for treatment of falciparum malaria . In areas co-endemic for falciparum and vivax malaria incorrect differential diagnosis is always a risk . In Afghanistan the adoption of sulfadoxine-pyrimethamine plus artesunate ( SP+AS ) as first-line falciparum treatment raises the prospect of a significant proportion of vivax malaria being misdiagnosed and treated with the combination . SP is considered to have limited efficacy against vivax malaria , and the efficacy of SP+AS against Plasmodium vivax has not been established in areas that are using SP+AS . A r and omised , non-inferiority trial comparing SP+AS with CQ monotherapy was undertaken on 190 vivax malaria patients in eastern Afghanistan . St and ard WHO procedures for in vivo evaluation of antimalarial drugs were followed . A total of 180 individuals completed the trial to day 42 . Using a per protocol analysis , both regimens result ed in > or = 96 % treatment success at 28 d , but significantly more cases failed in the CQ arm ( 46 % ) than in the SP+AS arm ( 24 % ) by day 42 . In areas where vivax infections might be misdiagnosed as falciparum infections and treated with SP+AS , patient management would be as good , or better than , with the st and ard CQ treatment Background Vivax malaria remains a major cause of morbidity in the subtropics . To undermine the stability of the disease , drugs are required that prevent relapse and provide reservoir reduction . A 14-day course of primaquine ( PQ ) is effective but can not safely be used in routine practice because of its interaction with glucose-6-phosphate dehydrogenase ( G6PD ) deficiency for which testing is seldom available . Safe and effective use of PQ without the need for G6PD testing would be ideal . The efficacy and safety of an 8-week , once weekly PQ regimen was compared with current st and ard treatment ( chloroquine alone ) and a 14-day PQ regimen . Methods and Principal Findings 200 microscopically confirmed Plasmodium vivax patients were r and omly assigned to either once weekly 8-week PQ ( 0.75mg/kg/week ) , once weekly 8-week placebo , or 14-day PQ ( 0.5mg/kg/day ) in North West Frontier Province , Pakistan . All patients were treated with a st and ard chloroquine dose and tested for G6PD deficiency . Deficient patients were assigned to the 8-week PQ group . Failure was defined as any subsequent episode of vivax malaria over 11 months of observation . There were 22/71 ( 31.0 % ) failures in the placebo group and 1/55 ( 1.8 % ) and 4/75 ( 5.1 % ) failures in the 14-day and 8-week PQ groups , respectively . Adjusted odds ratios were : for 8-week PQ vs. placebo-0.05 ( 95%CI : 0.01 - 0.2 , p<0.001 ) and for 14-day PQ vs. placebo-0.01 ( 95%CI : 0.002 - 0.1 , p<0.001 ) . Restricted analysis allowing for a post-treatment prophylactic effect confirmed that the 8-week regimen was superior to current treatment . Only one G6PD deficient patient presented . There were no serious adverse events . Conclusions A practical radical treatment for vivax malaria is essential for control and elimination of the disease . The 8-week PQ course is more effective at preventing relapse than current treatment with chloroquine alone . Widespread use of the 8-week regimen could make an important contribution to reservoir reduction or regional elimination where G6PD testing is not available . Trial Registration Clinical Trials.gov Abstract Background Malaria remains a major public health problem , with half the world population at risk of contracting malaria . The effects of Plasmodium vivax on prosperity and longevity have been highlighted in several recent clinical case reports . The first line of vivax treatment drugs has seen no radical innovation for more than 60 years . This study introduces a subtle incremental innovation to vivax treatment : a chloroquine and primaquine co-blister . The co-blister includes a new chloroquine formulation incorporating coated tablets to mask the drug ’s bitter taste and user-friendly packaging containing tablets of each drug , which may improve patient adherence and facilitate the appropriate use of the drugs . This new formulation will replace the non-coated chloroquine distributed in Brazil . Methods Patients were orally treated with 150 mg coated chloroquine tablets for 3 days : an initial 450 mg dose , followed by two 300 mg doses . The patients were treated concomitantly with two 15 mg primaquine tablets for 7–9 days , according to their weight . The primary objective of this study was to prove parasitological and clinical cure rates above 90 % by day 28 . Results This single-arm open-label non-comparative trial was conducted according to the WHO recommended methodology for the surveillance of anti-malarial drug efficacy in the Brazilian Amazon . On day 28 , the parasitological and clinical response was adequate in 98.8 % of patients ( CI 95 % 93.4–100 % ) . The success rate on day 3 was 100 % , and the cumulative success rate by day 28 was 98.8 % ( CI 95 % 91.7–99.8 % ) . There were no serious adverse events , with most adverse events classified as mild . The pharmacokinetic parameters of chloroquine analysed in whole blood dry spot sample s showed mean ( coefficient of variation ) Cmax and AUC0–t values of 374.44 ( 0.35 ) and 3700.43 ( 0.36 ) ng/mL , respectively . Discussion This study reports an appropriate safety and efficacy profile of a new formulation of coated chloroquine tablets for vivax malaria treatment in the Brazilian Amazon . The cure rates meet the WHO efficacy criteria , supporting current Brazilian guidelines and the use of the formulation for vivax malaria treatment . Nevertheless , further studies should be conducted to address adherence and the effectiveness of the formulation . Trial registration RBR-77q7t3-UTN : U1111 - 1121 - 2982 . Registered 10th May Background Malaria is a major public health problem in Nepal inflicted primarily by the parasite Plasmodium vivax , - the only species responsible for relapse cases in Nepal . Knowledge on its relapse rate is important for successful malaria control , but is lacking in Nepal . The information on circulating predominant genotypes of P. vivax is equally relevant for high endemic districts of Nepal to underst and the transmission dynamics of the parasite and to uncover the coverage and efficacy of potential vaccine beforeh and . Methods A prospect i ve observational study with a six months follow-up period was conducted from August 2010 to May 2011 in four health centres of Kailali and Kanchanpur districts of Nepal to access the relapse/re-infection rate of P. vivax . The prevalence and heterogeneity of its genotypes were identified by PCR-RFLP assay targeting central repeat region of circumsporozoite protein ( Pvcsp ) . Results In total , 137 cases microscopically suspected to have P. vivax infection were enrolled in the study . Of these , 23 cases ( 17 % ) were detected for the relapse/ re-infection-during a six-month period , with a high proportion being male cases of age group 11–20 years . For genotyping , 100 whole blood sample s were analysed , of which 95 % of the parasite isolates were found to be of VK210 genotype . The minor genotype VK247 existed either in isolation or as mixed infection with VK210 in rest of the sample s. Conclusions The relapse/re-infection rate of 17 % was determined for P. vivax in Kailali and Kanchanpur districts of Nepal . A heterogeneous Pvcsp genotypic distribution of P. vivax was detected with VK210 being a predominant type , suggesting a complex transmission dynamics of the parasite . Exp and ing such study in other endemic regions of Nepal would help provide a complete picture on relapse/re-infection rate and parasite genotypic variability that can help in effective control and management of malaria in Nepal Background Plasmodium knowlesi is a cause of symptomatic and potentially fatal infections in humans . There are no studies assessing the detailed parasitological response to treatment of knowlesi malaria infections in man and whether antimalarial resistance occurs . Methods A prospect i ve observational study of oral chloroquine and primaquine therapy was conducted in consecutive patients admitted to Kapit Hospital , Sarawak , Malaysian Borneo with PCR-confirmed single P. knowlesi infections . These patients were given oral chloroquine for three days , and at 24 hours oral primaquine was administered for two consecutive days , primarily as a gametocidal agent . Clinical and parasitological responses were recorded at 6-hourly intervals during the first 24 hours , daily until discharge and then weekly to day 28 . Vivax malaria patients were studied as a comparator group . Results Of 96 knowlesi malaria patients who met the study criteria , 73 were recruited to an assessment of the acute response to treatment and 60 completed follow-up over 28 days . On admission , the mean parasite stage distributions were 49.5 % , 41.5 % , 4.0 % and 5.6 % for early trophozoites , late trophozoites , schizonts and gametocytes respectively . The median fever clearance time was 26.5 [ inter-quartile range 16 - 34 ] hours . The mean times to 50 % ( PCT50 ) and 90 % ( PCT90 ) parasite clearance were 3.1 ( 95 % confidence intervals [ CI ] 2.8 - 3.4 ) hours and 10.3 ( 9.4 - 11.4 ) hours . These were more rapid than in a group of 23 patients with vivax malaria 6.3 ( 5.3 - 7.8 ) hours and 20.9 ( 17.6 - 25.9 ) hours ; P = 0.02 ) . It was difficult to assess the effect of primaquine on P. knowlesi parasites , due to the rapid anti-malarial properties of chloroquine and since primaquine was administered 24 hours after chloroquine . No P. knowlesi recrudescences or re-infections were detected by PCR . Conclusions Chloroquine plus primaqine is an inexpensive and highly effective treatment for uncomplicated knowlesi malaria infections in humans and there is no evidence of drug resistance . Further studies using alternative anti-malarial drugs , including artemisinin derivatives , would be desirable to define optimal management strategies for P. knowlesi Background In Mexico , combined chloroquine ( CQ ) and primaquine ( PQ ) treatment has been used since the late 1950s to treat Plasmodium vivax infections . Although malaria transmission has declined , current treatment strategies must be evaluated to advance towards malaria elimination . Methods The clinical and parasitological outcome of treating symptomatic P. vivax with the 14-day ( T14 ) treatment or intermittent single dose ( ISD ) regimen was evaluated in southern Mexico between February 2008 and September 2010 . Patients over 12 months old with P. vivax mono-infection and asexual parasitaemia ≥500 parasites/µl were treated under supervision . After diagnosis ( day 0 ) , treatment began immediately . T14 patients received CQ for 3 days ( 10 , 10 and 5 mg/kg ) and PQ daily for 14 days ( 0.25 mg/kg ) , while ISD patients received a single dose of CQ ( 10 mg/kg ) and PQ ( 0.75 mg/kg ) on days 0 , 30 , 60 , 180 , 210 , and 240 . Follow-up was done by observing clinical and laboratory ( by microscopy , serology and PCR ) outcome , considering two endpoints : primary blood infection clearance and clinical response at ~28 days , and the incidence of recurrent blood infection during 12 months . Parasite genotypes of primary /recurrent blood infections were analysed . Results During the first 28 days , no differences in parasite clearance or clinical outcome were observed between T14 ( 86 patients ) and ISD ( 67 patients ) . On day 3 , 95 % of patients in both groups showed no blood parasites , and no recurrences were detected on days 7–28 . Contrarily , the therapeutic effectiveness ( absence of recurrent parasitaemia ) was distinct for T14 versus ISD at 12 months : 83.7 versus 50 % , respectively ( p = 0.000 ) . Symptomatic and asymptomatic infections were recorded on days 31–352 . Some parasite recurrences were detected by PCR and /or serological testing . Conclusions T14 was effective for opportune elimination of the primary blood infection and preventing relapse episodes . The first single dose of CQ-PQ eliminated primary blood infection as efficiently as the initial three-dose scheme of T14 , but the ISD regimen should be ab and oned . A single combined dose administered to symptomatic patients in remote areas while awaiting parasitological diagnosis may contribute to halting P. vivax transmission . Alternatives for meeting the challenge of T14 supervision are discussed . Trial registration : NIH-USA , Clinical Trial.gov Identifier : A total of 128 Vietnamese patients with symptomatic Plasmodium vivax mono-infections were enrolled in a prospect i ve , open-label , r and omized trial to receive either chloroquine or dihydroartemisinin – piperaquine ( DHA-PPQ ) . The proportions of patients with adequate clinical and parasitological responses were 47 % in the chloroquine arm ( 31 of 65 patients ) and 66 % in the DHA-PPQ arm ( 42 of 63 patients ) in the Kaplan – Meier intention-to-treat analysis ( absolute difference 19 % , 95 % confidence interval = 0–37 % ) , thus establishing non-inferiority of DHA-PPQ . Fever clearance time ( median 24 versus 12 hours , P = 0.02 ) , parasite clearance time ( median 36 versus 18 hours , P < 0.001 ) , and parasite clearance half-life ( mean 3.98 versus 1.80 hours , P < 0.001 ) were all significantly shorter in the DHA-PPQ arm . All cases of recurrent parasitemia in the chloroquine arm occurred from day 33 onward , with corresponding whole blood chloroquine concentration lower than 100 ng/mL in all patients . Chloroquine thus remains efficacious for the treatment of P. vivax malaria in southern Vietnam , but DHA-PPQ provides more rapid symptomatic and parasitological recovery Summary To determine the level of antimalarial drug resistance in southern Papua , Indonesia , we assessed the therapeutic efficacy of chloroquine plus sulfadoxine – pyrimethamine ( CQ+SP ) for Plasmodium falciparum infections as well as CQ monotherapy for P. vivax infections . Patients with P. falciparum failing therapy were re-treated with unsupervised quinine ± doxycycline therapy and those with P. vivax with either unsupervised quinine ± doxycycline or amodiaquine . In total , 143 patients were enrolled in the study ( 103 treated with CQ+SP and 40 with CQ ) . Early treatment failures occurred in four patients ( 4 % ) with P. falciparum and six patients ( 15 % ) with P. vivax . The failure rate by Day 28 for P. vivax was 65 % ( 95 % CI 49–81 ) . After PCR correction for re-infections , the Day 42 recrudescence rate for P. falciparum infections was 48 % ( 95 % CI 31–65 ) . Re-treatment with unsupervised quinine ± doxycycline result ed in further recurrence of malaria in 48 % ( 95 % CI 31–65 ) of P. falciparum infections and 70 % ( 95 % CI 37–100 ) of P. vivax infections . Eleven patients with recurrent P. vivax were re-treated with amodiaquine ; there were no early or late treatment failures . In southern Papua , a high prevalence of drug resistance of P. falciparum and P. vivax exists both to first- and second-line therapies . Preliminary data indicate that amodiaquine retains superior efficacy compared with CQ for CQ-resistant P. vivax Background Plasmodium vivax is the main malaria parasite in China , and China is now making efforts to eliminate malaria by 2020 . Radical cure of vivax malaria is one of challenges for malaria elimination . The purpose is to evaluate the efficacy and safety of artemisinin-naphthoquine ( ANQ ) versus chloroquine-primaquine ( CQ-PQ ) in treatment of vivax malaria in Yunnan Province , China . Methods An open-label r and omized and non-inferiority design , eligible patients with monoinfections of P. vivax were r and omly assigned to receive either a total target dose of ANQ 24.5 mg/kg ( naphthoquine 7 mg/kg and artemisinin 17.5 mg/kg ) , once a day for three days , or a total CQ dose of 24 mg base/kg , once a day for three days plus a PQ dose of 0.45 mg base/kg/day , once a day for eight days . Patients were followed up for one year . The difference in efficacy between ANQ and CQ-PQ was compared via Wilson ’s test . Results By day 42 , the number of patients free of recurrence was 125 ( 98.4 % ; 95 % Confidence interval , 94.4 - 99.8 % ) for ANQ arm and 123 ( 96.1 % ; 95%CI , 91.1 - 98.7 % ) for CQ-PQ , and non-significant ( P = 0.4496 ) . By day 365 , the number was 101 ( 79.5 % ; 95%CI , 71.8 - 85.9 % ) for ANQ and 106 ( 82.8 % ; 95%CI , 75.1 - 88.9 % ) for CQ-PQ , and non-significant ( P = 0.610 ) . So the proportions of patients free of recurrence had no significant difference between ANQ and CQ-PQ groups by day 28 , 42 and 365 ; compared with CQ-PQ , the side effect of ANQ was mild . Conclusion ANQ is non-inferior to CQ-PQ in terms of patients free of recurrence , and safer than CQ-PQ Abstract Background Plasmodium vivax malaria is an important public health issue in the Amazon region , and it accounts for approximately 84 % of cases of the disease . Migration across the border between Brazil and French Guiana contributes to the maintenance of the disease . The aim of this study was to evaluate the therapeutic and parasitological responses of patients with P. vivax malaria treated with chloroquine and primaquine in the socio-environmental context of cross-border interactions between Brazil and French Guiana . The factors controlled were diagnostic agreement , adherence , adjustment of primaquine doses for patient weight , and quality of the drugs used . Methods A prospect i ve study was conducted in 2011 with 103 individuals aged 10–60 years with a positive diagnosis of P. vivax treated with chloroquine ( 10 mg base/kg on the first day , followed by 7.5 mg/kg on the second and third days ) and primaquine for 7 days , who were followed for 28 days . The primaquine doses were adjusted for the patients ’ weight . A number of factors were determined : epidemiological characteristics , origin of patients , signs and symptoms , initial parasitaemia and parasitaemia clearance time , blood concentrations of chloroquine and primaquine , quality of anti-malarial drugs and diagnostic agreement . Results Ninety-five patients were followed for 28 days . There was a 100 % agreement in microscopic diagnosis between field laboratory and reference centre . The adhesion to the treatment was 100 % . Of these patients , 32.6 % received a weight-adjusted dose of primaquine . The chloroquine and primaquine tablets were consistent with the optimal quality limits for human consumption . The investigated patients achieved optimal blood exposure to anti-malarial drugs . The parasitological and therapeutic response was adequate in 99.0 % of cases . Conclusions In the municipality of Oiapoque , the therapeutic regime used for the treatment of P. vivax malaria using chloroquine combined with primaquine remains effective , when external factors are controlled , such as the quality of anti-malarial drugs , the adhesion to the treatment prescribed , the correct diagnostic and the adjustment of primaquine dose for patient body weight Background . Despite increasing evidence of the development of Plasmodium vivax chloroquine ( CQ ) resistance , there have been no trials comparing its efficacy with that of artemisinin-based combination therapies ( ACTs ) in Latin America . Methods . This r and omized controlled trial compared the antischizontocidal efficacy and safety of a 3-day supervised treatment of the fixed-dose combination artesunate-amodiaquine Winthrop ® ( ASAQ ) versus CQ for treatment of uncomplicated P. vivax infection in Manaus , Brazil . Patients were followed for 42 days . Primary endpoints were adequate clinical and parasitological responses ( ACPR ) rates at day 28 . Genotype-adjustment was performed . Results . From 2012 to 2013 , 380 patients were enrolled . In the per- protocol ( PP ) analysis , adjusted-ACPR was achieved in 100 % ( 165/165 ) and 93.6 % ( 161/172 ) of patients in the ASAQ and CQ arm ( difference 6.4 % , 95 % CI 2.7 % ; 10.1 % ) at day 28 and in 97.4 % ( 151/155 ) and 77.7 % ( 129/166 ) , respectively ( difference 19.7 % , 95 % CI 12.9 % ; 26.5 % ) , at day 42 . Apart from ITT D28 assessment , superiority of ASAQ on ACPR was demonstrated . ASAQ presented faster clearance of parasitaemia and fever . Based on CQ blood level measurements , CQ resistance prevalence was estimated at 11.5 % ( 95 % CI : 7.5 - 17.3 ) up to day 42 . At least one emergent adverse event ( AE ) was recorded for 79/190 ( 41x6 % ) in the ASAQ group and for 85/190 ( 44x7 % ) in the CQ group . Both treatments had similar safety profiles . Conclusions . ASAQ exhibited high efficacy against CQ resistant P. vivax and is an adequate alternative in the study area . Studies with an efficacious comparator , longer follow-up and genotype-adjustment can improve CQR characterization . Clinical Trials Registration . NCT01378286 Abstract Background Chloroquine has been the treatment of choice for acute vivax malaria for more than 60 years . Malaria caused by Plasmodium vivax has recently shown resistance to chloroquine in some places . This study compared the efficacy and safety of fixed dose combination ( FDC ) of arterolane maleate and piperaquine phosphate ( PQP ) with chloroquine in the treatment of uncomplicated vivax malaria . Methods Patients aged 13–65 years with confirmed mono-infection of P. vivax along with fever or fever in the previous 48 h were included . The 317 eligible patients were r and omly assigned to receive FDC of arterolane maleate and PQP ( n = 159 ) or chloroquine ( n = 158 ) for 3 days . Primaquine was given as an anti-relapse measure on day 3 and continued for 14 consecutive days . Primary efficacy analysis included assessment of the proportion of aparasitaemic and afebrile patients at 72 h. Safety endpoints were analysis of adverse events , vital signs , laboratory data , and abnormalities on electrocardiograph . Patients participated in the study for at least 42 days . Results In per protocol population , the proportion of aparasitaemic and afebrile patients at 72 h was 100 % ( 140/140 ) in the FDC of arterolane maleate and PQP group , and 99.3 % ( 145/146 ) in the chloroquine group ( Fisher , p > 0.9999 ) . In intent to treat population , the corresponding value was reported to be 96.9 % ( 154/159 ) in the FDC of arterolane maleate and PQP group and 98.7 % ( 156/158 ) in the chloroquine group ( Fisher , p = 0.4479 ) . The median parasite clearance time was 24 h in FDC of arterolane maleate and PQP group and 26 h in chloroquine group ( Log-rank , p = 0.2264 ) . Similarly , median fever clearance time was 24 h in both the groups ( Log-rank , p = 0.7750 ) . In PP population , day 28 cure rates were 100 % in both the groups ( 95 % CI ( 96.52 , 100.0 for FDC of arterolane maleate and PQP and 96.73 , 100.0 in chloroquine group ) ) . Incidence of adverse events was 82.4 % in the FDC of arterolane maleate and PQP group and 85.4 % in the chloroquine group . Most of the adverse events were mild to moderate in intensity . The commonly reported clinical adverse events in the FDC of arterolane maleate and PQP versus chloroquine group were vomiting ( 5.0 vs 5.1 % ) , headache ( 1.3 vs 3.2 % ) and prolonged QT ( 1.9 vs 3.2 % ) . No deaths were reported . The pharmacokinetic analysis indicates that arterolane maleate is well absorbed and has a relatively short t1/2 of 3.2 h. Piperaquine is also well absorbed after oral administration with a t1/2 of about 228.33 h. Conclusions The study showed that FDC of arterolane maleate and PQP effectively cured vivax malaria and attained acceptable level of cure up to day 28 . Both the groups showed similar safety profile . Trial Registration Clinical Trial Registry India : Models for the analysis of longitudinal data must recognize the relationship between serial observations on the same unit . Multivariate models with general covariance structure are often difficult to apply to highly unbalanced data , whereas two-stage r and om-effects models can be used easily . In two-stage models , the probability distributions for the response vectors of different individuals belong to a single family , but some r and om-effects parameters vary across individuals , with a distribution specified at the second stage . A general family of models is discussed , which includes both growth models and repeated- measures models as special cases . A unified approach to fitting these models , based on a combination of empirical Bayes and maximum likelihood estimation of model parameters and using the EM algorithm , is discussed . Two examples are taken from a current epidemiological study of the health effects of air pollution Background Chloroquine ( CQ ) is the first-line treatment for vivax malaria in Ethiopia , but there is evidence for its declining efficacy . Defining the extent and regional distribution of CQ resistance is critical to ensure optimal treatment guidelines . This study aim ed to provide data on the therapeutic efficacy of CQ against Plasmodium vivax malaria in southern Ethiopia . Methods Patients with P. vivax mono-infection aged between 8 months and 65 years were enrolled in a clinical efficacy trial . The study was conducted at four sites in southern Ethiopia . Study participants were treated with a supervised course of CQ ( 25 mg/kg over three consecutive days ) , followed by weekly blood film examination and clinical assessment for 28 days . CQ blood concentrations were not assessed . The primary endpoint was the risk of failure at 28 days by survival analysis . Results Between May 2010 and December 2013 , 288 patients were enrolled in the study ( n = 89 in Shele , n = 52 in Guba , n = 57 in Batu and n = 90 in Shone ) . Baseline characteristics varied significantly between sites . In total 34 ( 11.8 % ) patients were censored during follow up ( five with Plasmodiumfalciparum parasitaemia and 29 lost to follow up ) . Two ( 0.7 % ) patients experienced early treatment failure and 23 ( 8 % ) late treatment failure . The overall risk of recurrence by day 28 was 9.4 % ( 95 % CI 6.4–13.6 % ) with site-specific estimates of 3.8 % ( 95 % CI 1.2–11.3 ) for Shele , 21.9 % ( 95 % CI 12.2–36.1 ) for Guba , 5.9 % ( 95 % CI 1.9–17.3 ) for Batu and 9.2 % ( 95 % CI 4.5–17.6 ) for Shone . Conclusion There is evidence of reduced CQ efficacy across three of the four study sites , with the degree of resistance severe enough in Guba to suggest that review of treatment policy may be warranted Background Resistance to anti-malarials is a major challenge for effective malaria control in sub-Saharan Africa . This triggered a need for routine monitoring of the efficacy of the antimalarial drugs every two years in all malaria endemic countries . Chloroquine remained the drug of choice for the treatment of vivax malaria in Ethiopia . Though , a strong scientific evidence of chloroquine resistance to P.vivax that could have brought change of treatment regimen is yet to be established in Ethiopia , continuous and regular monitoring of drug ’s efficacy is critical for establishing rational anti-malarial drug policies . This study therefore , assessed the therapeutic efficacy of Chloroquine ( CQ ) for the treatment of Plasmodium vivax infections in Northwestern Ethiopia . Methods An observational , 28- day therapeutic clinical efficacy study was conducted from August to December , 2014 , in Northwest Ethiopia . Patients confirmed to have monoinfection of vivax malaria , aged above 6 months were included . All subjects were treated with st and ard chloroquine dose of 25 mg/kg for three ( 3 ) days . Parasitological and clinical outcomes of treated patients were then evaluated on days 1 , 2 , 3 , 7 , 14 , 21 , and 28 during the entire 28-day follow-up period . A portable spectrophotometer ( HemoCue Hb 301 System , Sweden ) was used to estimate hemoglobin concentration . Results A total of 69 subjects had completed follow up . Some 57/69 ( 82.6 % ) had fever at enrolment and the rest 12 patients 48 hours before enrollment . Out of total , 65/69 ( 94.2 % ) and 66/69 ( 95.6 % ) of the study subjects were free of fever by day 1 and day 2 respectively but fever was cleared in all subjects by day 3 . At base line the mean asexual parasitemia was 3540 parasites/μL of blood . Parasite carriage on day 3 was 3 % . The overall cure rate ( an adequate and clinical parasitological response ) was very high ( 97 % ) [ ( 95 % CI = 93.1–99.4 ) ] . The time to parasite , fever and gametocyte clearance as expressed in mean ( SD ) was 35 ( 3 ) , 25 ( 4.6 ) , 28 ( 3.2 ) hours respectively . Mean hemoglobin was significantly increased ( P<0.001 ) from 12.2 ( 7–15 ) g/dl at day 0 to 13.3 ( 10–16 ) g/dl on day 28 . Conclusions In view of our findings , CQ remains efficacious for the treatment of vivax malaria in the study area . However , there is a need to monitor CQR regularly using molecular and or biochemical tools for better evaluation of treatment outcomes ABSTRACT Plasmodium vivax resistance to chloroquine ( CQ ) is currently reported in almost all countries where P. vivax is endemic . In Vietnam , despite a first report on P. vivax resistance to chloroquine published in the early 2000s , P. vivax was still considered sensitive to CQ . Between May 2009 and December 2011 , a 2-year cohort study was conducted in central Vietnam to assess the recommended radical cure regimen based on a 10-day course of primaquine ( 0.5 mg/kg/day ) together with 3 days of CQ ( 25 mg/kg ) . Here we report the results of the first 28-day follow-up estimating the cumulative risk of P. vivax recurrences together with the corresponding CQ blood concentrations , among other endpoints . Out of 260 recruited P. vivax patients , 240 completed treatment and were followed up to day 28 according to the WHO guidelines . Eight patients ( 3.45 % ) had a recurrent P. vivax infection , at day 14 ( n = 2 ) , day 21 ( n = 1 ) , and day 28 ( n = 5 ) . Chloroquine blood concentrations , available for 3/8 recurrent infections ( days 14 , 21 , and 28 ) , were above the MIC ( > 100 ng/ml whole blood ) in all of these cases . Fever and parasitemia ( both sexual and asexual stages ) were cleared by day 3 . Anemia was common at day 0 ( 35.8 % ) , especially in children under 10 years ( 50 % ) , and hemoglobin ( Hb ) recovery at day 28 was substantial among anemic patients ( median change from day 0 to 28 , + 1.7 g/dl ; interquartile range [ IQR ] , + 0.7 to + 3.2 ) . This report , based on CQ blood levels measured at the time of recurrences , confirms for the first time P. vivax CQ resistance in central Vietnam and calls for further studies using st and ardized protocol s for accurately monitoring the extent and evolution of P. vivax resistance to chloroquine in Vietnam . These results , together with the mounting evidence of artemisinin resistance in central Vietnam , further highlight the increasing threat of antimalarial drug resistance to malaria elimination in Vietnam Background . Efficacy of st and ard dose of primaquine ( PQ ) as antirelapse for P. vivax has decreased . We aim ed to assess efficacy of different PQ regimens . Methods . It was an open label , r and omized , controlled , parallel group , assessor blind study comparing antirelapse efficacy of 3 PQ regimens ( B = 15 mg/day × 14 days , C = 30 mg/day × 7 days , and D = 30 mg/day × 14 days ) with no PQ group ( A ) in P. vivax patients . Paired primary and recurrence sample s were subjected to 3 methods : ( i ) month of recurrence and genotyping , ( ii ) by PCR-RFLP , and ( iii ) PCR sequencing , to differentiate relapse and reinfection . The rates of recurrence relapse and reinfection were compared . Methods were compared for concordance between them . Results . The recurrence rate was 16.39 % , 8.07 % , 10.07 % , and 6.62 % in groups A , B , C , and D , respectively ( P = 0.004 ) . The relapse rate was 6.89 % , 1.55 % , 4 % , and 3.85 % as per the month of recurrence ; 8.2 % , 2 % , 4.58 % , and 3.68 % ( P = 0.007 ) as per PCR-RFLP ; and 2.73 % , 1.47 % , 1.55 % , and 1.53 % as per PCR sequencing for groups A , B , C , and D , respectively . The concordance between methods was low , 45 % . Conclusion . The higher recurrence rate in no PQ as compared to PQ groups documents PQ antirelapse activity . Regimens tested were safe . However , probable resistance to PQ warrants continuous monitoring and low concordance and limitations in the methods warrant caution in interpreting OBJECTIVE To describe India 's National Antimalarial Drug Resistance Monitoring System , measure the efficacy of first-line malaria treatments , and determine risk factors for treatment failure . METHODS In 2009 - 2010 , prospect i ve studies with 28 days of follow-up were conducted at 25 sentinel sites . Patients infected with Plasmodium falciparum were given artesunate plus sulfadoxine-pyrimethamine ( AS+SP ) ; those infected with P. vivax were given chloroquine . Polymerase chain reaction was used to distinguish post-treatment reinfection from treatment failure . Isolates of P. falciparum were checked for dhfr and dhps mutations . FINDINGS Overall , 1664 patients were enrolled . Kaplan-Meier survival analysis showed an efficacy of 98.8 % for AS+SP . Most patients with P. falciparum parasitaemia cleared their parasitaemias within 24 hours of treatment initiation , but six , including four with treatment failure , remained parasitaemic after 72 hours . Double mutants in dhfr were found in 68.4 % of the genotyped isolates . Triple or quadruple mutants in dhfr and mutations in dhps were rare . A daily dose of artesunate of < 3 mg per kg of body weight , age of less than 5 years , and fever at enrolment were associated with an increased risk of treatment failure . Chloroquine remained 100 % efficacious and generally cleared P. vivax parasitaemias within 48 hours . Vomiting ( seen in 47 patients ) was the most common adverse event . CONCLUSION India 's National Antimalarial Drug Resistance Monitoring System provides wide coverage . The first-line antimalarials used in the country remain safe and efficacious . The treatment of malaria in young children and the relative benefits of age- and weight-based dosing need further exploration Malaria regions of the Amazon basin have been characterized by difficult access and non-compliance of the patients to treatment . In an attempt to assess the schizonticide efficacy of chloroquine in a single dose of 600 mg , the authors realized a double-blind , placebo-controlled trial in 132 out patients with vivax malaria . Patients were distributed into two groups : group CPLA , given chloroquine 600 mg ( single dose ) on the first day of treatment , and two doses of placebo on second and third days . Group CHLO , given chloroquine 600 mg on first day and 450 mg on second and third day . Geometric means of the parasite density during the follow-up was similar in both groups . No differences were observed in the parasitological cure between the two groups ( p = 0.442 ) . There was clinical and parasitological efficacy in treatment of patients given a single-dose of chloroquine . This suggests that its restricted use could be indicated in remote areas of Brazilian Amazon Region , nevertheless the inadequate response of three patients indicates the need for further studies Plasmodium vivax is the second most important cause of morbidity in Ethiopia . There is , however , little information on P. vivax resistance to chloroquine and chloroquine plus primaquine treatment although these drugs have been used as the first line treatment for over 50 years . We assessed the efficacy of st and ard chloroquine and chloroquine plus primaquine treatment for P. vivax infections in a r and omized open-label comparative study in Debre Zeit and Nazareth in East Shoa , Ethiopia . A total of 290 patients with microscopically confirmed P. vivax malaria who presented to the outpatient setting s of the two laboratory centers were enrolled : 145 patients were r and omized to receive CQ and 145 to receive CQ+PQ treatment . Participants were followed-up for 28 - 157 days according to the WHO procedures . There were 12 ( 6.5 % ) lost to follow-up patients and 9 ( 3.1 % ) withdrawals . In all , 96 % ( 277/290 ) of patients were analysed at day 28 . Baseline characteristics were similar in all treatment groups . In all , 98.6 % ( 275/277 ) of patients had cleared their parasitemia on day 3 with no difference in mean parasite clearance time between regimens ( 48.34+/-17.68 , 50.67+/-15.70 h for the CQ and CQ+PQ group , respectively , P=0.25 ) . The cumulative incidence of therapeutic failure at day 28 by a life-table analysis method was 5.76 % ( 95 % CI : 2.2 - 14.61 ) and 0.75 % ( 95 % CI : 0.11 - 5.2 % ) in the CQ and CQ+PQ group , respectively ( P=0.19 ) . The relapse rate was 8 % ( 9/108 ) for the CQ group and 3 % ( 4/132 ) for the comparison group ( P=0.07 ) . The cumulative risk of relapse at day 157 by a life-table method was 61.8 % ( 95 % CI : 20.1 - 98.4 % ) in the CQ group , compared with 26.3 % ( 95 % CI : 7.5 - 29.4 % ) in the CQ+PQ group ( P=0.0038 ) . The study confirms the emergence of CQ and PQ resistance/treatment failure in P. vivax malaria in Ethiopia . Although treatment failures were detected , they were similar between the treatment groups . We recommend regular monitoring and periodic evaluation of the efficacy of these antimalarial drugs in systematic ally selected sentinel sites to detect further development of resistance and to make timely national antimalarial drug policy changes We conducted a study to compare the safety and tolerability of anti-relapse drugs elubaquine and primaquine against Plasmodium vivax malaria . After st and ard therapy with chloroquine , 30 mg/kg given over 3 days , 141 patients with P. vivax infection were r and omized to receive primaquine or elubaquine . The 2 treatment regimens were primaquine 30 mg once daily for 7 days ( group A , n = 71 ) , and elubaquine 25 mg once daily for 7 days ( group B , n = 70 ) . All patients cleared parasitemia within 7 days after chloroquine treatment . Among patients treated with primaquine , one patient relapsed on day 26 ; no relapse occurred with elubaquine treatement . Both drugs were well tolerated . Adverse effects occurred only in patients with G6PD deficiency who were treated with primaquine ( group A , n = 4 ) , whose mean hematocrit fell significantly on days 7 , 8 and 9 ( P = 0.015 , 0.027 , and 0.048 , respectively ) . No significant change in hematocrit was observed in patients with G6PD deficiency who were treated with elubaquine ( group B , n = 3 ) or in patients with normal G6PD . In conclusion , elubaquine , as anti-relapse therapy for P. vivax malaria , was as safe and well tolerated as primaquine and did not cause clinical ly significant hemolysis Fourty-eight patients infected by Plasmodium vivax were r and omly divided into chloroquine regimen groups A and B. Each case in group A received a total dosage of 1 200 mg(base ) over a 3-day period ( 600 mg on the first day then 300 mg daily ) . Cases in group B each received total dosage of 1 500 mg ( base ) in 3 days ( 750 mg on the first day then 375 mg daily ) . Body temperature and blood smears were examined on days 0 , 1 , 2 , 3 , 7 , 14 , 21 and 28 , respectively . All patients were negative for asexual parasites within 3 days . The cure rate on day 28 was 100 % . Results showed that P. vivax is sensitive to chloroquine in Laza , Myanmar , and chloroquine can still be used for the imported vivax malaria cases at the China-Myanmar border We conducted this prospect i ve study among 110 symptomatic Plasmodium vivax patients attending the Kasturba Hospital , Manipal , India , in order to evaluate their clinico-laboratory profile during July 2007–July 2009 . Complications observed among patients were : anaemia ( 46.4 % ; 95 % confidence interval [ CI ] , 37.08–55.72 % ) ; thrombocytopenia ( 68.2 % ; 95 % CI , 59.5–76.9 % ) ; leucopenia ( 29.1 % ; 95 % CI , 20.61–37.59 % ) ; hyperbilirubinaemia ( 20 % ; 95 % CI , 12.53–27.47 % ) ; non-oliguric renal failure ( 10.9 % ; 95 % CI , 5.08–16.72 % ) ; elevated serum transaminases ( 33.6 % ; 95 % CI , 24.77–42.43 % ) ; hypotension ( 8.2 % ; 95 % CI , 3.07–13.33 % ) ; hepatomegaly ( 27.3 % ; 95 % CI , 18.97–35.63 % ) ; and splenomegaly and jaundice in 12.7 % ( 95 % CI , 6.48–18.92 % ) . The 99 % chloroquine response and zero mortality observed in this study of vivax malaria are encouraging points for practicing physicians BACKGROUND Tafenoquine is an 8-aminoquinoline developed as a more effective replacement for primaquine . In a previous dose-ranging study in Thail and , 3 tafenoquine regimens with total doses ranging from 500 mg to 3000 mg prevented relapse of Plasmodium vivax malaria in most patients when administered 2 days after receipt of a blood schizonticidal dose of chloroquine . METHODS To improve convenience and to begin comparison of tafenoquine with primaquine , 80 patients with P. vivax infection were r and omized to receive 1 of the following 5 treatments 1 day after receiving a blood schizonticidal dose of chloroquine : ( A ) tafenoquine , 300 mg per day for 7 days ( n=18 ) ; ( B ) tafenoquine , 600 mg per day for 3 days ( n=19 ) ; ( C ) tafenoquine , 600 mg as a single dose ( n=18 ) ; ( D ) no further treatment ( n=13 ) ; or ( E ) primaquine base , 15 mg per day for 14 days ( n=12 ) . The minimum duration of protocol follow-up was 8 weeks , with additional follow-up to 24 weeks . RESULTS Forty-six of 55 tafenoquine recipients , 10 of 13 recipients of chloroquine only , and 12 of 12 recipients of chloroquine plus primaquine completed at least 8 weeks of follow-up ( or had relapse ) . There was 1 relapse among recipients of chloroquine plus tafenoquine , 8 among recipients of chloroquine only , and 3 among recipients of chloroquine plus primaquine . The rate of protective efficacy ( determined on the basis of reduction in incidence density ) for all recipients of chloroquine plus tafenoquine , compared with recipients of chloroquine plus primaquine , was 92.6 % ( 95 % confidence interval , 7.3%-99.9 % ; P=.042 , by Fisher 's exact test ) . CONCLUSIONS Tafenoquine doses as low as a single 600-mg dose may be useful for prevention of relapse of P. vivax malaria in Thail and with the objective of evaluating shortened therapeutic outlines effective in vivax malaria treatment , we accomplished an open , prospect i ve study allocating 234 patients with vivax malaria distributed at r and om into eight therapeutic groups . Six groups used oral arthemisin as blood esquizonticide at different doses for one day and the other two groups received chloroquine in a single dose . The primaquine was used as a hypnozoiticide in all groups . They received a daily dose of 30 mg in the course of five or seven days in all groups . The clearance of parasitaemia in patients treated with arthemisin ( independent of dosage ) was faster than the chloroquine group ( p < 0.01 ) . Cure was acheived in 92.3 % and 80.2 % , in patients treated with primaquine for seven or five days , respectively ( p=0.0372 ) For over 4 decades the antimalarial program in India has been prescribing a 5-day primaquine regimen as an antirelapse therapy to treat Plasmodium vivax malaria . In view of conflicting reports on the effectiveness of this regimen in the Indian subcontinent , and the varying prevalence of P. vivax in various ecosystems in India , the antirelapse efficacy of this regimen was evaluated in Orissa , a malaria endemic state in eastern India where P. falciparum predominates . In 723 cases of P. vivax infection treated with chloroquine alone and followed up weekly for 1 yr , the prevalence of recurrence of parasitaemia with fever was 8.6 % . Among another 759 P. vivax cases treated with chloroquine and a 5-day regimen of primaquine at 15 mg/day ( adult dose ) , the recurrence of infection was 6.5 % . The difference in recurrence was not significant ( P = 0.53 ) . It is important to note that in a great majority of cases of P. vivax in this area , infection did not recur even without treatment with primaquine . This finding , that the use of the 5-day primaquine regimen with chloroquine had no significant advantage over the use of chloroquine alone , undermines the rationale of using primaquine as an antirelapse drug in forested areas with a high prevalence of P. falciparum About 110 patients were enrolled to study the atypical presentations and the chloroquine sensitivity pattern of Plasmodium vivax malaria . The diagnosis was made from Giemsa stained peripheral blood smear . The co-infection of falciparum malaria was excluded both by smear and ParaSight F-test . After a thorough clinical work up , biochemical investigations were done . The fever clearance and parasite clearance time were determined in all cases . Absence of malarial paroxysm ( 22.8 per cent ) , migrainous headache ( 4.5 per cent ) , myalgia ( 6.3 per cent ) , episodic urticarial rash ( 1.8 per cent ) , relative bradycardia ( 13.6 per cent ) and postural hypotension ( 2.7 per cent ) were the atypical manifestations encountered . Besides this , severe forms like jaundice ( 7.2 per cent ) , cerebral involvement ( 0.9 per cent ) , severe anaemia ( 7.2 per cent ) , thrombocytopenia ( 3.6 per cent ) and pancytopenia ( 0.9 per cent ) had been detected . All , except the patient with cerebral involvement were treated with chloroquine patients responded well to the treatment except two ( 1.8 per cent ) patients who had chloroquine resistance . This study showed that vivax malaria can present with atypical and protean manifestations . The changing clinical profile along with development of chloroquine resistance may be considered as a warning signal Chloroquine-resistant Plasmodium vivax has not yet occurred in Vietnam . The efficacy of artemisinin for P. vivax was not established . We conducted a double-blind r and omized study involving 240 in patients with P. vivax malaria who received artemisinin ( 40 mg/kg over 3 days ) plus placebo chloroquine ( Art ) or chloroquine ( 25 mg/kg over 3 days ) plus placebo artemisinin ( Chl ) . Patients were followed up with weekly blood smears for 28 days . In each group 113 cases were analysed . All patients recovered rapidly . The median ( range ) parasite clearance time of regimen Art was 24 h ( 8 - 72 ) and of Chl 24 h ( 8 - 64 ; P = 0.3 ) . Parasites reappeared in two cases in each group on day 14 , in eight cases in each group ( 7 % ) on day 16 and in 25 ( 23 % ) and 18 ( 16 % ) cases , respectively , at the end of 4-week follow-up ( P = 0.3 ) . The population parasite clearance curve followed a mono-exponential decline . The parasite reduction ratio per 48 h reproduction cycle was 2.3 x 104 for both regimens . We conclude that artemisinin and chloroquine are equally effective in the treatment of P. vivax infections in Vietnam . Reappearance of parasites before day 16 ( 7 % ) suggests the emergence of chloroquine resistance . Three days of artemisinin monotherapy does not prevent recrudescence ABSTRACT The therapeutic responses to the eight most widely used antimalarial drugs were assessed in 207 adult patients withPlasmodium vivax malaria . This parasite does not cause marked sequestration , so parasite clearance can be used as a direct measure of antimalarial activity . The activities of these drugs in descending order were artesunate , artemether , chloroquine , mefloquine , quinine , halofantrine , primaquine , and pyrimethamine-sulfadoxine ( PS ) . Therapeutic responses to PS were poor ; parasitemias did not clear in 5 of the 12 PS-treated patients , whereas all the other patients made an initial recovery . Of 166 patients monitored for ≥28 days , 35 % had reappearance of vivax malaria 11 to 65 days later and 7 % developed falciparum malaria 5 to 21 days after the start of treatment . There were no significant differences in the times taken for vivax malaria reappearance among the different groups except for those given mefloquine and chloroquine , in which all vivax malaria reappearances developed > 28 days after treatment , suggesting suppression of the first relapse by these slowly eliminated drugs . There was no evidence of chloroquine resistance . The antimalarial drugs vary considerably in their intrinsic activities and stage specificities of action Abstract At a public hospital in Georgetown , Guyana , 44 patients seeking treatment for symptomatic , slide-confirmed malaria were given st and ard chloroquine ( CQ ) therapy and followed for 28 days . The patients apparently had pure infections with Plasmodium falciparum ( 14 ) , P. vivax ( 13 ) or P. malariae ( one ) , or mixed infections either of P. falciparum and P. vivax ( 17 ) or of P. falciparum , P. malariae and P. vivax ( two ) . Each received supervised treatment with 10 mg CQ base/kg on each of days 0 and 1 , and 5 mg/kg on day 2 . On the day of enrollment ( day 0 ) , the patients complained of fever ( 100 % ) , headache ( 100 % ) , malaise ( 94 % ) , myalgia ( 79 % ) , nausea ( 67 % ) , vertigo ( 49 % ) and vomiting ( 33 % ) . Many ( 39 % ) were ill enough to confine themselves to bed . On day 4 , fewer of the subjects complained of fever ( 15 % ) , headache ( 15 % ) , malaise ( 6 % ) , myalgia ( 21 % ) , nausea ( 6 % ) , vertigo ( 24 % ) or vomiting ( 0 % ) despite the relatively high ( > 48 % ) risk of therapeutic failure . The cumulative incidence of parasitological failure against P. falciparum was 15 % at day 4 , 33 % at day 7 and 48 % at day 14 . All of the P. vivax and P. malariae infections cleared before day 4 and none recurred by day 7 . Two infections with P. vivax recurred later ( on day 14 or 28 ) but in the presence of less than adequate , whole-blood concentrations of CQ plus desethyl-chloroquine ( i.e. < 100 ng/ml ) . Taken together , the results indicate a high risk of therapeutic failure of CQ against P. falciparum but also indicate that resistance to CQ in P. vivax occurs infrequently in Guyana The efficacy of chloroquine ( 25 mg base/kg over 3 days ) in Plasmodium vivax malaria was evaluated in 1995/96 in 342 patients living in an endemic area on the western border of Thail and . Clearance of fever and parasites was obtained within 2 days in > 95 % of the patients , and all were aparasitaemic by day 4 . Reappearance of P. vivax occurred in 1 patient on day 21 and in 8 by day 28 , giving a 28-day cure rate of 97 % [ 95 % confidence interval ( CI ) 95 - 99 % ] . By day 63 , the relapse/re-infection rate was 63 % ( 95 % CI 57 - 69 % ) . Most reappearances of parasitaemia ( 85 % ; 121/143 ) were symptomatic . These patients were retreated either with chloroquine alone ( n = 70 ) or with chloroquine and primaquine ( 0.25 mg/kg daily for 14 days ) ( n = 43 ) . Only 1 patient ( in the chloroquine-only group ) had prolonged parasite clearance ( D8 ) and he developed recurrent P. vivax by day 21 suggesting possible recrudescence . The addition of primaquine to chloroquine reduced the risk of having a third vivax episode within 2 months by 96 % ( 95 % CI 83 - 99 % ) . This result ed in a significantly higher haematocrit at day 42 despite a greater decrease in haematocrit during the first week of treatment with chloroquine-primaquine ( P = 0.04 ) . Chloroquine remains highly effective on the western border of Thail and and the use of strictly supervised primaquine effectively prevents relapse . The introduction of primaquine on a large scale in an endemic area still requires a long-term risk-benefit assessment which must take into account potential toxicity , low compliance and reductions in the incidence and severity of P. falciparum infections by co-existent P. vivax Chloroquine ( CQ ) is still the drug of choice for the treatment of vivax malaria in Ethiopia , whereas artemether-lumefantrine ( AL ) is for falciparum malaria . In this setting , clinical malaria cases are treated with AL . This necessitated the need to assess the effectiveness of AL for the treatment of Plasmodium vivax with CQ as a comparator . A total of 57 ( 80.3 % ) and 75 ( 85.2 % ) cases treated with CQ or AL , respectively , completed the study in an outpatient setting . At the end of the follow-up period of 28 days , a cumulative incidence of treatment failure of 7.5 % ( 95 % confidence interval [ CI ] = 2.9 - 18.9 % ) for CQ and 19 % ( 95 % CI = 11 - 31.6 % ) for AL was detected . CQ resistance was confirmed in three of five CQ treatment failures cases . The effectiveness of AL seems lower than CQ ; however , the findings were not conclusive , because the AL evening doses were not supervised The only available treatment that can eliminate the latent hypnozoite reservoir of vivax malaria is a 14 d course of primaquine ( PQ ) . A potential problem with long-course chemotherapy is the issue of compliance after clinical symptoms have subsided . The present study , carried out at an Afghan refugee camp in Pakistan , between June 2000 and August 2001 , compared 14 d treatment in supervised and unsupervised groups in which compliance was monitored by comparison of relapse rates . Clinical cases recruited by passive case detection were r and omised by family to placebo , supervised , or unsupervised groups , and treated with chloroquine ( 25 mg/kg ) over 3 days to eliminate erythrocytic stages . Individuals with glucose-6-phosphate dehydrogenase ( G6PD ) deficiency were excluded from the trial . Cases allocated to supervision were given directly observed treatment ( 0.25 mg PQ/kg body weight ) once per day for 14 days . Cases allocated to the unsupervised group were provided with 14 PQ doses upon enrollment and strongly advised to complete the course . A total of 595 cases were enrolled . After 9 months of follow up PQ proved equally protective against further episodes of P. vivax in supervised ( odds ratio 0.35 , 95 % CI 0.21 - 0.57 ) and unsupervised ( odds ratio 0.37 , 95 % CI 0.23 - 0.59 ) groups as compared to placebo . All age groups on supervised or unsupervised treatment showed a similar degree of protection even though the risk of relapse decreased with age . The study showed that a presumed problem of poor compliance may be overcome with simple health messages even when the majority of individuals are illiterate and without formal education . Unsupervised treatment with 14-day PQ when combined with simple instruction can avert a significant amount of the morbidity associated with relapse in population s where G6PD deficiency is either absent or readily diagnosable Plasmodium vivax malaria is an important cause of morbidity in Central and South America . In Colombia , this is the most prevalent malaria infection , representing 75 % of the reported cases . To define the efficacy of the chloroquine and primaquine regimen to eliminate hypnozoites and prevent relapses , we conducted a r and om controlled clinical trial of three primaquine regimens in an open-label study . We evaluated the anti-relapse efficacy of total primaquine doses of 45 , 105 , and 210 mg administered at a dosage of 15 mg/day in 210 adults with P. vivax infection from the northwestern region of Colombia . Cure rates for blood-stage P. vivax malaria by day 28 of follow-up were 100 % in all groups . Post-treatment reappearance of parasitemia during the six months of follow-up was 45 % , 36.6 % and 17.6 % , respectively , for each group . When compared with other groups , administration of 210 mg was a significant protection factor for reappearance of parasitemia in a malaria-endemic area In central China , Plasmodium vivax accounts for all of the native reported cases of malaria . Chloroquine ( CQ ) plus primaquine ( PQ ) have been used for more than 60 years as the frontline drugs , but the risk of treatment failure remains unknown . To measure the effectiveness and safety of CQ-PQ among vivax malaria patients , a total of 39 subjects with monoinfection vivax malaria was enrolled in a study from 2008 to 2009 . There were no recrudescence or danger signs observed within the 28-day follow-up period , showing that blood stage of P. vivax isolates from central China is still susceptible to CQ plus PQ combination therapy . However , the antirelapse efficacy of PQ is difficult to assess because of the high rate of loss to follow-up after 28 days ; also , parasites persisted in a single case at 3 days post-antimalarial drug treatment , indicating that continuous annual monitoring is needed in central China Combination therapy is one method of overcoming the global challenge of drug-resistant Plasmodium falciparum malaria . We conducted a hospital-based 28-day in vivo test comparing chloroquine/doxycycline to chloroquine or doxycycline alone for treating P. falciparum and Plasmodium vivax malaria in Irian Jaya , Indonesia . Eighty-nine patients with uncomplicated falciparum malaria were r and omized to st and ard dose chloroquine ( n = 30 ) , doxycycline ( 100 mg every 12 hours [ 7 days ] , n = 20 ) , or chloroquine with doxycycline ( n = 39 ) ; corresponding numbers for vivax malaria ( n = 63 ) were 23 , 16 , 24 . Endpoints were parasite sensitivity ( S ) or resistance ( RI/RII/RIII ) . Of the 105 evaluable patients , chloroquine/doxycycline cured ( S ) 20/22 ( 90.9 % [ 95 % CI 78.9 - 100 % ] ) patients with P. falciparum malaria ; 2/22 ( 9.1 % [ 0 - 21 % ] ) were RIII resistant . Doxycycline cured 11/17 ( 64.7 % [ 42.0 - 87.4 % ] ) patients , and chloroquine 4/20 ( 20 % [ 2.5 - 37.5 % ] ) . Against P. vivax , chloroquine/doxycycline cured ( S ) 12/17 ( 70.6 % [ 48.9 - 92.2 % ] ) patients , doxycycline 4/12 ( 33.3 % [ 6.6 - 59.9 % ] ) , and chloroquine 5/17 ( 29.4 % [ 7.7 - 51.1 % ] ) . Chloroquine/doxycycline was effective against P. falciparum but only modestly effective against P. vivax . These findings support the use of chloroquine/doxycycline as an inexpensive alternative to mefloquine for treating chloroquine-resistant P. falciparum but not chloroquine-resistant P. vivax in this setting Chloroquine remains the drug of choice for the treatment of vivax malaria in Thail and . Mixed infections of falciparum and vivax malaria are also common in South-East Asia . Laboratory confirmation of malaria species is not generally available . This study aim ed to find alternative regimens for treating both malaria species by using falciparum antimalarial drugs . From June 2004 to May 2005 , 98 patients with Plasmodium vivax were r and omly treated with either artemether-lumefantrine ( n = 47 ) or chloroquine ( n = 51 ) . Both treatments were followed by 15 mg of primaquine over 14 days . Adverse events and clinical and parasitological outcomes were recorded and revealed similar in both groups . The cure rate was 97.4 % for the artemether-lumefantrine treated group and 100 % for the chloroquine treated group . We concluded that the combination of artemether-lumefantrine and primaquine was well tolerated , as effective as chloroquine and primaquine , and can be an alternative regimen for treatment of vivax malaria especially in the event that a mixed infection of falciparum and vivax malaria could not be ruled out The blood stage antimalarial efficacy of primaquine ( 0.25 mg of base/kg of body weight/day over 14 days ) and chloroquine ( 25 mg of base/kg over 3 days ) were compared in 85 adult Thai men with acute Plasmodium vivax malaria . Most ( 75 % ) had at least one malaria episode previously . Parasite clearance times after primaquine alone ( n = 30 ) were slower than after chloroquine ( n = 30 ) or combined chloroquine-primaquine ( n = 25 ) , but all patients had a satisfactory initial therapeutic response . P. vivax malaria recurred in 10 ( 17 % ) of 60 patients followed for > or = 2 months and Plasmodium falciparum malaria developed in another 5 ( 8 % ) without reexposure to infection . Recurrences occurred < or = 5 weeks after primaquine treatment ( n = 4 ) , suggesting recrudescence , whereas recurrences after chloroquine treatment ( n = 6 ) occurred > or = 5 weeks later , suggesting relapse . Vivax malaria responds well initially to either primaquine or chloroquine . The blood stage antimalarial activity of primaquine may mask chloroquine resistance in combined regimens INTRODUCTION The decrease in the efficacy of antimalarial drugs in the world and in Colombia hampers its control . OBJECTIVE The in vivo therapeutic efficacy of the amodiaquine+sulfadoxine-pyrimethamine combination was evaluated in the treatment of uncomplicated Plasmodium falciparum malaria and of chloroquine for P. vivax malaria . MATERIAL S AND METHODS From May to November 2006 , in vivo efficacy studies of malaria treatments were undertaken in Tierralta , Córdoba , northeastern Colombia . St and ard protocol s were followed as recommended by the World Health Organization/Panamerican Health Organization , with some modifications . Patients older than two years with single P. falciparum or P. vivax infection , with asexual parasitemia between 500 and 50,000 parasites/microl , were selected according to established inclusion and exclusion criteria . Supervised treatment was administered , and clinical and parasitological follow-up was carried out on days 0 ( inclusion ) , 1 , 2 , 3 , 7 , 14 , 21 and 28 . The outcome was defined as adequate clinical and parasitological response , early therapeutic failure , or late therapeutic failure . RESULTS Of 53 subjects selected , 50 ( 94.3 % ; CI 70%-100 % ) presented adequate clinical and parasitological response to the amodiaquine+sulfadoxine-pyrimethamine treatment for uncomplicated falciparum malaria . One patient presented early therapeutic failure , and two developed late therapeutic failure . All of the 50 patients ( 95%CI : 74%-100 % ) in the invivo efficacy study of chloroquine for vivax malaria presented adequate clinical and parasitological response . CONCLUSION In Cordoba , the amodiaquine+sulfadoxine-pyrimethamine combination and chloroquine show a high efficacy for the treatment of uncomplicated falciparum and vivax malaria , respectively Chloroquine-resistant Plasmodium vivax has been the subject of numerous case reports and prospect i ve studies from Oceania and Asia . In contrast , only case reports exist from the Americas . We performed a prospect i ve study with 28-day follow-up of clinical responses to chloroquine in 2 P. vivax-endemic regions of Colombia . Three ( 11 % ) of 27 patients failed to respond to treatment with the st and ard regimen of chloroquine ( 1,500 mg of base over 3 days ) . One patient demonstrated RI resistance on Day 26 ; one patient demonstrated RI resistance due to recrudescence of blood stages on Day 11 ; and one patient demonstrated RII resistance of blood stages by never displaying clearing of peripheral parasitemia . All patients were successfully treated with primaquine , which has some blood stage efficacy against P. vivax , combined with a second course of chloroquine . Clinical resistance of P. vivax to chloroquine is present in Colombia and should be monitored in the Americas This study was conducted during 2002 - 2004 at Mae Sot District , on the Thai-Myanmar border , an area of multidrug-resistant Plasmodium falciparum malaria . Sixty-two patients with P. vivax malaria were included in the study . All were r and omized into two groups to receive a 3-day regimen of chloroquine or a 3-day regimen of quinine . Primaquine was given to patients in both groups for the elimination of hepatic stages . Results from the present study suggest that the st and ard regimen of chloroquine and a 3-day course of quinine at the dose regimens under investigation were very effective and well tolerated for the treatment of P. vivax malaria in this area . All patients responded well to both drug regimens ; the cure rates with chloroquine or quinine , when given concurrently with the tissue schizontocidal drug primaquine , were virtually 100 % within 28 days of follow-up . No significant correlations between parasite clearance time ( PCT ) or fever clearance time ( FCT ) and inhibitory concentration 50 ( IC50 ) were found . Patients who had PCT < or = 24 h and those with PCT > 24 h had comparable IC50 to chloroquine ( alone and plus primaquine ) and quinine , as well as similar concentrations of chloroquine/desethylchloroquine ( in blood ) or quinine ( in plasma ) at the investigated time points BACKGROUND Clinical effectiveness of previous regimens to treat Plasmodium vivax infection have been hampered by compliance . We aim ed to assess the dose-response , safety , and tolerability of single-dose tafenoquine plus 3-day chloroquine for P vivax malaria radical cure . METHODS In this double-blind , r and omised , dose-ranging phase 2b study , men and women ( aged ≥16 years ) with microscopically confirmed P vivax monoinfection ( parasite density > 100 to < 100,000 per μL blood ) were enrolled from community health centres and hospitals across seven sites in Brazil , Peru , India , and Thail and . Patients with glucose-6-phosphate dehydrogenase enzyme activity of less than 70 % were excluded . Eligible patients received chloroquine ( days 1 - 3 ) and were r and omly assigned ( 1:1:1:1:1:1 ) by a computer-generated r and omisation schedule to receive single-dose tafenoquine 50 mg , 100 mg , 300 mg , or 600 mg , primaquine 15 mg for 14 days , or chloroquine alone . R and omisation was stratified by baseline parasite count ( ≤7500 and > 7500 per μL blood ) . The primary efficacy endpoint was relapse-free efficacy at 6 months from initial dose ( ie , clearance of initial infection without subsequent microscopically confirmed infection ) , analysed by intention to treat . This study is registered with Clinical Trials.gov , number NCT01376167 . FINDINGS Between Sept 19 , 2011 , and March 25 , 2013 , 329 patients were r and omly assigned to a treatment group ( chloroquine plus tafenoquine 50 mg [ n=55 ] , 100 mg [ n=57 ] , 300 mg [ n=57 ] , 600 mg [ n=56 ] ; or to chloroquine plus primaquine [ n=50 ] ; or chloroquine alone [ n=54 ] ) . Relapse-free efficacy at 6 months was 57·7 % ( 95 % CI 43 - 70 ) with tafenoquine 50 mg , 54·1 % ( 40 - 66 ) with tafenoquine 100 mg , 89·2 % ( 77 - 95 ) with tafenoquine 300 mg , 91·9 % ( 80 - 97 ) with tafenoquine 600 mg , 77·3 % ( 63 - 87 ) with primaquine , and 37·5 % ( 23 - 52 ) with chloroquine alone . Tafenoquine 300 mg and 600 mg had better efficacy than chloroquine alone ( treatment differences 51·7 % [ 95 % CI 35 - 69 ] , p<0·0001 , with tafenoquine 300 mg and 54·5 % [ 38 - 71 ] , p<0·0001 , with tafenoquine 600 mg ) , as did primaquine ( treatment difference 39·9 % [ 21 - 59 ] , p=0·0004 ) . Adverse events were similar between treatments . 29 serious adverse events occurred in 26 ( 8 % ) of 329 patients ; QT prolongation was the most common serious adverse event ( 11 [ 3 % ] of 329 ) , occurring in five ( 2 % ) of 225 patients receiving tafenoquine , four ( 8 % ) of 50 patients receiving primaquine , and two ( 4 % ) of 54 patients receiving chloroquine alone , with no evidence of an additional effect on QT of chloroquine plus tafenoquine coadministration . INTERPRETATION Single-dose tafenoquine 300 mg coadministered with chloroquine for P vivax malaria relapse prevention was more efficacious than chloroquine alone , with a similar safety profile . As a result , it has been selected for further clinical assessment in phase 3 . FUNDING GlaxoSmithKline , Medicines for Malaria Venture |
13,817 | 31,489,131 | Preliminary evidence suggests that exercise and cortisol administration may have an adjuvant effect on PTSD symptom reduction .
Breathing biofeedback showed a trend for an adjuvant effect and an effect for accelerated symptom reduction .
Conclusions : Currently , it is not possible to formulate evidence -based clinical recommendations regarding adjuvants interventions . | ABSTRACT Background : According to clinical guidelines , trauma-focused psychotherapies ( TF-PT ) such as trauma-focused cognitive behavioural therapy ( TF-CBT ) and eye movement desensitization and reprocessing ( EMDR ) are recommended as first-line treatments for posttraumatic stress disorder ( PTSD ) .
TF-CBT and EMDR are equally effective and have large effect sizes .
However , many patients fail to respond or have comorbid symptoms or disorders that only partially decline with TF-PT .
Thus , there is growing interest in augmenting TF-PT through adjuvant interventions .
Objective : The current systematic review aims to assess whether adjuvant interventions improve outcome among adult PTSD patients receiving TF-PT . | This study tested a family-based skills-building intervention in veterans with chronic combat-related posttraumatic stress disorder ( PTSD ) . Veterans and a family member were r and omly assigned to 1 of 3 conditions : ( a ) waiting list , ( b ) 18 sessions of twice-weekly exposure therapy , or ( c ) 18 sessions of twice-weekly exposure therapy followed by 16 sessions of behavioral family therapy ( BFT ) . Participation in exposure therapy reduced PTSD positive symptoms ( e.g. , reexperiencing and hyperarousal ) but not PTSD negative symptoms . Positive symptom gains were maintained at 6-month follow-up . However , participation in BFT had no additional impact on PTSD symptoms OBJECTIVE The memory-enhancing drug methylene blue ( MB ) administered after extinction training improves fear extinction retention in rats and humans with claustrophobia . Robust findings from animal research , in combination with established safety and data showing MB-enhanced extinction in humans , provide a foundation to extend this work to extinction-based therapies for posttraumatic stress disorder ( PTSD ) such as prolonged exposure ( PE ) . METHODS Patients with chronic PTSD ( DSM-IV-TR ; N = 42 ) were r and omly assigned to imaginal exposure plus MB ( IE + MB ) , imaginal exposure plus placebo ( IE + PBO ) , or waitlist ( WL/st and ard PE ) from September 2011 to April 2013 . Following 5 daily , 50-minute imaginal exposure sessions , 260 mg of MB or PBO was administered . Waitlist controls received PE following 1-month follow-up . Patients were assessed using the independent evaluator-rated PTSD Symptom Scale-Interview version ( primary outcome ) , patient-rated PTSD , trauma-related psychopathology , and functioning through 3-month follow-up . RESULTS Both IE + MB and IE + PBO showed strong clinical gains that did not differ from st and ard PE at 3-month follow-up . MB-augmented exposure specifically enhanced independent evaluator-rated treatment response ( number needed to treat = 7.5 ) and quality of life compared to placebo ( effect size d = 0.58 ) . Rate of change for IE + MB showed a delayed initial response followed by accelerated recovery , which differed from the linear pattern seen in IE + PBO . MB effects were facilitated by better working memory but not by changes in beliefs . CONCLUSIONS The findings provide preliminary efficacy for a brief IE treatment for PTSD and point to the potential utility of MB for enhancing outcome . Brief interventions and better tailoring of MB augmentation strategies , adjusting for observed patterns , may have the potential to reduce dropout , accelerate change , and improve outcomes . TRIAL REGISTRATION Clinical Trials.gov identifier : NCT01188694 Abstract This r and omized controlled trial was design ed to determine if art therapy in conjunction with Cognitive Processing Therapy ( CPT ) was more effective for reducing symptoms of combat posttraumatic stress disorder ( PTSD ) than CPT alone . Veterans ( N = 11 ) were r and omized to receive either individual CPT , or individual CPT in conjunction with individual art therapy . PTSD Checklist – Military Version and Beck Depression Inventory – II scores improved with treatment in both groups with no significant difference in improvement between the experimental and control groups . Art therapy in conjunction with CPT was found to improve trauma processing and veterans considered it to be an important part of their treatment as it provided healthy distancing , enhanced trauma recall , and increased access to emotions BACKGROUND Posttraumatic stress disorder ( PTSD ) is prevalent among military veterans and is associated with significant negative health outcomes . However , stigma and other barriers to care prevent many veterans from pursuing traditional mental health treatment . We developed a group-based Integrative Exercise ( IE ) program combining aerobic and resistance exercise , which is familiar to veterans , with mindfulness-based practice s suited to veterans with PTSD . This study aim ed to evaluate the effects of IE on PTSD symptom severity and quality of life , as well as assess the feasibility and acceptability of IE . METHODS Veterans ( N = 47 ) were r and omized to either IE or waitlist control ( WL ) . Veterans in IE were asked to attend three 1-h group exercise sessions for 12 weeks . RESULTS Compared with WL , veterans r and omized to IE demonstrated a greater reduction in PTSD symptom severity ( d = -.90 ) , a greater improvement in psychological quality of life ( d = .53 ) and a smaller relative improvement in physical quality of life ( d = .30 ) Veterans ' ratings of IE indicated high feasibility and acceptability . LIMITATIONS The sample was relatively small and recruited from one site . The comparison condition was an inactive control . CONCLUSIONS This initial study suggests that IE is an innovative approach to treating veterans with symptoms of PTSD that reduces symptoms of posttraumatic stress and improves psychological quality of life . This approach to recovery may exp and the reach of PTSD treatment into non-traditional setting s and to veterans who may prefer a familiar activity , such as exercise , over medication or psychotherapy Rationale To improve outcomes for patients undergoing extinction-based therapies ( e.g. , exposure therapy ) for anxiety disorders such as post-traumatic stress disorder ( PTSD ) , there has been interest in identifying pharmaceutical compounds that might facilitate fear extinction learning and recall . Oxytocin ( OT ) is a mammalian neuropeptide that modulates activation of fear extinction-based neural circuits and fear responses . Little is known , however , about the effects of OT treatment on conditioned fear responding and extinction in humans . Objectives The purpose of the present study was to assess the effects of OT in a fear-potentiated startle task of fear conditioning and extinction . Methods A double-blind , placebo-controlled study of 44 healthy human participants was conducted . Participants underwent a conditioned fear acquisition procedure , after which they were r and omized to treatment group and delivered OT ( 24 IU ) or placebo via intranasal ( IN ) spray . Forty-five minutes after treatment , participants underwent extinction training . Twenty-four hours later , subjects were tested for extinction recall . Results Relative to placebo , the OT group showed increased fear-potentiated startle responding during the earliest stage of extinction training relative to placebo ; however , all treatment groups showed the same level of reduced responding by the end of extinction training . Twenty-four hours later , the OT group showed significantly higher recall of extinction relative to placebo . Conclusions The current study provides preliminary evidence that OT may facilitate fear extinction recall in humans . These results support further study of OT as a potential adjunctive treatment for extinction-based therapies in fear-related disorders OBJECTIVE The authors examined the effectiveness of virtual reality exposure augmented with D-cycloserine or alprazolam , compared with placebo , in reducing posttraumatic stress disorder ( PTSD ) due to military trauma . METHOD After an introductory session , five sessions of virtual reality exposure were augmented with D-cycloserine ( 50 mg ) or alprazolam ( 0.25 mg ) in a double-blind , placebo-controlled r and omized clinical trial for 156 Iraq and Afghanistan war veterans with PTSD . RESULTS PTSD symptoms significantly improved from pre- to posttreatment across all conditions and were maintained at 3 , 6 , and 12 months . There were no overall differences in symptoms between D-cycloserine and placebo at any time . Alprazolam and placebo differed significantly on the Clinician-Administered PTSD Scale score at posttreatment and PTSD diagnosis at 3 months posttreatment ; the alprazolam group showed a higher rate of PTSD ( 82.8 % ) than the placebo group ( 47.8 % ) . Between-session extinction learning was a treatment-specific enhancer of outcome for the D-cycloserine group only . At posttreatment , the D-cycloserine group had the lowest cortisol reactivity and smallest startle response during virtual reality scenes . CONCLUSIONS A six-session virtual reality treatment was associated with reduction in PTSD diagnoses and symptoms in Iraq and Afghanistan veterans , although there was no control condition for the virtual reality exposure . There was no advantage of D-cycloserine for PTSD symptoms in primary analyses . In secondary analyses , alprazolam impaired recovery and D-cycloserine enhanced virtual reality outcome in patients who demonstrated within-session learning . D-cycloserine augmentation reduced cortisol and startle reactivity more than did alprazolam or placebo , findings that are consistent with those in the animal literature Abstract Although trauma-focused cognitive behavioral therapy ( TF-CBT ) with exposure is an effective treatment for posttraumatic stress disorder ( PTSD ) , not all patients recover . Addition of breathing biofeedback to exposure in TF-CBT is suggested as a promising complementary technique to improve recovery of PTSD symptoms . Patients ( n = 8) with chronic PTSD were r and omized to regular TF-CBT or TF-CBT with complementary breathing biofeedback to exposure . PTSD symptoms were measured before , during and after TF-CBT with the Impact of Event Scale-Revised . The results show that breathing biofeedback is feasible and can easily be complemented to TF-CBT . Although PTSD symptoms significantly decreased from pre to post treatment in both conditions , there was a clear trend towards a significantly faster ( p = .051 ) symptom reduction in biofeedback compared to regular TF-CBT . The most important limitation was the small sample size . The hastened clinical improvement in the biofeedback condition supports the idea that breathing biofeedback may be an effective complementary component to exposure in PTSD patients . The mechanism of action of breathing biofeedback may relate to competing working memory re sources decreasing vividness and emotionality , similar to eye movement desensitization and reprocessing . Future research is needed to examine this Exposure to combat experiences is associated with increased risk of developing Post Traumatic Stress Disorder . Prolonged exposure therapy and cognitive processing therapy have garnered a significant amount of empirical support for PTSD treatment ; however , they are not universally effective with some patients continuing to struggle with residual PTSD symptoms . Heart rate variability ( HRV ) is a measure of the autonomic nervous system functioning and reflects an individual ’s ability to adaptively cope with stress . A pilot study was undertaken to determine if veterans with PTSD ( as measured by the Clinician-Administered PTSD Scale and the PTSD Checklist ) would show significantly different HRV prior to an intervention at baseline compared to controls ; specifically , to determine whether the HRV among veterans with PTSD is more depressed than that among veterans without PTSD . The study also aim ed at assessing the feasibility , acceptability , and potential efficacy of providing HRV biofeedback as a treatment for PTSD . The findings suggest that implementing an HRV biofeedback as a treatment for PTSD is effective , feasible , and acceptable for veterans . Veterans with combat-related PTSD displayed significantly depressed HRV as compared to subjects without PTSD . When the veterans with PTSD were r and omly assigned to receive either HRV biofeedback plus treatment as usual ( TAU ) or just TAU , the results indicated that HRV biofeedback significantly increased the HRV while reducing symptoms of PTSD . However , the TAU had no significant effect on either HRV or symptom reduction . A larger r and omized control trial to vali date these findings appears warranted Behavioral exposure therapy of anxiety disorders is believed to rely on fear extinction . Because pre clinical studies have shown that glucocorticoids can promote extinction processes , we aim ed at investigating whether the administration of these hormones might be useful in enhancing exposure therapy . In a r and omized , double-blind , placebo-controlled study , 40 patients with specific phobia for heights were treated with three sessions of exposure therapy using virtual reality exposure to heights . Cortisol ( 20 mg ) or placebo was administered orally 1 h before each of the treatment sessions . Subjects returned for a posttreatment assessment 3–5 d after the last treatment session and for a follow-up assessment after 1 mo . Adding cortisol to exposure therapy result ed in a significantly greater reduction in fear of heights as measured with the acrophobia question naire ( AQ ) both at posttreatment and at follow-up , compared with placebo . Furthermore , subjects receiving cortisol showed a significantly greater reduction in acute anxiety during virtual exposure to a phobic situation at posttreatment and a significantly smaller exposure-induced increase in skin conductance level at follow-up . The present findings indicate that the administration of cortisol can enhance extinction-based psychotherapy OBJECTIVE Despite the success of empirically supported treatments for posttraumatic stress disorder ( PTSD ) , sleep impairment frequently remains refractory after treatment . This single-site , r and omized controlled trial examined the effectiveness of sleep-directed hypnosis as a complement to an empirically supported psychotherapy for PTSD ( cognitive processing therapy [ CPT ] ) . METHOD Participants completed either 3 weeks of hypnosis ( n = 52 ) or a symptom monitoring control condition ( n = 56 ) before beginning st and ard CPT . Multilevel modeling was used to investigate differential patterns of change to determine whether hypnosis result ed in improvements in sleep , PTSD , and depression . An intervening variable approach was then used to determine whether improvements in sleep achieved during hypnosis augmented change in PTSD and depression during CPT . RESULTS After the initial phase of treatment ( hypnosis or symptom monitoring ) , the hypnosis condition showed significantly greater improvement than the control condition in sleep and depression , but not PTSD . After CPT , both conditions demonstrated significant improvement in sleep and PTSD ; however , the hypnosis condition demonstrated greater improvement in depressive symptoms . As sleep improved , there were corresponding improvements in PTSD and depression , with a stronger relationship between sleep and PTSD . CONCLUSION Hypnosis was effective in improving sleep impairment , but those improvements did not augment gains in PTSD recovery during the trauma-focused intervention . ( PsycINFO Data base OBJECTIVE Pre clinical studies have shown that low-dose methylene blue increases mitochondrial cytochrome oxidase activity in the brain and improves memory retention after learning tasks , including fear extinction . The authors report on the first controlled experiment to examine the memory-enhancing effects of posttraining methylene blue administration on retention of fear extinction and context ual memory following fear extinction training . METHOD Adult participants displaying marked claustrophobic fear were r and omly assigned to double-blind administration of 260 mg of methylene blue ( N=23 ) or administration of placebo ( N=19 ) immediately following six 5-minute extinction trials in an enclosed chamber . Retesting occurred 1 month later to assess fear renewal as indexed by peak fear during exposure to a nontraining chamber , with the prediction that the effects of methylene blue would vary as a function of fear reduction achieved during extinction training . Incidental context ual memory was assessed 1 and 30 days after training to assess the cognitive-enhancing effects of methylene blue independent of its effects on fear attenuation . RESULTS Consistent with predictions , participants displaying low end fear posttraining showed significantly less fear at the 1-month follow-up if they received methylene blue posttraining compared with placebo . In contrast , participants displaying moderate to high levels of posttraining fear tended to fare worse at the follow-up if they received methylene blue posttraining . Methylene blue 's enhancement of context ual memory was unrelated to initial or posttraining claustrophobic fear . CONCLUSIONS Methylene blue enhances memory and the retention of fear extinction when administered after a successful exposure session but may have a deleterious effect on extinction when administered after an unsuccessful exposure session Background : Initial posttraumatic stress disorder ( PTSD ) care is often delayed and many with PTSD go untreated . Acupuncture appears to be a safe , potentially nonstigmatizing treatment that reduces symptoms of anxiety , depression , and chronic pain , but little is known about its effect on PTSD . Methods : Fifty-five service members meeting research diagnostic criteria for PTSD were r and omized to usual PTSD care ( UPC ) plus eight 60-minute sessions of acupuncture conducted twice weekly or to UPC alone . Outcomes were assessed at baseline and 4 , 8 , and 12 weeks postr and omization . The primary study outcomes were difference in PTSD symptom improvement on the PTSD Checklist ( PCL ) and the Clinician-administered PTSD Scale ( CAPS ) from baseline to 12-week follow-up between the 2 treatment groups . Secondary outcomes were depression , pain severity , and mental and physical health functioning . Mixed model regression and t test analyses were applied to the data . Results : Mean improvement in PTSD severity was significantly greater among those receiving acupuncture than in those receiving UPC ( PCL&Dgr;=19.8±13.3 vs. 9.7±12.9 , P<0.001 ; CAPS&Dgr;=35.0±20.26 vs. 10.9±20.8 , P<0.0001 ) . Acupuncture was also associated with significantly greater improvements in depression , pain , and physical and mental health functioning . Pre-post effect-sizes for these outcomes were large and robust . Conclusions : Acupuncture was effective for reducing PTSD symptoms . Limitations included small sample size and inability to parse specific treatment mechanisms . Larger multisite trials with longer follow-up , comparisons to st and ard PTSD treatments , and assessment s of treatment acceptability are needed . Acupuncture is a novel therapeutic option that may help to improve population reach of PTSD treatment Posttraumatic stress disorder ( PTSD ) is a chronic , debilitating condition for which Prolonged Exposure ( PE ) therapy is highly efficacious . However , for some individuals , premature dropout and residual PTSD symptoms remain obstacles . The neuropeptide oxytocin is a promising c and i date to enhance PE due to its ability to enhance 1 ) prosocial cognition and behavior , which are theorized to promote positive working alliance , and 2 ) extinction learning , which is the central mechanism of action underlying successful PE treatment . Despite a robust theoretical rationale , no studies to date have combined evidence -based psychotherapy for PTSD with oxytocin . This r and omized , placebo-controlled , double-blind pilot trial examined the feasibility , safety , and preliminary efficacy of augmenting PE with oxytocin . Participants were 17 individuals with diverse index traumas . Participants self-administered intranasal oxytocin ( 40 IU ) or matching placebo 45 min prior to each weekly PE therapy session . One adverse event occurred in the placebo group and three individuals dropped out ( 17.6 % ; 2 oxytocin group and 1 placebo group ) . The oxytocin group demonstrated lower PTSD and depression symptoms during PE , and had higher working alliance scores , although these differences did not reach statistical significance . Although preliminary , the findings support the feasibility of oxytocin combined with PE . Adequately powered studies are necessary to determine whether oxytocin enhances PE treatment outcomes and to examine potential mechanisms , such as accelerating extinction learning , enhancing early response , and preventing premature dropout . NCT03238924 Abstract EEG Biofeedback ( also known as neurofeedback ) has been in use as a clinical intervention for well over 30 years ; however , it has made very little impact on clinical care . One reason for this has been the difficulty in design ing research to measure clinical change in the real world . While substantial evidence exists for its efficacy in treating attention deficit/hyperactivity disorder , relatively little evidence exists for its utility in other disorders including posttraumatic stress disorder ( PTSD ) . The current study represents a “ proof-of-concept ” pilot for the use of neurofeedback with multiply-traumatized individuals with treatment-resistant PTSD . Participants completed 40 sessions of neurofeedback training two times per week with sensors r and omly assigned ( by the study coordinator , who was not blind to condition ) to sensor placements of either T4-P4 or T3-T4 . We found that neurofeedback significantly reduced PTSD symptoms ( Davidson Trauma Scale scores averaged 69.14 at baseline to 49.26 at termination ) , and preceded gains in affect regulation ( Inventory of Altered Self-Capacities-Affect Dysregulation scores averaged 23.63 at baseline to 17.20 at termination ) . We discuss a roadmap for future research Previous research in patients with phobia showed that the administration of glucocorticoids reduces fear in phobic situations and enhances exposure therapy . Glucocorticoids underlie a daily cycle with a peak in the morning and low levels during the evening and night . The aim of the present study was to investigate whether exposure is more effective when conducted in the morning when endogenous cortisol levels are high . Sixty patients meeting DSM IV criteria for specific phobia ( animal type ) were r and omly assigned to one-session exposure treatment either at 08.00 a.m. ( high cortisol group ) or at 06.00 p.m. ( low cortisol group ) . Participants returned for a posttreatment assessment one week after therapy and a follow-up assessment three months after therapy . Both groups showed good outcome , but patients treated in the morning exhibited significantly less fear of spiders in the behavioral approach test ( BAT ) and a trend for lower scores on the Fear of Spiders Question naire ( FSQ ) than patients treated in the evening . This effect was present at posttreatment and follow-up . Our findings indicate that exposure therapy is more effective in the morning than in the evening . We suggest that this may be due to higher endogenous cortisol levels in the morning group that enhance extinction memory The paper describes the development of a cognitive therapy ( CT ) program for post-traumatic stress disorder ( PTSD ) that is based on a recent cognitive model ( Behav . Res . Therapy 38 ( 2000 ) 319 ) . In a consecutive case series , 20 PTSD patients treated with CT showed highly significant improvement in symptoms of PTSD , depression and anxiety . A subsequent r and omized controlled trial compared CT ( N = 14 ) and a 3-month waitlist condition ( WL , N = 14 ) . CT led to large reductions in PTSD symptoms , disability , depression and anxiety , whereas the waitlist group did not improve . In both studies , treatment gains were well maintained at 6-month follow-up . CT was highly acceptable , with an overall dropout rate of only 3 % . The intent-to-treat effect sizes for the degree of change in PTSD symptoms from pre to post-treatment were 2.70 - 2.82 ( self-report ) , and 2.07 ( assessor-rated ) . The controlled effect sizes for CT versus WL post-treatment scores were 2.25 ( self-report ) and 2.18 ( assessor-rated ) . As predicted by the cognitive model , good treatment outcome was related to greater changes in dysfunctional post-traumatic cognitions . Patient characteristics such as comorbidity , type of trauma , history of previous trauma , or time since the traumatic event did not predict treatment response , however , low educational attainment and low socioeconomic status were related to better outcome D-Cycloserine ( DCS ) is a partial NMDA receptor agonist that has been shown to enhance therapeutic response to exposure-based treatments for anxiety disorders , but has not been tested in the treatment of combat-related posttraumatic stress disorder ( PTSD ) . The aim of this r and omized , double-blind , placebo-controlled trial was to determine whether DCS augments exposure therapy for PTSD in veterans returning from Iraq and Afghanistan and to test whether a brief six-session course of exposure therapy could effectively reduce PTSD symptoms in returning veterans . In contrast to previous trials using DCS to enhance exposure therapy , results indicated that veterans in the exposure therapy plus DCS condition experienced significantly less symptom reduction than those in the exposure therapy plus placebo condition over the course of the treatment . Possible reasons for why DCS was associated with poorer outcome are discussed . Clinical trials.gov Registry # : NCT00371176 ; A Placebo-Controlled Trail of D-Cycloserine and Exposure Therapy for Combat-PTSD ; www . clinical trials.gov/ct2/ results ? term = NCT00371176 BACKGROUND Posttraumatic stress disorder ( PTSD ) is a complex and debilitating anxiety disorder , and , although prolonged exposure therapy has been proven effective , many patients remain symptomatic after treatment . In other anxiety disorders , the supplementary use of D-cycloserine ( DCS ) , a partial agonist at the glutamatergic N-methyl-D-aspartate receptor , showed promise in enhancing treatment effects . We examined whether augmentation of prolonged exposure therapy for PTSD with DCS enhances treatment efficacy . METHODS In a r and omized , double-blind , placebo-controlled trial we administered 50 mg DCS or placebo 1 hour before each exposure session to 67 mixed trauma patients , recruited from regular referrals , with a primary PTSD diagnosis satisfying DSM-IV criteria . RESULTS Although DCS did not enhance overall treatment effects , the participants having received DCS did show a stronger treatment response . Exploratory session-by-session analyses revealed that DCS yielded higher symptom reduction in those participants that had more severe pretreatment PTSD and needed longer treatment . CONCLUSIONS The present study found preliminary support for the augmentation of exposure therapy with DCS , specifically for patients with more severe PTSD needing longer treatment BACKGROUND Prolonged exposure ( PE ) therapy for post-traumatic stress disorder ( PTSD ) in military veterans has established efficacy , but is ineffective for a substantial number of patients . PE is also associated with high dropout rates . We hypothesized that hydrocortisone augmentation would enhance symptom improvement and reduce drop-out rates by diminishing the distressing effects of traumatic memories retrieved during imaginal exposure . We also hypothesized that in responders , hydrocortisone augmentation would be more effective in reversing glucocorticoid indices associated with PTSD than placebo augmentation . METHOD Twenty-four veterans were r and omized to receive either 30 mg oral hydrocortisone or placebo prior to PE sessions 3 - 10 in a double-blind protocol . Glucocorticoid receptor sensitivity was assessed in cultured peripheral blood mononuclear cells ( P BMC ) using the in vitro lysozyme inhibition test and was determined before and after treatment . Intent-to-treat analysis was performed using latent growth curve modeling of treatment effects on change in PTSD severity over time . Veterans who no longer met diagnostic criteria for PTSD at post-treatment were design ated as responders . RESULTS Veterans r and omized to hydrocortisone or placebo augmentation did not differ significantly in clinical severity or glucocorticoid sensitivity at pre-treatment . Hydrocortisone augmentation was associated with greater reduction in total PTSD symptoms compared to placebo , a finding that was explained by significantly greater patient retention in the hydrocortisone augmentation condition . A significant treatment condition by responder status interaction for glucocorticoid sensitivity indicated that responders to hydrocortisone augmentation had the highest pre-treatment glucocorticoid sensitivity ( lowest lysozyme IC50-DEX ) that diminished over the course of treatment . There was a significant association between decline in glucocorticoid responsiveness and improvement in PTSD symptoms among hydrocortisone recipients . CONCLUSIONS The results of this pilot study suggest that hydrocortisone augmentation of PE may result in greater retention in treatment and thereby promote PTSD symptom improvement . Further , the results suggest that particularly elevated glucocorticoid responsiveness at pre-treatment may identify veterans likely to respond to PE combined with an intervention that targets glucocorticoid sensitivity . Confirmation of these findings will suggest that pharmacologic interventions that target PTSD-associated glucocorticoid dysregulation may be particularly helpful in promoting a positive clinical response to PTSD psychotherapy Viewing post-traumatic stress disorder ( PTSD ) as a disorder of emotional learning , this study used a cognitive enhancer synergistically with virtual reality exposure ( VRE ) therapy for the treatment of PTSD . The main objective was to determine if a novel pharmacotherapy , D-cycloserine ( DCS ) , enhanced the efficacy of the psychotherapy . Pre- clinical studies suggest that when fear extinction occurs during DCS administration , neuroplasticity may be enhanced . VRE therapy is a particularly promising format to test the hypothesis that DCS enhances extinction learning , as sensory fear cues are st and ardized across patients . In a pilot r and omized , double-blind , placebo-controlled trial , 100 mg of DCS or placebo was administered 90 min before each weekly VRE session , to ensure peak plasma concentrations during the sessions in 25 patients with chronic PTSD . The primary outcome measure was the Clinician Administered PTSD Scale ( CAPS ) . Secondary outcome measures included the Beck Depression Inventory-II and the State-Trait Anger Expression Inventory-2 . Assessment s occurred at pre-treatment , following sessions 3 , 6 , 10 , post-treatment , and at 6 months . The difference in CAPS between the VRE-DCS ( n=13 ) and VRE-placebo ( n=12 ) groups increased over time beginning at 6 weeks , with medium to large between-group effect sizes immediately post-treatment and 6 months later ( d=0.68 and d=1.13 , respectively ) . A similar pattern was observed for depression , anger expression , and sleep . PTSD remission rates were significantly greater for the VRE-DCS group ( 46 % vs 8 % at post-treatment ; 69 % vs 17 % at 6 months ) . Patients in the VRE-DCS group showed earlier and greater improvement in PTSD symptoms compared with the VRE-placebo group . These results suggest a promising new treatment for PTSD Evidence suggests aerobic exercise has anxiolytic effects ; yet , the treatment potential for posttraumatic stress disorder ( PTSD ) and responsible anxiolytic mechanisms have received little attention . Emerging evidence indicates that attentional focus during exercise may dictate the extent of therapeutic benefit . Whether benefits are a function of attentional focus toward or away from somatic arousal during exercise remains untested . Thirty-three PTSD-affected participants completed two weeks of stationary biking aerobic exercise ( six sessions ) . To assess the effect of attentional focus , participants were r and omized into three exercise groups : group 1 ( attention to somatic arousal ) received prompts directing their attention to the interoceptive effects of exercise , group 2 ( distraction from somatic arousal ) watched a nature documentary , and group 3 exercised with no distractions or interoceptive prompts . Hierarchal linear modeling showed all groups reported reduced PTSD and anxiety sensitivity ( AS ; i.e. , fear of arousal-related somatic sensations ) during treatment . Interaction effects between group and time were found for PTSD hyperarousal and AS physical and social scores , wherein group 1 , receiving interoceptive prompts , experienced significantly less symptom reduction than other groups . Most participants ( 89 % ) reported clinical ly significant reductions in PTSD severity after the two-week intervention . Findings suggest , regardless of attentional focus , aerobic exercise reduces PTSD symptoms Brain-derived neurotrophic factor ( BDNF ) is associated with synaptic plasticity , which is crucial for long-term learning and memory . Some studies suggest that people suffering from anxiety disorders show reduced BDNF relative to healthy controls . Lower BDNF is associated with impaired learning , cognitive deficits , and poor exposure-based treatment outcomes . A series of studies with rats showed that exercise elevates BDNF and enhances fear extinction . However , this strategy has not been tested in humans . In this pilot study , we r and omized participants ( N = 9 , 8 females , MAge = 34 ) with posttraumatic stress disorder ( PTSD ) to ( a ) prolonged exposure alone ( PE ) or ( b ) prolonged exposure+exercise ( PE+E ) . Participants r and omized to the PE+E condition completed a 30-minute bout of moderate-intensity treadmill exercise ( 70 % of age-predicted HRmax ) prior to each PE session . Consistent with prediction , the PE+E group showed a greater improvement in PTSD symptoms ( d = 2.65 ) and elevated BDNF ( d = 1.08 ) relative to the PE only condition . This pilot study provides initial support for further investigation into exercise augmented exposure therapy BACKGROUND Pre clinical and clinical studies indicate that the administration of glucocorticoids may promote fear extinction processes . In particular , it has been shown that glucocorticoids enhance virtual reality based exposure therapy of fear of heights . Here , we investigate whether glucocorticoids enhance the outcome of in vivo exposure-based group therapy of spider phobia . METHODS In a double blind , block-r and omized , placebo-controlled , between-subject study design , 22 patients with specific phobia of spiders were treated with two sessions of in vivo exposure-based group therapy . Cortisol ( 20 mg ) or placebo was orally administered 1 hr before each therapy session . Patients returned for a follow-up assessment one month after therapy . RESULTS Exposure-based group therapy led to a significant decrease in phobic symptoms as assessed with the Fear of Spiders Question naire ( FSQ ) from pretreatment to immediate posttreatment and to follow-up . The administration of cortisol to exposure therapy result ed in increased salivary cortisol concentrations and a significantly greater reduction in fear of spiders ( FSQ ) as compared to placebo at follow-up , but not immediately posttreatment . Furthermore , cortisol-treated patients reported significantly less anxiety during st and ardized exposure to living spiders at follow-up than placebo-treated subjects . Notably , groups did not differ in phobia-unrelated state-anxiety before and after the exposure sessions and at follow-up . CONCLUSIONS These findings indicate that adding cortisol to in vivo exposure-based group therapy of spider phobia enhances treatment outcome Abstract The alpha-2 adrenergic receptor antagonist , yohimbine , can facilitate fear extinction in animals and humans . One potential mechanism is increased noradrenergic activity and associated arousal in the presence of conditioned stimuli . Accordingly , yohimbine might augment prolonged exposure ( PE ) therapy for posttraumatic stress disorder ( PTSD ) , where heightened exposure-oriented arousal is a theorized driver and empirical predictor of treatment success . A double-blind placebo-controlled r and omized trial ( NCT 01031979 ) piloted yohimbine augmentation in 26 males with combat-related PTSD . Participants were given one-time dose of yohimbine or placebo prior to the first imaginal exposure . Subsequently , both arms completed st and ard PE . The primary outcome was trauma-cued heart-rate reactivity a week after the drug/exposure visit , a highly specified , objective measure sensitive to incremental change . Secondary outcomes included arousal during the drug/exposure visit and slope of distress , PTSD , and depression over the course of PE . Consistent with hypothesis , yohimbine led to higher objective and subjective arousal during the drug/exposure visit and to lower trauma-cued heart-rate reactivity one-week later . One dose of yohimbine also led to greater between-session habituation and more rapid improvement on depression , but not PTSD , over the course of care . Results of this controlled pilot indicate support for continued investigation of yohimbine-augmented exposure therapy for PTSD |
13,818 | 22,895,969 | At present , there is insufficient evidence to determine whether curative treatment of genital ulcer disease would reduce the risk of HIV acquisition .
The very low quality of the evidence implies that the true effect of genital ulcer disease treatment on sexual acquisition of HIV may be substantially different from the effect estimated from currently available data . | BACKGROUND Genital ulcer disease by virtue of disruption of the mucosal surfaces may enhance HIV acquisition .
Genital ulcer disease treatment with resolution of the ulcers may therefore contribute in reducing the sexual acquisition of HIV .
OBJECTIVES To determine the effects of treatment of genital ulcer disease on sexual acquisition of HIV . | A r and omized cross-over trial of herpes simplex virus type 2 (HSV-2)-suppressive therapy ( valacyclovir , 500 mg twice daily , or placebo for 8 weeks , a 2-week washout period , then the alternative therapy for 8 weeks ) was conducted among 20 Peruvian women coinfected with HSV-2 and human immunodeficiency virus type 1 ( HIV-1 ) who were not on antiretroviral therapy . Plasma sample s ( obtained weekly ) and endocervical swab specimens ( obtained thrice weekly ) were collected for HIV-1 RNA polymerase chain reaction . Plasma HIV-1 level was significantly lower during the valacyclovir arm , compared with the placebo arm ( -0.26 log10 copies/mL , a 45 % decrease [ P < .001 ] ) , as was cervical HIV-1 level ( -0.35 log10 copies/swab , a 55 % decrease [ P < .001 ] ) . Suppressive HSV-2 therapy has the potential to reduce HIV-1 infectiousness and slow HIV-1 disease progression A r and omised trial was done to evaluate the impact of improved sexually transmitted disease ( STD ) case management at primary health care level on the incidence of HIV infection in the rural Mwanza region of Tanzania . HIV incidence was compared in six intervention communities and six pair-matched comparison communities . A r and om cohort of about 1000 adults aged 15 - 54 years from each community was surveyed at baseline and at follow-up 2 years later . Intervention consisted of establishment of an STD reference clinic , staff training , regular supply of drugs , regular supervisory visits to health facilities , and health education about STDs . 12,537 individuals were recruited . Baseline HIV prevalences were 3.8 % and 4.4 % in the intervention and comparison communities , respectively . At follow-up , 8845 ( 71 % ) of the cohort were seen . Of those initially seronegative , the proportions seroconverting over 2 years were 48 of 4149 ( 1.2 % ) in the intervention communities and 82 of 4400 ( 1.9 % ) in the comparison communities . HIV incidence was consistently lower in the intervention communities in all six matched pairs . Allowing for the community-r and omised design and the effects of confounding factors , the estimated risk ratio was 0.58 ( 95 % CI 0.42 - 0.79 , p = 0.007 ) . No change in reported sexual behaviour was observed in either group . We conclude that improved STD treatment reduced HIV incidence by about 40 % in this rural population . This is the first r and omised trial to demonstrate an impact of a preventive intervention on HIV incidence in a general population Background Underst and ing the correlates of HIV shedding is important to inform strategies to reduce HIV infectiousness . We examined correlates of genital HIV-1 RNA in women who were seropositive for both herpes simplex virus (HSV)-2 and HIV-1 and who were enrolled in a r and omised controlled trial of HSV suppressive therapy ( aciclovir 400 mg b.i.d vs. placebo ) in Tanzania . Methodology Sample s , including a cervico-vaginal lavage , were collected and tested for genital HIV-1 and HSV and reproductive tract infections ( RTIs ) at r and omisation and 6 , 12 and 24 months follow-up . Data from all women at r and omisation and women in the placebo arm during follow-up were analysed using generalised estimating equations to determine the correlates of cervico-vaginal HIV-1 RNA detection and load . Principal Findings Cervico-vaginal HIV-1 RNA was detected at 52.0 % of 971 visits among 482 women , and was independently associated with plasma viral load , presence of genital ulcers , pregnancy , bloody cervical or vaginal discharge , abnormal vaginal discharge , cervical ectopy , Neisseria gonorrhoeae , Chlamydia trachomatis , Trichomonas vaginalis , an intermediate bacterial vaginosis score and HSV DNA detection . Similar factors were associated with genital HIV-1 RNA load . Conclusions RTIs were associated with increased presence and quantity of genital HIV-1 RNA in this population . These results highlight the importance of integrating effective RTI treatment into HIV care services To determine the frequency and risk factors for female to male sexual transmission of human immunodeficiency virus type 1 ( HIV-1 ) , a prospect i ve study was carried out in 422 men who had acquired a sexually transmitted disease ( STD ) from a group of prostitutes with a prevalence of HIV-1 infection of 85 % . The initial seroprevalence of HIV among the men was 12 % . 24 of 293 ( 8.2 % ) initially seronegative men seroconverted to HIV-1 . Newly acquired infection was independently associated with frequent prostitute contact ( risk ratio 3.2 , 95 % confidence interval 1.2 - 8.1 ) , with the acquisition of genital ulcer disease ( risk ratio 4.7 , 95 % confidence interval 1.3 - 17.0 ) , and with being uncircumcised ( risk ratio 8.2 , 95 % confidence interval 3.0 - 23.0 ) . 96 % of documented seroconversions occurred in men with one or both of the latter two risk factors . In a subgroup of 73 seronegative men who reported a single prostitute sexual contact , the frequency of HIV-1 infection was 8.2 % during 12 weeks of observation . No man without a genital ulcer seroconverted . A cumulative 43 % of uncircumcised men who acquired an ulcer seroconverted to HIV-1 after a single sexual exposure . These data indicate an extremely high rate of female to male transmission of HIV-1 in the presence of STD and confirm a causal relation between lack of male circumcision , genital ulcer disease , and susceptibility to HIV-1 infection BACKGROUND Syphilis remains an important source of morbidity worldwide . Long-acting penicillin is the only therapy currently recommended for syphilis in much of the world . Because of hesitation to use penicillin for fear of anaphylaxis , there is a need for an effective , well-tolerated alternative to penicillin for syphilis therapy . METHODS This multicenter , r and omized clinical trial was conducted in clinics for the treatment of persons with sexually transmitted diseases . We compared serological cure rates for human immunodeficiency virus (HIV)-negative persons with early syphilis treated with azithromycin at a dosage of 2.0 g administered orally as a single dose with cure rates for those treated with benzathine penicillin G at a dosage of 2.4 million units administered intramuscularly . RESULTS A total of 517 participants were enrolled in the trial . In the intention-to-treat analysis , after 6 months of follow-up , serological cure was observed in 180 ( 77.6 % ) of 232 azithromycin recipients and 186 ( 78.5 % ) of 237 penicillin recipients ( 1-sided lower bound 95 % confidence interval , 7.2 % ) . Nonserious adverse events were more common among azithromycin recipients than they were among penicillin recipients ( 61.5 % vs 46.3 % ) , and such adverse events were accounted for , in large part , by self-limited gastrointestinal complaints . CONCLUSIONS In this trial , the efficacy of azithromycin at a dosage of 2.0 g administered orally was equivalent to that of benzathine penicillin G for the treatment of early syphilis in persons without HIV infection Genital ulcers are implicated as a risk factor enhancing susceptibility to human immunodeficiency virus type 1 ( HIV-1 ) infection . A prospect i ve study to determine the incidence of and risk factors associated with acquisition of HIV-1 in women with genital ulcers was done . HIV-1-seronegative women with genital ulcers attending a clinic for sexually transmitted diseases in Nairobi were followed to HIV-1 seroconversion over a 6-month period . Of 81 women , 10 seroconverted to HIV-1 . The crude 6-month incidence of HIV-1 infection was 12 % . Risk factors associated with seroconversion included cervical ectopy ( rate ratio [ RR ] , 4.9 ; 95 % confidence interval [ CI ] , 1.5 - 15.6 ) and pelvic inflammatory disease ( RR , 6.3 ; 95 % CI , 1.9 - 20.4 ) . Thus , cervical ectopy and pelvic inflammatory disease may increase susceptibility to HIV-1 in women with genital ulcers Background : An association has been demonstrated between herpes simplex type 2 ( HSV-2 ) and HIV infection among men , but prospect i ve studies in women have yielded mixed results . Objective : To estimate the effects of prevalent and incident HSV-2 infection on subsequent HIV acquisition among women in two African countries . Design : Prospect i ve cohort study . Methods : HSV-2 and HIV serostatus were evaluated at enrollment and quarterly for 15–24 months among 4531 sexually active , HIV-uninfected women aged 18–35 years from Ug and a and Zimbabwe . The association between prior HSV-2 infection and HIV acquisition was estimated using a marginal structural discrete survival model , adjusted for covariates . Results : HSV-2 seroprevalence at enrollment was 52 % in Ug and a and 53 % in Zimbabwe ; seroincidence during follow-up was 9.6 and 8.8/100 person-years in Ug and a and Zimbabwe , respectively . In Ug and a , the hazard ratio ( HR ) for HIV was 2.8 [ 95 % confidence interval ( CI ) , 1.5–5.3 ] among women with seroprevalent HSV-2 and 4.6 ( 95 % CI , 1.6–13.1 ) among women with seroincident HSV-2 , adjusted for confounding . In Zimbabwe , the HR for HIV was 4.4 ( 95 % CI , 2.7–7.2 ) among women with seroprevalent HSV-2 , and 8.6 ( 95 % CI , 4.3–17.1 ) among women with seroincident HSV-2 , adjusted for confounding . The population attributable risk percent for HIV due to prevalent and incident HSV-2 infection was 42 % in Ug and a and 65 % in Zimbabwe . Conclusions : HSV-2 plays an important role in the acquisition of HIV among women . Efforts to implement known HSV-2 control measures , as well as identify additional measures to control HSV-2 , are urgently needed to curb the spread of HIV BACKGROUND Reports of neurosyphilis and invasion of cerebrospinal fluid by Treponema pallidum in patients with human immunodeficiency virus ( HIV ) infection have led to doubts about the adequacy of the recommended penicillin G benzathine therapy for early syphilis . METHODS In a multicenter , r and omized , double-blind trial , we assessed two treatments for early syphilis : 2.4 million units of penicillin G benzathine and that therapy enhanced with a 10-day course of amoxicillin and probenecid . The serologic and clinical responses of patients with and without HIV infection were studied during one year of follow-up . RESULTS From 1991 through 1994 , 541 patients were enrolled , including 101 patients ( 19 percent ) who had HIV infection but differed little from the uninfected patients in their clinical presentations . The rates at which chancres and rashes resolved did not differ significantly according to treatment assignment or HIV status . Serologically defined treatment failures were more common among the HIV-infected patients . The single clinical ly defined treatment failure was in an HIV-infected patient . Rates of serologically defined treatment failure did not differ according to treatment group ( 18 percent at six months with usual therapy ; 17 percent with enhanced therapy ) . T. pallidum was found at enrollment in the cerebrospinal fluid of 32 of 131 patients ( 24 percent ) and after therapy in 7 of 35 patients tested . None had clinical ly evident neurosyphilis , and the rate of detection of T. pallidum did not differ according to HIV status . CONCLUSIONS After treatment for primary or secondary syphilis , the HIV-infected patients responded less well serologically than the patients without HIV infection , but clinical ly defined failure was uncommon in both groups . Enhanced treatment with amoxicillin and probenecid did not improve the outcomes . Although T. pallidum was detected in cerebrospinal fluid before therapy in a quarter of the patients tested , such a finding did not predict treatment failure . The current recommendations for treating early syphilis appear adequate for most patients , whether or not they have HIV infection Background : Several studies suggest that herpes simplex virus type 2 ( HSV-2 ) may enhance HIV-1 transmission and disease progression . Methods : We conducted a r and omized , double-blind , placebo-controlled trial of aciclovir 400 mg twice daily for 3 months in 300 HSV-2/HIV-1 co-infected women not yet on highly active antiretroviral therapy ( HAART ) . Participants were evaluated prer and omization and at monthly visits for 3 months . Primary outcomes were the detection and quantity of genital HIV-1 RNA at the month 3 ( M3 ) visit . Analyses were also undertaken using data from all visits . The treatment effects on plasma HIV-1 RNA , CD4 + cell count and genital HSV-2 DNA were also assessed . Results : At M3 fewer women had detectable genital HIV in the aciclovir group compared to placebo , but this was not significant [ 61/132 ( 46 % ) vs. 71/137 ( 52 % ) , risk ratio ( RR ) 0.89 , 95 % confidence interval ( CI ) 0.70–1.14 ; P = 0.36 ] . There was also little difference in quantity of HIV-1 RNA among shedders ( + 0.13 log10 copies/ml , 95 % CI −0.14 to 0.39 ) at M3 . However , aciclovir significantly decreased the frequency of HIV-1 shedding over all visits [ adjusted odds ratio ( OR ) 0.57 , 95 % CI 0.36–0.89 ] . Significant reductions in M3 plasma HIV-1 RNA ( −0.34 log10 copies/ml , 95 % CI 0.15–0.54 ) , genital HSV-2 DNA ( 8 vs. 20 % , RR 0.37 , 95 % CI 0.19–0.73 ) and genital ulceration ( 8 vs. 18 % , RR 0.43 , 95 % CI 0.22–0.84 ) were observed in the aciclovir group . Conclusion : HSV-2 suppressive therapy , by reducing HIV-1 plasma viral load and altering the pattern of genital HIV-1 shedding , may contribute to the reduction in sexual transmission of HIV-1 and may delay the requirement for HAART initiation A r and omized , double-blind , placebo-controlled clinical trial was conducted in Nairobi , Kenya , to compare single-dose ciprofloxacin with a 7-day course of erythromycin for the treatment of chancroid . In all , 208 men and 37 women presenting with genital ulcers clinical ly compatible with chancroid were enrolled . Ulcer etiology was determined using culture techniques for chancroid , serology for syphilis , and a multiplex polymerase chain reaction for chancroid , syphilis , and herpes simplex virus ( HSV ) . Ulcer etiology was 31 % unmixed chancroid , 23 % unmixed syphilis , 16 % unmixed HSV , 15 % mixed etiology , and 15 % unknown . For 111 participants with chancroid , cure rates were 92 % with ciprofloxacin and 91 % with erythromycin . For all study participants , the treatment failure rate was 15 % , mostly related to ulcer etiologies of HSV infection or syphilis , and treatment failure was 3 times more frequent in human immunodeficiency virus-infected subjects than in others , mostly owing to HSV infection . Ciprofloxacin is an effective single-dose treatment for chancroid , but current recommendations for empiric therapy of genital ulcers may result in high treatment failure due to HSV infection BACKGROUND The probability of HIV-1 transmission per coital act in representative African population s is unknown . We aim ed to calculate this probability overall , and to estimate how it is affected by various factors thought to influence infectivity . METHODS 174 monogamous couples , in which one partner was HIV-1 positive , were retrospectively identified from a population cohort in Rakai , Ug and a. Frequency of intercourse and reliability of reporting within couples was assessed prospect ively . HIV-1 seroconversion was determined in the uninfected partners , and HIV-1 viral load was measured in the infected partners . Adjusted rate ratios of transmission per coital act were estimated by Poisson regression . Probabilities of transmission per act were estimated by log-log binomial regression for quartiles of age and HIV-1 viral load , and for symptoms or diagnoses of sexually transmitted diseases ( STDs ) in the HIV-1-infected partners . RESULTS The mean frequency of intercourse was 8.9 per month , which declined with age and HIV-1 viral load . Members of couples reported similar frequencies of intercourse . The overall unadjusted probability of HIV-1 transmission per coital act was 0.0011 ( 95 % CI 0.0008 - 0.0015 ) . Transmission probabilities increased from 0.0001 per act at viral loads of less than 1700 copies/mL to 0.0023 per act at 38 500 copies/mL or more ( p=0.002 ) , and were 0.0041 with genital ulceration versus 0.0011 without ( p=0.02 ) . Transmission probabilities per act did not differ significantly by HIV-1 subtypes A and D , sex , STDs , or symptoms of discharge or dysuria in the HIV-1-positive partner . INTERPRETATION Higher viral load and genital ulceration are the main determinants of HIV-1 transmission per coital act in this Ug and an population BACKGROUND Few data on the effect of human papillomavirus ( HPV ) infection on human immunodeficiency virus ( HIV ) acquisition are available . METHODS HIV-seronegative , sexually active , 18 - 24-year-old Kenyan men participating in a r and omized trial of male circumcision provided exfoliated penile cells from 2 anatomical sites ( glans/coronal sulcus and shaft ) at baseline . The GP5+/6 + polymerase chain reaction assay ascertained a wide range of HPV DNA types at the baseline visit . The risk of HIV infection was estimated using Kaplan-Meier methods and hazard ratios from proportional hazards models . RESULTS Of 2168 uncircumcised men with baseline HPV data , 1089 ( 50 % ) were positive for HPV DNA . The cumulative incidence of HIV infection by 42 months was 5.8 % ( 95 % confidence interval [ CI ] , 3.6%-7.9 % ) among men with HPV-positive glans/coronal sulcus specimens , versus 3.7 % [ 95 % CI , 1.8%-5.6 % ] among men with HPV-negative glans/coronal sulcus specimens ( P = .01 ) . Controlling for subsequent circumcision status , baseline herpes simplex virus type 2 serostatus , and sexual and sociodemographic risk factors , the hazard ratio for HIV infection among men with HPV-positive glans/coronal sulcus specimens was 1.8 ( 95 % CI , 1.1 - 2.9 ) , compared with men with HPV-negative glans/coronal sulcus specimens . CONCLUSION The results suggest an independent increased risk of HIV seroconversion among HPV-positive men . If this finding is confirmed in other studies , HPV prevention could be another tool for HIV prevention Background HIV-1 control in sub-Saharan Africa requires cost-effective and sustainable programmes that promote behaviour change and reduce cofactor sexually transmitted infections ( STIs ) at the population and individual levels . Methods and Findings We measured the feasibility of community-based peer education , free condom distribution , income-generating projects , and clinic-based STI treatment and counselling services and evaluated their impact on the incidence of HIV-1 measured over a 3-y period in a cluster-r and omised controlled trial in eastern Zimbabwe . Analysis of primary outcomes was on an intention-to-treat basis . The income-generating projects proved impossible to implement in the prevailing economic climate . Despite greater programme activity and knowledge in the intervention communities , the incidence rate ratio of HIV-1 was 1.27 ( 95 % confidence interval [ CI ] 0.92–1.75 ) compared to the control communities . No evidence was found for reduced incidence of self-reported STI symptoms or high-risk sexual behaviour in the intervention communities . Males who attended programme meetings had lower HIV-1 incidence ( incidence rate ratio 0.48 , 95 % CI 0.24–0.98 ) , and fewer men who attended programme meetings reported unprotected sex with casual partners ( odds ratio 0.45 , 95 % CI 0.28–0.75 ) . More male STI patients in the intervention communities reported cessation of symptoms ( odds ratio 2.49 , 95 % CI 1.21–5.12 ) . Conclusions Integrated peer education , condom distribution , and syndromic STI management did not reduce population -level HIV-1 incidence in a declining epidemic , despite reducing HIV-1 incidence in the immediate male target group . Our results highlight the need to assess the community-level impact of interventions that are effective amongst targeted population sub-groups BACKGROUND The study tested the hypothesis that community-level control of sexually transmitted disease ( STD ) would result in lower incidence of HIV-1 infection in comparison with control communities . METHODS This r and omised , controlled , single-masked , community-based trial of intensive STD control , via home-based mass antibiotic treatment , took place in Rakai District , Ug and a. Ten community clusters were r and omly assigned to intervention or control groups . All consenting residents aged 15 - 59 years were enrolled ; visited in the home every 10 months ; interviewed ; asked to provide biological sample s for assessment of HIV-1 infection and STDs ; and were provided with mass treatment ( azithromycin , ciprofloxacin , metronidazole in the intervention group , vitamins/anthelmintic drug in the control ) . Intention-to-treat analyses used multivariate , paired , cluster-adjusted rate ratios . FINDINGS The baseline prevalence of HIV-1 infection was 15.9 % . 6602 HIV-1-negative individuals were enrolled in the intervention group and 6124 in the control group . 75.0 % of intervention-group and 72.6 % of control-group participants provided at least one follow-up sample for HIV-1 testing . At enrolment , the two treatment groups were similar in STD prevalence rates . At 20-month follow-up , the prevalences of syphilis ( 352/6238 [ 5.6 % ] ) vs 359/5284 [ 6.8 % ] ; rate ratio 0.80 [ 95 % CI 0.71 - 0.89 ] ) and trichomoniasis ( 182/1968 [ 9.3 % ] vs 261/1815 [ 14.4 % ] ; rate ratio 0.59 [ 0.38 - 0.91 ] ) were significantly lower in the intervention group than in the control group . The incidence of HIV-1 infection was 1.5 per 100 person-years in both groups ( rate ratio 0.97 [ 0.81 - 1.16 ] ) . In pregnant women , the follow-up prevalences of trichomoniasis , bacterial vaginosis , gonorrhoea , and chlamydia infection were significantly lower in the intervention group than in the control group . No effect of the intervention on incidence of HIV-1 infection was observed in pregnant women or in stratified analyses . INTERPRETATION We observed no effect of the STD intervention on the incidence of HIV-1 infection . In the Rakai population , a substantial proportion of HIV-1 acquisition appears to occur independently of treatable STD cofactors BACKGROUND Pilot studies suggest that a single , 2-g oral dose of azithromycin may be an alternative to a 2.4-MU intramuscular dose of penicillin G benzathine in the prevention and treatment of syphilis . We evaluated the efficacy of treatment with azithromycin in a developing country . METHODS A total of 328 subjects , 25 with primary and 303 with high-titer ( a titer of at least 1:8 on a rapid plasmin reagin [ RPR ] test ) latent syphilis , were recruited through screening of high-risk population s in Mbeya , Tanzania , and r and omly assigned to receive 2 g of azithromycin orally ( 163 subjects ) or 2.4 million units of penicillin G benzathine intramuscularly ( 165 subjects ) . The primary outcome was treatment efficacy , with cure defined serologically ( a decline in the RPR titer of at least two dilutions by nine months after treatment ) and , in primary syphilis , by epithelialization of ulcers within one or two weeks . RESULTS The average age of participants was 27.0 years , 235 ( 71.6 percent ) were female , and 171 ( 52.1 percent ) were seropositive for human immunodeficiency virus . Cure rates were 97.7 percent ( 95 percent confidence interval , 94.0 to 99.4 ) in the azithromycin group and 95.0 percent ( 95 percent confidence interval , 90.6 to 97.8 ) in the penicillin G benzathine group ( 95 percent confidence interval for the difference , -1.7 to 7.1 percent ) , achieving prespecified criteria for equivalence . Cure rates were also similar three and six months after treatment in the two groups and in all subgroups . Cure rates at three months were 59.4 percent ( 95 percent confidence interval , 51.8 to 67.1 ) in the azithromycin group and 59.5 percent ( 95 percent confidence interval , 51.8 to 67.3 ) in the penicillin G benzathine group and at six months were 85.5 percent ( 95 percent confidence interval , 79.4 to 90.6 ) and 81.5 percent ( 95 percent confidence interval , 74.8 to 87.4 ) , respectively . CONCLUSIONS Single-dose oral azithromycin is effective in treating syphilis and may be particularly useful in developing countries in which the use of penicillin G benzathine injections is problematic . However , recent reports of azithromycin-resistant Treponema pallidum in the United States indicate the importance of continued monitoring for resistance Chancroid is gaining importance as a sexually transmitted disease because of its association with transmission of human immunodeficiency virus type 1 ( HIV-1 ) . Effective , simply administered therapy for chancroid is necessary . Fleroxacin is effective against Haemophilus ducreyi in vitro . We performed an initial r and omized clinical trial to assess the efficacy of fleroxacin for treatment of chancroid in Nairobi , Kenya . Fifty-three men with culture-positive chancroid were r and omly assigned to receive either 200 mg ( group 1 ) or 400 mg ( group 2 ) of fleroxacin as a single oral dose . Groups 1 and 2 were similar with regard to severity of disease , bubo formation , and HIV-1 status . A satisfactory clinical response to therapy was noted in 23 of 26 patients ( 88 % ) in group 1 and 18 of 23 patients ( 78 % ) in group 2 . Bacteriological failure occurred in 1 of 26 evaluable patients ( 4 % ) in group 1 and 4 of 23 evaluable patients ( 17 % ) in group 2 . Two of 37 HIV-1-seronegative men ( 5 % ) and 3 of 11 HIV-1-infected men ( 27 % ) were bacteriological failures . Fleroxacin , 200 or 400 mg as a single oral dose , is efficacious therapy for microbiologically proven chancroid in patients who do not have concurrent HIV-1 infection . Among HIV-1-infected men , a single dose of 200 or 400 mg of fleroxacin is inadequate therapy for chancroid OBJECTIVES The heterosexual spread of HIV-1 is occurring at different rates in different parts of the world . The transmission probability of HIV-1 per sexual contact is low , but may be greatly enhanced by several cofactors . Sexually transmitted diseases ( STD ) , especially genital ulcers , may be such factors . So far , epidemiological evidence that other STD facilitate HIV-1 transmission is weak . The objective of this study was to determine whether treatable STD enhanced sexual transmission of HIV-1 in a cohort of female prostitutes in Kinshasa , Zaire . METHODS We conducted a nested case-control study of 431 initially HIV-1-negative women followed prospect ively for a mean duration of 2 years ( with monthly STD check-ups and 3-monthly HIV-1 serology ) . Cases ( seroconverters , n = 68 ) were compared with controls ( women who remained HIV-1-negative , n = 126 ) for incidence of STD and sexual exposure during the presumed period of HIV-1 acquisition . RESULTS The annual incidence of HIV-1 in this cohort was 9.8 % . Seroconverters were younger than HIV-1-negative women ( mean age , 24.6 versus 26.8 years ; P = 0.04 ) . During the period of HIV-1 acquisition , cases had a much higher incidence of gonorrhoea , chlamydial infection and trichomoniasis , and engaged in unprotected sex with clients and partners more frequently than controls . After controlling for sexual exposure by multivariate analysis , adjusted odds ratios for seroconversion were 4.8 [ 95 % confidence interval ( CI ) , 2.4 - 9.8 ] for gonorrhoea , 3.6 ( 95 % CI , 1.4 - 9.1 ) for chlamydial infection and 1.9 ( 95 % CI , 0.9 - 4.1 ) for trichomoniasis . Genital ulcers were more frequent in cases than controls , but much less common than other STD . CONCLUSION Non-ulcerative STD were risk factors for sexual transmission of HIV-1 in women , after controlling for sexual exposure . Because of their high prevalence in some population s , non-ulcerative STD may represent a considerable population -attributable risk in the transmission of HIV-1 worldwide . The identification of treatable STD as risk factors for HIV-1 transmission offers an important additional strategy for the prevention of HIV/AIDS Objective : To describe the design and first-round survey results of a trial of intensive sexually transmitted disease ( STD ) control to reduce HIV-1 incidence . Study design : R and omized , controlled , community-based trial in Rakai District , Ug and a. Methods : In this ongoing study , 56 communities were grouped into 10 clusters design ed to encompass social/sexual networks ; clusters within blocks were r and omly assigned to the intervention or control arm . Every 10 months , all consenting resident adults aged 15–59 years are visited in the home for interview and sample collection ( serological sample , urine , and , in the case of women , self-administered vaginal swabs ) . Sera are tested for HIV-1 , syphilis , gonorrhea , chlamydia , trichomonas and bacterial vaginosis . Following interview , all consenting adults are offered directly observed , single oral dose treatment ( STD treatment in the intervention arm , anthelminthic and iron-folate in the control arm ) . Treatment is administered irrespective of symptoms or laboratory testing ( mass treatment strategy ) . Both arms receive identical health education , condom and serological counseling services . Results : In the first home visit round , the study enrolled 5834 intervention and 5784 control arm subjects . Compliance with interview , sample collection and treatment was high in both arms ( over 90 % ) . Study arm population s were comparable with respect to sociodemographic and behavioral characteristics , and baseline HIV and STD rates . The latter were high : 16.9 % of all subjects were HIV-positive , 10.0 % had syphilis , and 23.8 % of women had trichomonas and 50.9 % had bacterial vaginosis . Conclusions : Testing the effects of STD control on AIDS prevention is feasible in this Ug and an setting Background and Objectives Chancroid is endemic in sub-Saharan Africa and enhances the sexual transmission of the human immunodeficiency virus Type 1 ( HIV-1 ) . Azithromycin is an orally absorbed macrolide antibiotic that is active against Haemophilus ducreyi , the causative agent of chancroid , and has pharmacokinetic properties that are suitable for single dosing . Study Design In a r and omized single-blinded study of 127 men presenting to a referral STD clinic with culture proven chancroid , we compared the efficacy of azithromycin , administered as a single 1 g dose , with erythromycin 500 mg given 4 times daily for 7 days . Results : Cure rates were 89 % ( 73 of 82 ) in the azithromycin group and 91 % ( 41 of 45 ) in the erythromycin group . A failure to respond to treatment was associated with HIV-1 seropositivity and a lack of circumcision . Both regimens were well tolerated . Conclusions Azithromycin , given as a single 1 g oral dose , is an effective treatment for chancroid in men , and offers major prescribing advantages over erythromycin BACKGROUND Infection with herpes simplex virus type 2 ( HSV-2 ) is associated with an increased risk of acquiring infection with the human immunodeficiency virus ( HIV ) . This study tested the hypothesis that HSV-2 suppressive therapy reduces the risk of HIV acquisition . METHODS Female workers at recreational facilities in northwestern Tanzania who were 16 to 35 years of age were interviewed and underwent serologic testing for HIV and HSV-2 . We enrolled female workers who were HIV-seronegative and HSV-2-seropositive in a r and omized , double-blind , placebo-controlled trial of suppressive treatment with acyclovir ( 400 mg twice daily ) . Participants attended mobile clinics every 3 months for a follow-up period of 12 to 30 months , depending on enrollment date . The primary outcome was the incidence of infection with HIV . We used a modified intention-to-treat analysis ; data for participants who became pregnant were censored . Adherence to treatment was estimated by a tablet count at each visit . RESULTS A total of 821 participants were r and omly assigned to receive acyclovir ( 400 participants ) or placebo ( 421 participants ) ; 679 ( 83 % ) completed follow-up . Mean follow-up for the acyclovir and placebo groups was 1.52 and 1.62 years , respectively . The incidence of HIV infection was 4.27 per 100 person-years ( 27 participants in the acyclovir group and 28 in the placebo group ) , and there was no overall effect of acyclovir on the incidence of HIV ( rate ratio for the acyclovir group , 1.08 ; 95 % confidence interval , 0.64 to 1.83 ) . The estimated median adherence was 90 % . Genital HSV was detected in a similar proportion of participants in the two study groups at 6 , 12 , and 24 months . No serious adverse events were attributable to treatment with acyclovir . CONCLUSIONS These data show no evidence that acyclovir ( 400 mg twice daily ) as HSV suppressive therapy decreases the incidence of infection with HIV . ( Current Controlled Trials number , IS RCT N35385041 [ controlled-trials.com ] . ) Objective By a r and omised , double-blind , placebo-controlled trial of aciclovir 800 mg twice daily for 5 days added to the syndromic management of genital ulcer disease ( GUD ) to determine the impact on ulcer healing and HIV outcomes . Methods Patients presenting with GUD in Malawi were evaluated for HIV and herpes simplex virus type-2 ( HSV-2 ) serologies , ulcer aetiology , lesional , genital and plasma HIV-1 RNA and CD4 + count . Patients were followed up at days 2 , 4 , 7 , 14 and 28 . The primary study outcome was ulcer healing at day 14 , with secondary outcomes being lesional and genital HIV-1 shedding at day 14 and HIV-1 plasma viral load at day 28 among HIV-1/HSV-2 co-infected individuals . Results Four hundred and twenty-two patients ( 74 % male ) were r and omised ( 208 to aciclovir , 214 to placebo ) , of whom 61 % were HIV-1 seropositive and 72 % HSV-2 seropositive ; 67 % ( 267/398 ) had HSV-2 ulcers . 85 % of ulcers were healed at day 14 with no difference between treatment arms ( risk ratio (RR)=1.02 , 95 % CI 0.93 to 1.11 ) . Among 244 HIV-1/HSV-2 co-infected individuals , aciclovir reduced lesional HIV-1 RNA ( adjusted RR=0.64 , 95 % CI 0.41 to 0.99 ) and seminal HIV-1 RNA ( adjusted RR=0.59 , 95 % CI 0.40 to 0.88 ) , but not cervical HIV-1 RNA or plasma HIV-1 RNA . Conclusions Episodic HSV treatment with aciclovir added to syndromic management did not produce a significant clinical benefit in this African population Chancroid is linked to the spread of human immunodeficiency virus type 1 ( HIV-1 ) in East Africa . Effective , easily administered therapy is a priority for the control of Haemophilus ducreyi . The efficacy of a single oral dose of fleroxacin , 400 mg , was compared to a 3-day oral course of trimethoprim-sulfamethoxazole ( TMP-SMZ ) , 160/800 mg , twice daily for the treatment of chancroid in 98 HIV-1-seronegative men in Nairobi , Kenya . No differences were noted between the two groups with respect to demographic characteristics , sexual behavior , and clinical characteristics . Culture-proven failure occurred in 1 ( 3 % ) of 36 fleroxacin-treated patients and in 11 ( 30 % ) of 37 TMP-SMZ-treated patients ( P = .005 ) . Fleroxacin , as a single oral dose , is an effective treatment for culture-proven chancroid in patients who are HIV-1 seronegative . TMP-SMZ is no longer predictably effective due to the recent emergence of resistance to both sulfonamides and to trimethoprim This article introduces the approach of GRADE to rating quality of evidence . GRADE specifies four categories-high , moderate , low , and very low-that are applied to a body of evidence , not to individual studies . In the context of a systematic review , quality reflects our confidence that the estimates of the effect are correct . In the context of recommendations , quality reflects our confidence that the effect estimates are adequate to support a particular recommendation . R and omized trials begin as high- quality evidence , observational studies as low quality . " Quality " as used in GRADE means more than risk of bias and so may also be compromised by imprecision , inconsistency , indirectness of study results , and publication bias . In addition , several factors can increase our confidence in an estimate of effect . GRADE provides a systematic approach for considering and reporting each of these factors . GRADE separates the process of assessing quality of evidence from the process of making recommendations . Judgments about the strength of a recommendation depend on more than just the quality of evidence Background Penicillin is the only medication currently recommended for treatment of early syphilis in non-penicillin-allergic patients . Preliminary data suggest that azithromycin may be effective for syphilis therapy . Study Design This was a r and omized , comparative pilot study of intramuscular injections of benzathine penicillin G and two oral azithromycin regimens for treatment of syphilis . Methods We r and omly assigned patients with early syphilis to treatment with either intramuscular injections of 2.4 million units of benzathine penicillin G or azithromycin administered orally , either as a single 2.0-g dose or as two 2.0-g doses given 1 week apart . Serological response to therapy was evaluated at 3 , 6 , 9 , and 12 months following therapy . Participants whose rapid plasma reagin ( RPR ) test became nonreactive or whose RPR titer decreased ≥2 dilutions were classified as responding to therapy . When serological tests did not show a response to therapy , the treatment was classified as a failure if RPR titers increased ≥2 dilutions . Nonresponders were those whose serologic titers remained within ±1 dilution of the initial RPR titer . Results Cumulative response rates were as follows : benzathine penicillin G , 86 % ( 12 of 14 ) ; azithromycin , 2.0-g single dose , 94 % ( 16 of 17 ) ; and azithromycin , two 2.0-g doses given 1 week apart , 83 % ( 24 of 29 ) . Therapy failed for one patient treated with benzathine penicillin and one patient treated with the two-dose azithromycin regimen , whereas in six patients the clinical manifestations of infection resolved but there was no serological response . Conclusion Oral therapy with 2.0 g of azithromycin as a single dose or as two doses 1 week apart is a promising alternative to therapy with benzathine penicillin G for syphilis and should be studied further Background : Herpes simplex virus type 2 infection is important in the HIV epidemic and may contribute to increased HIV transmission . We evaluated the effect of suppressive acyclovir therapy on cervicovaginal HIV-1 shedding . Methods : HIV-1- and herpes simplex virus type 2-coinfected women aged 18 - 49 years with CD4 counts > 200 cells/μL were enrolled in a r and omized crossover trial of suppressive acyclovir therapy ( NCT00362596 , http://www . clinical trials.gov ) . For each woman , monthly plasma and weekly cervicovaginal lavage specimens were collected ; the mean of the monthly median cervicovaginal lavage HIV-1 viral load and plasma HIV-1 viral load was compared . Results : Sixty-seven women were enrolled ; at baseline , median CD4 count was 366 cells/μL , and median HIV-1 plasma viral load was 4.6 log10 copies/mL. The mean cervicovaginal lavage HIV-1 viral load was 1.9 ( SD 0.8 ) log10 copies/mL during the acyclovir month and 2.2 ( SD 0.7 ) log10 copies/mL during the placebo month ( P < 0.0001 ) ; the mean decrease in HIV was 0.3 log10 copies/mL. The mean plasma HIV viral load during the acyclovir month ( 3.78 log10 copies/mL ) was reduced compared with the placebo month ( 4.26 log10 copies/mL , P < 0.001 ) . Conclusions : Acyclovir reduced HIV genital shedding and plasma viral load among HIV-1- and herpes simplex virus type 2-coinfected women . Further data from clinical trials will examine the effect of suppressive therapy on HIV transmission BACKGROUND Little is known about the impact of episodic treatment of herpes on human immunodeficiency virus type 1 ( HIV-1 ) . METHODS Women from Ghana and the Central African Republic who had genital ulcers were enrolled in a r and omized , double-blind , placebo-controlled trial of acyclovir plus antibacterials and were monitored for 28 days . Ulcer etiologies and detection of lesional HIV-1 RNA were determined by polymerase chain reaction ( PCR ) . Cervicovaginal HIV-1 RNA and herpes simplex virus type 2 ( HSV-2 ) DNA and plasma HIV-1 RNA were quantitated by real-time PCR . Primary analyses included 118 HIV-1-infected women with HSV-2 ulcers ( 54 of whom were given acyclovir and 64 of whom were given placebo ) . RESULTS Acyclovir had little impact on ( 1 ) detection of cervicovaginal HIV-1 RNA ( risk ratio [ RR ] , 0.96 ; 95 % confidence interval [ CI ] , 0.8 - 1.2 ) at day 7 of treatment , ( 2 ) the mean cervicovaginal HIV-1 RNA load ( -0.06 log(10 ) copies/mL ; 95 % CI , -0.4 to 0.3 log(10 ) copies/mL ) at day 7 of treatment , or ( 3 ) the plasma HIV-1 RNA load ( + 0.09 log(10 ) copies/mL ; 95 % CI , -0.1 to 0.3 log(10 ) copies/mL ) at day 14 of treatment . At day 7 , women receiving acyclovir were less likely to have detectable lesional HIV-1 RNA ( RR , 0.70 ; 95 % CI , 0.4 - 1.2 ) or cervicovaginal HSV-2 DNA ( RR , 0.69 ; 95 % CI , 0.4 - 1.3 ) , had a lower quantity of HSV-2 DNA ( -0.99 log(10 ) copies/mL ; 95 % CI , -1.8 to -0.2 log(10 ) copies/mL ) , and were more likely to have a healed ulcer ( RR , 1.26 ; 95 % CI , 0.9 - 1.9 ) . CONCLUSION Episodic therapy for herpes reduced the quantity of cervicovaginal HSV-2 DNA and slightly improved ulcer healing , but it did not decrease genital and plasma HIV-1 RNA loads . TRIAL REGISTRATION Clinical Trials.gov identifier NCT00158483 BACKGROUND Treatment of sexually-transmitted infections ( STIs ) and behavioural interventions are the main methods to prevent HIV in developing countries . We aim ed to assess the effect of these interventions on incidence of HIV-1 and other sexually-transmitted infections . METHODS We r and omly allocated all adults living in 18 communities in rural Ug and a to receive behavioural interventions alone ( group A ) , behavioural and STI interventions ( group B ) , or routine government health services and community development activities ( group C ) . The primary outcome was HIV-1 incidence . Secondary outcomes were incidence of herpes simplex virus type 2 ( HSV2 ) and active syphilis and prevalence of gonorrhoea , chlamydia , reported genital ulcers , reported genital discharge , and markers of behavioural change . Analysis was per protocol . FINDINGS Compared with group C , the incidence rate ratio of HIV-1 was 0.94 ( 0.60 - 1.45 , p=0.72 ) in group A and 1.00 ( 0.63 - 1.58 , p=0.98 ) in group B , and the prevalence ratio of use of condoms with last casual partner was 1.12 ( 95 % CI 0.99 - 1.25 ) in group A and 1.27 ( 1.02 - 1.56 ) in group B. Incidence of HSV2 was lower in group A than in group C ( incidence rate ratio 0.65 , 0.53 - 0.80 ) and incidence of active syphilis for high rapid plasma reagent test titre and prevalence of gonorrhoea were both lower in group B than in group C ( active syphilis incidence rate ratio , 0.52 , 0.27 - 0.98 ; gonorrhoea prevalence ratio , 0.25 , 0.10 - 0.64 ) . INTERPRETATION The interventions we used were insufficient to reduce HIV-1 incidence in rural Ug and a , where secular changes are occurring . More effective STI and behavioural interventions need to be developed for HIV control in mature epidemics To assess the effect of treatment of vaginal infections on vaginal shedding of cell-free human immunodeficiency virus type 1 ( HIV-1 ) and HIV-1-infected cells , HIV-1-seropositive women were examined before and after treatment of C and ida vulvovaginitis , Trichomonas vaginitis , and bacterial vaginosis . For C and ida ( n=98 ) , vaginal HIV-1 RNA decreased from 3.36 to 2.86 log(10 ) copies/swab ( P<.001 ) , as did the prevalence of HIV-1 DNA ( 36 % to 17 % ; odds ratio [ OR ] , 2.8 ; 95 % confidence interval [ CI ] , 1.3 - 6.5 ) . For Trichomonas vaginitis ( n=55 ) , HIV-1 RNA decreased from 3.67 to 3.05 log(10 ) copies/swab ( P<.001 ) , but the prevalence of HIV-1 DNA remained unchanged ( 22%-25 % ; OR , 0.8 ; 95 % CI , 0.3 - 2.2 ) . For bacterial vaginosis ( n=73 ) , neither the shedding of HIV-1 RNA ( from 3.11 to 2.90 log(10 ) copies/swab ; P=.14 ) nor the prevalence of DNA ( from 21 % to 23 % ; OR , 0.8 ; 95 % CI , 0.3 - 2.0 ) changed . Vaginal HIV-1 decreased 3.2- and 4.2-fold after treating C and ida and Trichomonas , respectively . These data suggest that HIV-1 transmission intervention strategies that incorporate diagnosis and treatment of these prevalent infections warrant evaluation Objective : To estimate the effects of reproductive tract infections ( RTIs ) on HIV acquisition among Zimbabwean and Ug and an women . Methods : A multicenter prospect i ve observational cohort study enrolled 4439 HIV-uninfected women aged 18 to 35 attending family planning clinics in Zimbabwe and Ug and a. Participants were interviewed , and tested for HIV and RTIs every 3 months for 15 to 24 months . They received HIV risk reduction counseling , male condoms , and treatment for curable RTIs . Results : Despite HIV risk reduction counseling and regular screening and treatment for RTIs , the HIV incidence did not decline during the study . Positive HSV-2 serostatus at baseline ( hazard ratio [ HR ] = 3.69 , 95 % confidence interval = 2.45–5.55 ) , incident HSV-2 ( HR = 5.35 , 3.06–9.36 ) , incident Neisseria gonorrhoeae ( HR = 5.46 , 3.41–8.75 ) , and altered vaginal flora during the study ( bacterial vaginosis [ BV ] : HR = 2.12 , 1.50–3.01 ; and intermediate flora : HR = 2.02 , 1.39–2.95 ) were independently associated with HIV acquisition after controlling for demographic and behavioral covariates and other RTIs ( Treponema pallidum , Chlamydia trachomatis , Trichomonas vaginalis , and vaginal yeasts ) . For N. gonorrhoeae , C. trachomatis , T. vaginalis , and vaginal yeasts , the risk of HIV acquisition increased when the infection was identified at the visit before the HIV-detection visit or with the duration of infection . Population attributable risk percent ( PAR% ) calculations show that HSV-2 contributes most to acquisition of new HIV infections ( 50.4 % for baseline HSV-2 and 7.9 % for incident HSV-2 ) , followed by altered vaginal flora ( 17.2 % for bacterial vaginosis and 11.8 % for intermediate flora ) . Conclusions : A substantial proportion of new HIV infections in Zimbabwean and Ug and an women are attributable to RTIs , particularly HSV-2 and altered vaginal flora We assess the relative contribution of viral and bacterial sexually transmitted infections ( STIs ) on HIV acquisition among southern African women in a nested case-control study within the Methods for Improving Reproductive Health in Africa ( MIRA ) trial . Cases were women with incident HIV infection ; controls were HIV-uninfected at the time of case seroconversion selected in a 1 to 3 case to control ratio ( risk-set sampling ) , matched on study site and time of follow-up . Conditional logistic regression models were used to calculate adjusted odds ratios ( AORs ) and population -attributable fractions ( PAF ) . Among 4948 enrolled women , we analysed 309 cases and 927 controls . The overall HIV incidence rate was 4.0 per 100 women-years . The incidence of HIV infection was markedly higher in women who had prevalent Herpes simplex virus type 2 ( HSV-2 ) ( AOR : 2.14 ; 95 % confidence interval [ CI ] : 1.55–2.96 ) , incident HSV-2 ( AOR : 4.43 ; 95 % CI : 1.77–11.05 ) and incident Neisseria gonorrhoeae ( AOR : 6.92 ; 95 % CI : 3.01–15.90 ) . The adjusted PAF of HIV incidence for prevalent HSV-2 was 29.0 % ( 95 % CI : 16.8–39.3 ) , for incident HSV-2 2.1 % ( 95 % CI : 0.6–3.6 ) and for incident N. gonorrhoeae 4.1 % ( 95 % CI : 2.5–5.8 ) . Women 's greatest risk factors for HIV acquisition were incident bacterial and viral STIs . Women-centred interventions aim ed at decreasing HIV incidence in young African women need to address these common co-morbid conditions Objective : To investigate correlates of herpes simplex virus type 2 ( HSV-2 ) DNA and HIV-1 RNA among women with genital ulcer disease ( GUD ) . Design : Baseline data from a r and omized placebo-controlled trial of episodic herpes treatment in Ghana and the Central African Republic . Methods : GUD aetiology was determined by polymerase chain reaction ( PCR ) from a lesional swab . Real-time PCR was used to quantify HIV-1 RNA , and HSV-2 DNA in cervicovaginal lavages ( CVL ) and HIV-1 RNA in plasma . Genital infection was defined as the presence of virus in the lesion or CVL . Results : Of 441 women enrolled , 79.0 % were HSV-2 seropositive , 46.6 % were HIV-1 seropositive , and 50.0 % had an HSV-2 ulcer . Among 180 HSV-2/HIV-1 co-infected women , cervicovaginal HIV-1 RNA was detected more frequently in women with HSV-2 ulcers ( 67.9 % ) or cervicovaginal HSV-2 DNA only ( 72.3 % ) compared with women without genital HSV-2 infection ( 42.4 % ) ( P = 0.004 ) . Women with genital HSV-2 infection had higher median cervicovaginal HIV-1-RNA loads ( 3.14 log10 copies/mL versus 2.10 log10 copies/mL ; P = 0.003 ) , higher plasma HIV-1-RNA loads ( median 5.10 versus 4.65 log10 copies/mL ; P = 0.07 ) , and lower median CD4 cell counts ) ( 198 versus 409 cells/mm3 , P = 0.03 ) . Cervicovaginal HIV-1 RNA and HSV-2 DNA were significantly correlated after adjusting for plasma HIV-1 RNA and CD4 cell counts ( P < 0.001 ) and a 10-fold increase in cervicovaginal HSV-2 DNA was associated with a 1.7-fold increase in plasma HIV-1 RNA ( P = 0.003 ) . Conclusion : Genital HSV-2 infection is associated with increased cervicovaginal and plasma HIV-1 RNA among co-infected women with genital ulcers , independently of the level of immunodeficiency , highlighting the close interaction between these two viruses and the role of HSV-2 as a co-factor for the sexual transmission of HIV-1 BACKGROUND Across many observational studies , herpes simplex virus type 2 ( HSV-2 ) infection is associated with two-fold to three-fold increased risk for HIV-1 infection . We investigated whether HSV-2 suppression with aciclovir would reduce the risk of HIV-1 acquisition . METHODS We undertook a double-blind , r and omised , placebo-controlled phase III trial in HIV-negative , HSV-2 seropositive women in Africa and men who have sex with men ( MSM ) from sites in Peru and the USA . Participants were r and omly assigned by block r and omisation to twice daily aciclovir 400 mg ( n=1637 ) or matching placebo ( n=1640 ) for 12 - 18 months , and were seen monthly for dispensation of study drug , adherence counselling and measurement by pill count and self-reporting , and risk reduction counselling , and every 3 months for genital examination and HIV testing . The primary outcome was HIV-1 acquisition and secondary was incidence of genital ulcers . Analysis was by intention to treat . This study is registered with Clinical Trials.gov , number NCT00076232 . FINDINGS 3172 participants ( 1358 women , 1814 MSM ) were included in the primary data set ( 1581 in aciclovir group , 1591 in control group ) . The incidence of HIV-1 was 3.9 per 100 person-years in the aciclovir group ( 75 events in 1935 person-years of follow-up ) and 3.3 per 100 person-years in the placebo group ( 64 events in 1969 person-years of follow-up ; hazard ratio 1.16 [ 95 % CI 0.83 - 1.62 ] ) . Incidence of genital ulcers on examination was reduced by 47 % ( relative risk 0.53 [ 0.46 - 0.62 ] ) and HSV-2 positive genital ulcers by 63 % ( 0.37 [ 0.31 - 0.45 ] ) in the aciclovir group . Adherence to dispensed study drug was 94 % in the aciclovir group and 94 % in the placebo group , and 85 % of expected doses in the aciclovir group and 86 % in the placebo group . Retention was 85 % at 18 months in both groups ( 1028 of 1212 in aciclovir group , 1030 of 1208 in placebo group ) . We recorded no serious events related to the study drug . INTERPRETATION Our results show that suppressive therapy with st and ard doses of aciclovir is not effective in reduction of HIV-1 acquisition in HSV-2 seropositive women and MSM . Novel strategies are needed to interrupt interactions between HSV-2 and HIV-1 Objectives : Suppressive herpes simplex virus ( HSV ) therapy can decrease plasma , cervical , and rectal HIV-1 levels in HIV-1/HSV-2 co-infected persons . We evaluated the effect of HSV-2 suppression on seminal HIV-1 levels . Design : Twenty antiretroviral therapy (ART)-naive HIV-1/HSV-2 men who have sex with men ( MSM ) in Lima , Peru , with CD4 > 200 cells/μl r and omly received valacyclovir 500 mg twice daily or placebo for 8 weeks , then the alternative regimen for 8 weeks after a 2-week washout . Peripheral blood and semen specimens were collected weekly . Anogenital swab specimens for HSV DNA were self-collected daily and during clinic visits . Methods : HIV-1 RNA was quantified in seminal and blood plasma by TaqMan real-time polymerase chain reaction ( RT-PCR ) or Roche Amplicor Monitor assays . HSV and seminal cytomegalovirus ( CMV ) were quantified by RT-PCR . Linear mixed models examined differences within participants by treatment arm . Results : Median CD4 cell count of participants was 424 cells/μl . HIV-1 was detected in 71 % of 231 semen specimens . HSV was detected from 29 and 4.4 % of swabs on placebo and valacyclovir , respectively ( P < 0.001 ) . Valacyclovir significantly reduced the proportion of days with detectable seminal HIV-1 ( 63 % during valacyclovir vs. 78 % during placebo ; P = 0.04 ) . Seminal HIV-1 quantity was 0.25 log10 copies/ml lower [ 95 % confidence interval ( CI ) −0.40 to −0.10 ; P = 0.001 ] during the valacyclovir arm compared with placebo , a 44 % reduction . CD4 cell count ( P = 0.32 ) and seminal cellular CMV quantity ( P = 0.68 ) did not predict seminal plasma HIV-1 level . Conclusions : Suppressive valacyclovir reduced seminal HIV-1 levels in HIV-1/HSV-2 co-infected MSM not receiving ART . The significance of this finding will be evaluated in a trial with HIV-1 transmission as the outcome BACKGROUND Our study evaluated correlates of human immunodeficiency virus (HIV)-1 lesional shedding among men with genital ulcer disease ( GUD ) . METHODS Participants were recruited at primary health care clinics as part of a r and omized trial of episodic acyclovir among men with GUD . This analysis was done among HIV-positive men identified at baseline . Participants were serologically screened for HIV infection , syphilis , and herpes simplex virus type 2 infection and for urethritis and ulcer etiology by polymerase chain reaction . Plasma and genital ulcer HIV-1 loads and CD4 cell counts were quantified . We evaluated variables associated with the presence and quantity of HIV-1 in ulcers . RESULTS Among 387 HIV-positive men , the median plasma HIV-1 load and CD4 cell count were 87,200 copies/mL and 282 cells/mm(3 ) . Overall , 173 ( 45.6 % ) had detectable HIV-1 RNA in ulcers . Men with Trichomonas vaginalis infection had higher ulcer viral loads on average than did those who were not infected ( mean difference , 0.62 ; 95 % confidence interval [ CI ] , 0.07 - 1.2 ; P=.027 ) . After multivariable analysis , higher plasma HIV-1 load ( odds ratio [ OR ] , 2.5 ; 95 % CI , 1.7 - 3.5 ; P < .001 ) , larger lesions ( OR , 2.5 ; 95 % CI , 1.5 - 4.1 ; P < .001 ) , purulent ulcers ( OR , 2.2 ; 95 % CI , 1.1 - 4.2 ; P < .02 ) , multiple ulcers ( > 5 ; OR , 3.6 ; 95 % CI , 1.6 - 8.4 ; P=.002 ) , and herpes seropositivity ( OR , 3.4 ; 95 % CI , 1.7 - 7.0 ; P < .001 ) remained associated with increased odds of HIV-1 lesional shedding . Ulcers associated with herpes simplex virus type 2 infection were less likely to shed ( OR , 0.6 ; 95 % CI , 0.3 - 1.0 ; P = .05 ) , compared with ulcers with unknown etiology . CONCLUSIONS HIV-positive men should be screened and treated for GUD to minimize HIV shedding and transmission to uninfected sexual partners |
13,819 | 26,171,993 | BACKGROUND There is good evidence that combining two different analgesics in fixed doses in a single tablet can provide better pain relief in acute pain and headache than either drug alone , and that the drug-specific benefits are essentially additive .
These values were close to those predicted by published models for combination analgesics in acute pain , and were supported by low ( good ) NNT values for prevention of remedication .
For ibuprofen 200 mg + caffeine 100 mg particularly , the low NNT value is among the lowest ( best ) values for analgesics in this pain model .
In principle , this can deliver good analgesia at lower doses of ibuprofen | This appears to be broadly true in postoperative pain and migraine headache across a range of different drug combinations , and when tested in the same and different trials .
Adding caffeine to analgesics also increases the number of people obtaining good pain relief .
Combinations of ibuprofen and caffeine are available without prescription in some parts of the world .
OBJECTIVES To assess the analgesic efficacy and adverse effects of a single oral dose of ibuprofen plus caffeine for moderate to severe postoperative pain , using methods that permit comparison with other analgesics evaluated in st and ardised trials using almost identical methods and outcomes . | BACKGROUND Combination therapy has been widely used for the clinical management of acute pain . By combining 2 drugs with different mechanisms of action , such therapy provides additive analgesic effects while reducing the risk for adverse effects . OBJECTIVE This study compared the efficacy and tolerability of oxycodone 5 mg/ibuprofen 400 mg with those of oxycodone 5 mg/acetaminophen 325 mg , hydrocodone 7.5 mg/acetaminophen 500 mg , and placebo in a dental pain model . METHODS This was a multicenter , r and omized , double-blind , placebo- and active-controlled , parallel-group , single-dose study in patients experiencing moderate to severe pain after surgical removal of > or = 2 ipsilateral impacted third molars . Patients were r and omly assigned to receive oxycodone 5 mg/ibuprofen 400 mg , oxycodone 5 mg/acetaminophen 325 mg , hydrocodone 7.5 mg/acetaminophen 500 mg , or placebo . The primary outcome measures were total pain relief through 6 hours after dosing ( TOTPAR6 ) , sum of pain intensity differences through 6 hours ( SPID6 ) , and adverse events . Secondary efficacy measures included SPID3 and TOTPAR3 , peak pain relief , peak pain intensity difference , time to onset of pain relief , time to use of rescue medication , proportion of patients reporting pain half gone , and the patient 's global evaluation . RESULTS Two hundred forty-nine patients ( 43.5 % male ; 87.5 % white ; mean age , 19.1 years ; mean body weight , 153.6 pounds ) were r and omized to treatment as follows : 62 to oxycodone 5 mg/ibuprofen 400 mg , 61 to oxycodone 5 mg/acetaminophen 325 mg , 63 to hydrocodone 7.5 mg/acetaminophen 500 mg , and 63 to placebo . Oxycodone 5 mg/ibuprofen 400 mg provided significantly greater analgesia compared with oxycodone 5 mg/acetaminophen 325 mg , hydrocodone 7.5 mg/acetaminophen 500 mg , and placebo ( mean [ SD ] TOTPAR6 , 14.98 [ 5.37 ] , 9.53 [ 6.77 ] , 8.36 [ 6.68 ] , and 5.05 [ 6.49 ] , respectively ; P < 0.001 , oxycodone 5 mg/ibuprofen 400 mg vs all other treatments ) . SPID6 values also differed significantly for oxycodone 5 mg/ibuprofen 400 mg compared with all other treatments ( mean : 7.78 [ 4.11 ] , 3.58 [ 4.64 ] , 3.32 [ 4.73 ] , and 0.69 [ 4.85 ] ; P < 0.001 ) . Oxycodone 5 mg/ibuprofen 400 mg was significantly more effective compared with the other treatments on all secondary end points ( P < 0.001 , all variables except peak PID vs oxycodone 5 mg/acetaminophen 325 mg [ P = 0.006 ] ) , with the exception of the time to onset of analgesia . The lowest frequency of nausea and vomiting occurred in the groups that received oxycodone 5 mg/ibuprofen 400 mg ( 6.5 % and 3.2 % , respectively ) and placebo ( 3.2 % and 1.6 % ) . Rates of nausea and vomiting were significantly lower with oxycodone 5 mg/ibuprofen 400 mg compared with oxycodone 5 mg/acetaminophen 325 mg ( P = 0.011 and P = 0.009 , respectively ) but not with hydrocodone 7.5 mg/acetaminophen 500 mg . CONCLUSIONS In this study in patients with moderate to severe pain after surgery to remove impacted third molars , oxycodone 5 mg/ibuprofen 400 mg provided significantly better analgesia throughout the 6-hour study compared with the other opioid/nonopioid combinations tested , and was associated with fewer adverse events 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 & NA ; There is uncertainty over whether the patient group in which acute pain studies are conducted ( pain model ) has any influence on the estimate of analgesic efficacy . Data from four recently up date d systematic review s of aspirin 600/650 mg , paracetamol 600/650 mg , paracetamol 1000 mg and ibuprofen 400 mg were used to investigate the influence of pain model . Area under the pain relief versus time curve equivalent to at least 50 % maximum pain relief over 6 h was used as the outcome measure . Event rates with treatment and placebo , and relative benefit ( RB ) and number needed to treat ( NNT ) were used as outputs from the meta‐analyses . The event rate with placebo was systematic ally statistically lower for dental than postsurgical pain for all four treatments . Event rates with analgesics , RB and NNT were infrequently different between the pain models . Systematic difference in the estimate of analgesic efficacy between dental and postsurgical pain models remains unproven , and , on balance , no major difference is likely In a double-blind , single dose study of analgesic efficacy , 165 patients who were expected to develop moderate to severe pain following the removal of an impacted m and ibular third molar tooth were allocated to receive aspirin , placebo , or an increasing dose of a fixed ratio ibuprofen/codeine combination . The degree of pain experienced prior to medication was noted and the patients were asked to record the degree of pain and of pain relief hourly for the following 5 hours . The study produced clear evidence of the superior efficacy of the combinations when compared to placebo and aspirin . In addition , the high dose combination appeared to be superior with respect to pain relief and the need for additional analgesia compared to the low dose treatment . There were few side effects and only one severe reaction was reported by a patient in the high dose group . To avoid side effects it is suggested that the medium-dose combination , ibuprofen 400 mg/codeine 30 mg , is optimal In a double-blind , single dose study of analgesic efficacy , 202 patients who had undergone lower 3rd molar extraction were divided into 5 groups to receive aspirin , placebo , ibuprofen , codeine , or an ibuprofen/codeine combination . Ibuprofen 200 mg ( with or without codeine phosphate 15 mg ) and aspirin 600 mg were significantly superior to either placebo or codeine phosphate 15 mg alone . Codeine phosphate at a dose of 15 mg was ineffective as an analgesic either alone or in combination Background Previous analysis of a single data set in acute pain following third molar extraction demonstrated a strong relationship between the speed of reduction of pain intensity and overall pain relief , as well as need for additional analgesia . Methods Individual patient data analysis of a single r and omized , double-blind trial of placebo , paracetamol 1000 mg , ibuprofen sodium 400 mg and ibuprofen-poloxamer 400 mg following third molar extraction . Visual analogue scale pain intensity ( VASPI ) and other measurements were made at baseline , every 5–45 min , and at 60 , 90 , 120 , 180 , 240 , 300 and 360 min . Results Most patients produced consistent VASPI results over time . For placebo and paracetamol , few patients achieved low VASPI scores and maintained them . For both ibuprofen formulations , VASPI scores fell rapidly during the first hour and were then typically maintained until later re-medication . Analysis of all patients showed that rapid VASPI reduction in the first hour was strongly correlated with good overall pain relief ( high total pain relief over 0–6 h ) , and with lesser need for additional analgesia within 6 h. Results for this analysis were in very good agreement with a previous analysis , validating the relationship between fast initial pain intensity reduction and overall good pain relief in this setting . Conclusions In acute pain following third molar extraction , faster acting analgesic formulations provide earlier onset of pain relief , better overall pain relief and a less frequent need for additional analgesia , indicating longer lasting pain relief Non-steroidal anti-inflammatory analgesics are commonly prescribed to out- patients who have undergone oral surgical procedures , since they are said to provide excellent pain relief for mild to moderate pain , allied with minimal side-effects . One hundred patients were entered into a r and omised clinical trial to compare the efficacy of a simple non-steroidal analgesic with that of a combination analgesic compound following the removal of lower third molars under local anaesthesia . Pain scores were measured for patients post-operatively by means of a verbal rating scale for 3 days and data were analysed using the Mann-Whitney U-test . Results suggest that this combination product offers no advantages ( but shows definite disadvantages ) when compared to an effective non-steroidal anti-inflammatory In a r and omised , double‐blind , double‐dummy , multiple dose , crossover study in 30 patients we compared an ibuprofen/codeine combination ( 400 mg ibuprofen/25.6 mg codeine phosphate ) with a paracetamol/codeine/caffeine combination ( 1 g paracetamol/ 16 mg codeine phosphate/60 mg caffeine ) for pain relief over 6 days after two‐stage bilateral lower third molar removal . The ibuprofen combination produced significantly greater analgesia than the paracetamol combination , both on single‐dose analysis of the first and second days and on multiple‐dose measures for days 1 , 2 , 3 and 4 . The mean incidence of adverse effects over the 6 days was 20 % for both combinations . This trial design ( crossover with multiple dosing in out patients ) is a sensitive way of testing for analgesia , and is potentially more predictive of adverse effect problems than single‐dose studies . It confirms that multiple dosing may show increased efficacy Abstract A previously established relationship for deriving dichotomous from continuous information in r and omised controlled trials ( RCTs ) of analgesics has been tested using an independent data set . Individual patient information from 18 RCTs of parallel‐group design in acute postoperative pain ( after abdominal , gynaecological and oral surgery ) was used to calculate the percentage of the maximum possible pain relief score ( % maxTOTPAR ) and the proportion of patients with > 50%maxTOTPAR for the different treatments . The relationship between the measures was investigated in 85 treatments with over 3400 patients . In 80 of 85 treatments ( 94 % ) agreement between calculated and actual number of patients with > 50%maxTOTPAR was within four patients per treatment and in 72 ( 85 % ) was within three ( average of 40 patients per treatment , range 21–58 patients ) . Summing the positive and negative differences between actual and calculated numbers of patients with > 50%maxTOTPAR gave an average difference of 0.30 patients per treatment arm . Reports of RCTs of analgesics frequently describe results of studies in the form of mean derived indices , rather than using discontinuous events , such as number or proportion of patients with 50 % pain relief . Because mean data inadequately describe information with a non‐normal distribution , combining mean data in systematic review s may compromise the results . Showing that dichotomous data can reliably be derived from mean data in acute pain studies enables data published as means to be used for quantitative systematic review s which require data in dichotomous form BACKGROUND Ketorolac is approved for the relief of postoperative pain but concerns have been raised over a possible risk of serious adverse effects and death . Two regulatory review s in Europe on the safety of ketorolac found the data were inconclusive and lacked comparison with other non-steroidal anti-inflammatory drugs . The aim of this study was to compare the risk of serious adverse effects with ketorolac vs diclofenac or ketoprofen in adult patients after elective major surgery . METHODS This prospect i ve , r and omized multicentre trial evaluated the risks of death , increased surgical site bleeding , gastrointestinal bleeding , acute renal failure , and allergic reactions , with ketorolac vs diclofenac or ketoprofen administered according to their approved parenteral and oral dose and duration of treatment . Patients were followed for 30 days after surgery . RESULTS A total of 11,245 patients completed the trial at 49 European hospitals . Of these , 5634 patients received ketorolac and 5611 patients received one of the comparators . 155 patients ( 1.38 % ) had a serious adverse outcome , with 19 deaths ( 0 . 17 % ) , 117 patients with surgical site bleeding ( 1.04 % ) , 12 patients with allergic reactions ( 0.12 % ) , 10 patients with acute renal failure ( 0.09 % ) , and four patients with gastrointestinal bleeding ( 0.04 % ) . There were no differences between ketorolac and ketoprofen or diclofenac . Postoperative anticoagulants increased the risk of surgical site bleeding equally with ketorolac ( odds ratio=2.65 , 95 % CI=1.51 - 4.67 ) and the comparators ( odds ratio=3.58 , 95 % CI=1.93 - 6.70 ) . Other risk factors for serious adverse outcomes were age , ASA score , and some types of surgery ( plastic/ear , nose and throat , gynaecology , and urology ) . CONCLUSION We conclude that ketorolac is as safe as ketoprofen and diclofenac for the treatment of pain after major surgery OBJECTIVE To investigate morbidity related to misuse of over-the-counter ( OTC ) codeine-ibuprofen analgesics . DESIGN AND SETTING Prospect i ve case series collected from Victorian hospital-based addiction medicine specialists between May 2005 and December 2008 . MAIN OUTCOME MEASURES Morbidity associated with codeine-ibuprofen misuse . RESULTS Twenty-seven patients with serious morbidity were included , mainly with gastrointestinal haemorrhage and opioid dependence . The patients were taking mean daily doses of 435 - 602 mg of codeine phosphate and 6800 - 9400 mg ibuprofen . Most patients had no previous history of substance use disorder . The main treatment was opioid substitution treatment with buprenorphine-naloxone or methadone . CONCLUSIONS Although codeine can be considered a relatively weak opioid analgesic , it is nevertheless addictive , and the significant morbidity and specific patient characteristics associated with overuse of codeine-ibuprofen analgesics support further awareness , investigation and monitoring of OTC codeine-ibuprofen analgesic use & NA ; Reports of RCTs of analgesics frequently describe results of studies in the form of mean derived indices , rather than using discontinuous events — such as number or proportion of patients with 50 % pain relief . Because mean data inadequately describe information with a non‐normal distribution , combining mean data in systematic review s may compromise the results . Showing that dichotomous data can reliably be derived from mean data , at least in acute pain models , indicates that more meaningful overviews or meta‐ analysis may be possible . This study investigated the relationship between continuous and dichotomous analgesic measures in a set of individual patient data , and then used that relationship to derive dichotomous from continuous information in r and omised controlled trials ( RCTs ) of analgesics . Individual patient information from 13 RCTs of parallel‐group and crossover design in acute postoperative pain was used to calculate the percentage of the maximum possible pain relief score ( % maxTOTPAR ) and the proportion of patients with greater than 50 % pain relief ( > 50%maxTOTPAR ) for the different treatments . The relationship between the measures was investigated in 45 actual treatments and 10 000 treatments simulated using the underlying actual distribution ; 1283 patients had 45 separate treatments . Mean % maxTOTPAR correlated with the proportion of patients with > 50%maxTOTPAR ( r2 = 0.90 ) . The relationship calculated from all the 45 treatments predicted to within three patients the number of patients with more than 50 % pain relief in 42 of 45 treatments , and 98.8 % of 10 000 simulated treatments . For seven effective treatments , actual numbers‐needed‐to‐treat ( NNT ) to achieve > 50%maxTOTPAR compared with placebo were very similar to those derived from calculated data Recent studies have demonstrated that caffeine acts as an analgesic adjuvant when combined with acetaminophen , aspirin , or their mixture . Our objective was to determine whether similar enhancement of analgesia could be demonstrated when caffeine is combined with ibuprofen . On a double‐blind basis , a single oral dose of ibuprofen ( 50 , 100 , or 200 mg ) , a combination of ibuprofen , 100 mg , with caffeine , 100 mg , a combination of ibuprofen , 200 mg , with caffeine , 100 mg , or placebo was r and omly assigned to 298 out patients with postoperative pain after the surgical removal of impacted third molars . With a self‐rating record , subjects rated their pain and its relief hourly for 8 hours . All active treatments were significantly superior to placebo , and the caffeine effect was significant for every measure of analgesia . Relative potency estimates indicated that the combination was 2.4 to 2.8 times as potent as ibuprofen alone . The combination also had a more rapid onset and longer duration of analgesic action . The analgesic adjuvancy of caffeine clearly extends to combinations with nonsteroidal anti‐inflammatory drugs other than acetaminophen or aspirin The effectiveness of caffeine as an adjuvant to ibuprofen has been documented in investigations of acute pain . Our objectives were to assess this agent in the treatment of tension‐type headache and to establish clinical trial methods capable of assessing this agent in comparison with various tension headache treatments . Stopwatch technology was used for measurement techniques & NA ; A combination of 20 mg codeine base and ibuprofen 400 mg was compared with ibuprofen 400 mg in a r and omised double‐blind cross‐over study of multiple doses in 25 patients after 2‐stage bilateral third molar removal . The combination produced significantly greater pain relief and doubled the hours of minimum pain intensity and maximal relief on the day of surgery . The patients rated the combination significantly better than ibuprofen alone , and the combination was preferred by 16 of the 22 patients expressing a preference . There was no significant increase in side‐effect incidence with the combination . The 30 % increase in analgesic effect may be of clinical benefit , and this trial design , cross‐over with multiple dosing in out‐ patients , may be a sensitive test for analgesics , potentially more predictive of side‐effect problems than single‐dose studies A double-blind r and omized crossover analgesic trial was carried out on 70 patients undergoing surgical removal of one lower third molar at each visit . The analgesic efficacy of a two-dose regimen of the combination ibuprofen-codeine , 400 to 60 mg , was compared with ibuprofen , 400 mg . Each of the two doses was taken when the patient needed pain relief and the pain intensity was measured on a visual analog scale during the 10-hour period after the first medication . Because of carryover effects between periods 1 and 2 , the analysis was carried out only for period 1 according to a parallel group design . Of the 60 patients who were evaluated for analgesic effect , the mean pain reduction of dose 1 was 63 % for the 29 patients given ibuprofen-codeine and 50 % for the 31 patients given ibuprofen ; the mean duration of effect was 7.5 and 6.3 hours , respectively . The difference in pain reduction index ( pain reduction X duration of effect ) between the two treatments was significant in favor of the combination , whereas the separate variables of pain reduction and duration of effect were not significantly different . The mean pain reduction was 67 % after doses 1 and 2 for patients on ibuprofen-codeine and 52 % for those on ibuprofen ; the mean duration of effect was 9.4 and 9.2 hours , respectively . For doses 1 and 2 , the difference in pain reduction index per dose between the two treatments was significant but not the difference for the separate variables , pain reduction , and duration of effect . ( ABSTRACT TRUNCATED AT 250 WORDS Objectives : To compare the relative merits of single doses of ibuprofen and ibuprofen plus caffeine in the treatment of pain after third molar removal . Design : R and omised , double‐blind , placebo‐controlled , single‐dose parallel‐group comparison of placebo , ibuprofen 200 and 400 mg with ibuprofen 200 mg plus 50 , 100 or 200 mg of caffeine . Subjects : 161 patients undergoing lower third molar removal . Results : All active treatments produced significant analgesia and mood elevation compared with placebo . There was no significant difference in the effects of 200 and 400 mg of ibuprofen . Adding caffeine to 200 mg ibuprofen produced significantly more analgesic effect at 45 and 60 min than ibuprofen 200 mg alone . Ten patients reported 11 adverse effects , none in the highest caffeine dose group . Conclusions : Caffeine increased the analgesic effect of ibuprofen 200 mg , through an earlier onset of analgesic effect . This was achieved in this single dose context without problematic adverse effects Summary A double-blind , r and omised analgesic trial was carried out in 165 patients undergoing surgical removal of one impacted lower wisdom tooth . In a two-dose regimen , the analgesic efficacy of the combination ibuprofen-codeine 200 mg : 30 mg was compared with that of acetylsalicylic acid-codeine 500 mg : 30 mg and codeine 30 mg . Each dose was taken when the patient needed pain relief . The intensity of the pain was measured on a visual analogue scale during the 10-h period after the first dose . The mean pain reduction by Dose 1 in patients on ibuprofen-codeine , acetylsalicylic acid-codeine and codeine was 64 % , 45 % and 26 % , respectively , and the mean duration of effect was 8.3 , 6.3 and 5.6 h. According to the pain reduction , duration of effect and pain reduction index after Doses 1 and 1 + 2 . there was a significant difference between ibuprofen-codeine and the other two drugs . The maximum pain reduction within 4 hours was 84 % with ibuprofen-codeine . This was significantly different from the reduction achieved both with acetylsalicylic acid-codeine ( 64 % ) and codeine ( 35 % ) . Seventeen patients reported adverse events : 5 on ibuprofen-codeine , 4 on acetylsalicylic acid-codeine and 8 on codeine . The most common events were tiredness and vertigo . It is concluded that the combination ibuprofen-codeine 200 mg : 30 mg had greater analgesic efficacy compared to the combination acetylsalicylic acid-codeine 500 mg : 30 or codeine 30 mg in patients with pain after removal of the lower third molars Our purpose was to compare the analgesic efficacy and safety of single oral doses of the combination of ibuprofen 400 mg plus codeine 60 mg and the combination of ibuprofen 200 mg plus codeine 30 mg with ibuprofen 400 mg alone , codeine sulfate 60 mg alone , and placebo . One hundred ninety‐five patients with severe pain result ing from episiotomy , cesarean section , or gynecologic surgery completed a r and omized , double‐blind , stratified , parallel‐group study . Patients were observed during a 4‐hour period after medication . Based on the sum of the pain intensity differences ( SPID ) , total pain relief ( TOTPAR ) , and most of the hourly direct measures of pain and relief , both doses of the combination and ibuprofen 400 mg alone were statistically superior to placebo . Codeine 60 mg was statistically superior to placebo based on TOTPAR , the global ratings , and a few hourly measures . The mean effect of the combination of ibuprofen 400 mg plus codeine 60 mg was significantly superior to the mean effect of ibuprofen 400 mg alone ½ , 1 , and 2 hours after medication and to the mean effect of ibuprofen 400 mg alone and codeine 60 mg alone for SPID , TOTPAR , and other measures as well . The low‐dose combination was significantly more effective than codeine 60 mg for a few hourly measures but was not significantly superior to ibuprofen 400 mg . Based on these findings it appears that the combination of ibuprofen 400 mg plus codeine 60 mg , particularly in the first few hours after medication , is more efficacious than its constituents In a double-blind single-dose study , the analgesic effect of a new ibuprofen-codeine phosphate combination was compared with those of codeine phosphate alone and placebo for the relief of moderate and severe postepisiotomy pain . In the 113 patients studied , combination therapy was superior to codeine phosphate alone and to placebo , the difference between the combination and codeine phosphate alone reaching statistical significance ( P less than 0.05 ) after two hours . The few side effects reported were not of a serious nature BACKGROUND The sensation of pain arises from both central and peripheral sites , and inflammation may be one of its underlying causes . Combination therapy with analgesic agents having multimodal mechanisms of action and complementary pharmacokinetic properties enhances pain relief by addressing the different pathways of pain while limiting individual drug doses and , therefore , the potential for adverse effects caused by any single agent . Oxycodone and ibuprofen each have been used effectively as monotherapy and in other combinations for the treatment of acute pain ; a fixed combination of these analgesics may improve pain relief in the setting of abdominal or pelvic surgery , where trauma and any result ant inflammation may be present at the same time . OBJECTIVE This study evaluated and compared the analgesic efficacy and tolerability of a single-dose combination tablet containing oxycodone 5 mg/ibuprofen 400 mg with either agent alone and with placebo in women who had undergone abdominal or pelvic surgery . METHODS In this multicenter , r and omized , double-blind , placebo- and active-controlled , parallel-group trial , women experiencing moderate to severe pain between 14 and 48 hours after surgery were r and omized per protocol to receive a single dose of study medication in a 3:3:1:1 ratio ( combination oxycodone/ibuprofen , ibuprofen , oxycodone , and placebo , in that order ) . Over a 6-hour study period , patients recorded their assessment s of pain intensity ( 100-mm visual analog scale and 4-point scale ) , relief from starting pain , and overall evaluation of study drug based on prespecified definitions and rating scales . Based on these data , the following primary efficacy end points were determined : total pain relief 6 hours after dosing ( TOTPAR6 ) and sum of pain intensity differences 6 hours after dosing ( SPID6 ) . Other end points included the time to onset of pain relief , time to use of rescue medication , and patient 's global rating of analgesic effectiveness . Tolerability was evaluated on the basis of observed and patient-reported adverse events and findings on physical examination . RESULTS Four hundred fifty-six women participated in the study . They were primarily white and had a mean age of 41.6 years and a mean body weight of 171.5 pounds . Combination treatment was associated with significantly better TOTPAR6 and SPID6 scores compared with ibuprofen alone ( P < 0.02 and P < 0.015 , respectively ) , oxycodone alone ( P < 0.009 and P < 0.001 ) , or placebo ( both , P < 0.001 ) . Fewer patients receiving combination treatment required rescue medication , and the time to use of rescue medication was significantly longer in the combination-treatment group compared with the other groups ( P < 0.05 ) . Patients ' global ratings of analgesic efficacy were significantly higher in the combination-treatment group compared with all other groups ( P < 0.044 vs ibuprofen alone ; P < 0.001 vs oxycodone alone and placebo ) . The onset of pain relief occurred within 15 minutes of dosing with all 4 regimens . Nausea was the most frequently reported treatment-emergent adverse event in all 4 groups . The incidence of treatment-emergent adverse events was highest with placebo ( 55.0 % ) , followed by oxycodone alone ( 44.2 % ) , ibuprofen alone ( 42.3 % ) , and combination treatment ( 40.8 % ) . CONCLUSIONS In this population of women who had undergone abdominal or pelvic surgery , the combination of oxycodone 5 mg/ibuprofen 400 mg was significantly more effective than either agent alone or placebo in the treatment of moderate to severe postoperative pain In a double-blind , single-dose study , the analgesic effect of a combined ibuprofen-codeine phosphate preparation was compared with those of zomepirac and placebo in 127 patients with moderate or severe postepisiotomy pain . Both the combination and zomepirac were significantly more effective than placebo for up to six hours , but the onset of action of the combination was more rapid than that of zomepirac . The study was notable for the virtual absence of side effects & 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 Subjects who had undergone dental impaction surgery and who had moderate to severe postoperative pain were given , under double-blind , r and omized conditions , a single dose of either codeine 60 mg , aspirin 650 mg , ibuprofen 400 mg , aspirin 650 mg + codeine 60 mg , ibuprofen 400 mg + codeine 60 mg , or placebo . A total of 249 subjects were included in the statistical analysis . On a report form , subjects recorded pain intensity , pain relief , and side effects hourly for four hours . They also gave an overall impression at the end of the observation period . Analysis of variance and pairwise contrasts were used to analyze the data . For the sum of pain intensity differences , the total of the hourly pain relief scores , and overall impression , there was a significant analgesic effect for codeine , aspirin , and ibuprofen and no significant interaction when they were used in combination . Ibuprofen alone was statistically superior to aspirin and also achieved higher mean scores than the aspirin-codeine combination . The ibuprofen-codeine combination was the most effective treatment for every analgesic parameter , but it was not statistically superior to ibuprofen alone . The possibility exists that the ibuprofen-codeine combination peaked out the sensitivity of the model . There was no notable difference in the frequency or intensity of side effects among the treatment groups , and no subject had to withdraw due to an adverse effect . This study again confirms the superiority of ibuprofen to aspirin and suggests that ibuprofen is at least as effective as an aspirin-codeine combination . Codeine added a small amount of additional analgesia when used in combination with ibuprofen Abstract One way to ensure adequate sensitivity for analgesic trials is to test the intervention on patients who have established pain of moderate to severe intensity . The usual criterion is at least moderate pain on a categorical pain intensity scale . When visual analogue scales ( VAS ) are the only pain measure in trials we need to know what point on a VAS represents moderate pain , so that these trials can be included in meta‐ analysis when baseline pain of at least moderate intensity is an inclusion criterion . To investigate this we used individual patient data from 1080 patients from r and omised controlled trials of various analgesics . Baseline pain was measured using a 4‐point categorical pain intensity scale and a pain intensity VAS under identical conditions . The distribution of the VAS scores was examined for 736 patients reporting moderate pain and for 344 reporting severe pain . The VAS scores corresponding to moderate or severe pain were also examined by gender . Baseline VAS scores recorded by patients reporting moderate pain were significantly different from those of patients reporting severe pain . Of the patients reporting moderate pain 85 % scored over 30 mm on the corresponding VAS , with a mean score of 49 mm . For those reporting severe pain 85 % scored over 54 mm with a mean score of 75 mm . There was no difference between the corresponding VAS scores of men and women . Our results indicate that if a patient records a baseline VAS score in excess of 30 mm they would probably have recorded at least moderate pain on a 4‐point categorical scale Thirty clinical studies involving more than 10,000 patients conducted during the last 20 years have been analyzed to assess the value of caffeine as an analgesic adjuvant . Although most studies included patients with postpartum uterine cramping or episiotomy pain , some involved patients with pain from oral surgery or headache . In 21 of 26 studies , the relative potency estimates of an analgesic with caffeine to an analgesic without caffeine is greater than one . The pooled relative potency estimates in each of several major categories of combination analgesics are significantly greater than one . The overall pooled relative potency estimate is 1.41 , with 95 % confidence limits of 1.23 to 1.63 ; that is , to obtain the same amount of response from an analgesic without caffeine requires a dose that is approximately 40 % greater than one with caffeine OBJECTIVE This study compared the efficacy and safety of a single dose of oxycodone 5 mg/ibuprofen 400 mg versus its individual components and placebo in a third-molar extraction model . METHODS In this multicenter , double-blind , double-dummy , parallel-group investigation , subjects with moderate to severe pain within 5 hours after extraction of > or = 2 ipsilateral bony impacted third molars were r and omized to single doses of oxycodone 5 mg/ibuprofen 400 mg , ibuprofen 400 mg , oxycodone 5 mg , or placebo . Primary efficacy variables were the sum of pain intensity difference over 6 hours ( SP1D6 ) and total pain relief through 6 hours ( TOTPAR6 ) . The pharmacokinetics of oxycodone and ibuprofen , alone and in combination , were also determined in a subset of patients . RESULTS A total of 498 subjects were r and omized to treatment ( 187 to oxycodone 5 mg/ibuprofen 400 mg , 186 to ibuprofen 400 mg , 63 to oxycodone 5 mg , and 62 to placebo ) . Baseline demographics were generally similar among treatment groups , despite differences in sex ( P = 0.041 ) and race ( P = 0.023 ) . Combination therapy was associated with greater analgesia than ibuprofen alone , oxycodone alone , or placebo ( mean [ SE ] TOTPAR6 : 13.3 [ 0.52 ] , 12.2 [ 0.52 ] , 4.3 [ 0.82 ] , and 4.2 [ 0.83 ] , respectively [ P < 0.001 vs oxycodone or placebo , P = 0.012 vs ibuprofen ] ; mean [ SE ] SP1D6 : 6.54 [ 0.42 ] , 5.41 [ 0.44 ] , 0.14 [ 0.60 ] , and 0.32 [ 0.59 ] , respectively [ P < 0.001 vs oxycodone or placebo , P = 0.002 vs ibuprofen ] ) . Combination therapy was well tolerated . Pharmacokinetic results implied no interaction between oxycodone and ibuprofen . CONCLUSIONS In this study , a single dose of oxycodone 5 mg/ibuprofen 400 mg was fast-acting , effective , and well tolerated in subjects with moderate to severe pain after dental surgery . Oxycodone 5 mg alone did not provide an efficacy benefit over placebo in this study & NA ; Combination analgesia is often recommended for the relief of severe pain . This was a double‐blind , 5‐arm , parallel‐group , placebo‐controlled , r and omised , single‐dose study design ed to compare the efficacy and tolerability of a novel single‐tablet combination of ibuprofen and paracetamol with that of an ibuprofen/codeine combination , and a paracetamol/codeine combination , using the dental impaction pain model . Subjects with at least 3 impacted third molars and experiencing moderate to severe postoperative pain were r and omised to receive : 1 or 2 tablets of a single‐tablet combination of ibuprofen 200 mg/paracetamol 500 mg ; 2 tablets of ibuprofen 200 mg/codeine 12.8 mg ; 2 tablets of paracetamol 500 mg/codeine 15 mg ; or placebo . Results for the primary endpoint , the sum of the mean scores of pain relief combined with pain intensity differences over 12 hours , demonstrated that 1 and 2 tablets of the single‐tablet combination of ibuprofen/paracetamol were statistically significantly more efficacious than 2 tablets of placebo ( P < 0.0001 ) and paracetamol/codeine ( P ⩽ 0.0001 ) ; furthermore , 2 tablets offered significantly superior pain relief to ibuprofen/codeine ( P = 0.0001 ) , and 1 tablet was found noninferior to this combination . Adverse events were uncommon during this study and treatment emergent adverse events were statistically significantly less frequent in the groups taking the ibuprofen/paracetamol combination compared with codeine combinations . In conclusion , 1 or 2 tablets of a single‐tablet combination of ibuprofen 200 mg/paracetamol 500 mg provided highly effective analgesia that was comparable with , or superior to , other combination analgesics currently indicated for strong pain . A single‐tablet combination of ibuprofen 200 mg/paracetamol 500 mg provides highly effective analgesia , comparable or superior to other combination analgesics indicated for strong pain |
13,820 | 28,757,301 | For a follow-up of up to 6 yr , active surveillance was found to have the lowest impact on cancer-specific QoL , surgery had a negative impact on urinary and sexual function when compared with active surveillance and EBRT , and EBRT had a negative impact on bowel function when compared with active surveillance and surgery .
This is the first systematic review comparing the impact of different primary treatments on cancer-specific QoL for men with clinical ly localised prostate cancer , using vali date d cancer-specific patient-reported outcome measures only .
PATIENT SUMMARY Our review of the current evidence suggests that for a period of up to 6 yr after treatment , men with localised prostate cancer who were managed with active surveillance reported high levels of quality of life ( QoL ) .
Men treated with surgery reported mainly urinary and sexual problems , while those treated with external beam radiotherapy reported mainly bowel problems .
Men eligible for brachytherapy reported urinary problems up to a year after therapy , but then their QoL returned gradually to as it was before treatment | CONTEXT Current evidence -based management for clinical ly localised prostate cancer includes active surveillance , surgery , external beam radiotherapy ( EBRT ) and brachytherapy .
The impact of these treatment modalities on quality of life ( QoL ) is uncertain .
OBJECTIVE To systematic ally review comparative studies investigating disease-specific QoL outcomes as assessed by vali date d cancer-specific patient-reported outcome measures with at least 1 yr of follow-up after primary treatment for clinical ly localised prostate cancer . | 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 . ) OBJECTIVES Establishing realistic health-related quality -of-life ( HRQOL ) expectations before the choice of cancer treatment is made is an important goal of patient counseling . We prospect ively studied the pretreatment expectations of prostate cancer-specific HRQOL with an adapted Exp and ed Prostate Cancer Index Composite instrument . METHODS Baseline pretreatment Exp and ed Prostate Cancer Index Composite scores , pretreatment expectation scores , and 1-year posttreatment scores were prospect ively collected for 50 patients undergoing radical prostatectomy or external beam radiotherapy . The pretreatment expectations and observed HRQOL scores at 1 year after treatment were compared for the urinary incontinence , urinary irritation , bowel , sexual , and hormonal domains . RESULTS The expectation scores did not differ from the HRQOL scores at 1 year for urinary irritation , bowel function , and the hormonal domain . However , the sexual domain expectations were 22.5 % greater than observed sexual domain scores 1 year after treatment ( P < 0.0001 , 99 % confidence interval 11 to 34 ) for both surgery and radiotherapy subjects . Anxiety , depression , education level , and income did not correlate with the expectations for HRQOL outcomes . A modest correlation was found between optimism and greater expectations for the sexual domain ( Pearson correlation coefficient 0.38 , P < 0.001 ) . CONCLUSIONS Measuring HRQOL expectations before treatment may eluci date discrepancies between patient expectations and observed outcomes . This pilot study found that patients ' expectations regarding urinary and bowel outcomes more closely reflected their eventual observed outcome than did their expectations regarding sexual outcome BACKGROUND Most localized prostate cancers are believed to have an indolent course . Within 15 yr of diagnosis , most deaths among men with prostate cancer ( PCa ) can be attributed to other competing causes . However , data from studies with extended follow-up are insufficient to determine appropriate treatment for men with localized disease . OBJECTIVE To investigate the long-term natural history of untreated , early-stage PCa . DESIGN , SETTING , AND PARTICIPANTS We conducted a population -based , prospect ive-cohort study using a consecutive sample of 223 patients with untreated , localized PCa from a regionally well-defined catchment area in central Sweden . All subjects were initially managed with observation . And rogen deprivation therapy was administered when symptomatic tumor progression occurred . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Based on > 30 yr of follow-up , the main outcome measures were : progression-free , cause-specific , and overall survival , and rates of progression and mortality per 1000 person-years . RESULTS AND LIMITATIONS After 32 yr of follow-up , all but 3 ( 1 % ) of the 223 men had died . We observed 90 ( 41.4 % ) local progression events and 41 ( 18.4 % ) cases of progression to distant metastasis . In total , 38 ( 17 % ) men died of PCa . Cause-specific survival decreased between 15 and 20 yr , but stabilized with further follow-up . All nine men with Gleason grade 8 - 10 disease died within the first 10 yr of follow-up , five ( 55 % ) from PCa . Survival for men with well-differentiated , nonpalpable tumors declined slowly through 20 yr , and more rapidly between 20 and 25 yr ( from 75.2 % [ 95 % confidence interval , 48.4 - 89.3 ] to 25 % [ 95 % confidence interval , 22.0 - 72.5 ] ) . It is unclear whether these data are relevant for tumors detected by elevated prostate-specific antigen levels . CONCLUSIONS Although localized PCa most often has an indolent course , local progression and distant metastasis can develop over the long term , even among patients considered low risk at diagnosis 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 PURPOSE Earlier studies evaluating the effect on quality of life ( QoL ) of localized prostate cancer interventions included patients receiving adjuvant hormone therapy , which could have affected their outcomes . Our objective was to compare the QoL impact of the three most common primary treatments on patients who were not receiving adjuvant hormonal treatment . PATIENTS AND METHODS This was a prospect i ve study of 435 patients treated with radical prostatectomy , external-beam radiotherapy , or brachytherapy . QoL was assessed before and after treatment with the Short Form-36 and the Exp and ed Prostate Cancer Index Composite . Differences between groups were tested by analysis of variance . Distribution of outcome at 3 years was examined by stratifying according to baseline status . Generalized estimating equation models were constructed to assess the effect of treatment over time . RESULTS Compared with the brachytherapy group , the prostatectomy group showed greater deterioration on urinary incontinence and sexual scores but better urinary irritative-obstructive results ( -18.22 , -13.19 , and + 6.38 , respectively , at 3 years ; P < .001 ) . In patients with urinary irritative-obstructive symptoms at baseline , improvement was observed in 64 % of those treated with nerve-sparing radical prostatectomy . Higher bowel worsening ( -2.87 , P = .04 ) was observed in the external radiotherapy group , with 20 % of patients reporting bowel symptoms . CONCLUSION Radical prostatectomy caused urinary incontinence and sexual dysfunction but improved pre-existing urinary irritative-obstructive symptoms . External radiotherapy and brachytherapy caused urinary irritative-obstructive adverse effects and some sexual dysfunction . External radiotherapy also caused bowel adverse effects . Relevant differences between treatment groups persisted for up to 3 years of follow-up , although the difference in sexual adverse effects between brachytherapy and prostatectomy tended to decline over long-term follow-up . These results provide valuable information for clinical decision making PURPOSE The American College of Surgeons Oncology Group phase III Surgical Prostatectomy Versus Interstitial Radiation Intervention Trial comparing radical prostatectomy ( RP ) and brachytherapy ( BT ) closed after 2 years due to poor accrual . We report health-related quality of life ( HRQOL ) at a mean of 5.3 years for 168 trial-eligible men who either chose or were r and omly assigned to RP or BT following a multidisciplinary educational session . PATIENTS AND METHODS After initial lack of accrual , a multidisciplinary educational session was introduced for eligible patients . In all , 263 men attended 47 sessions . Of those , 34 consented to r and om assignment , 62 chose RP , and 94 chose BT . Five years later , these 190 men underwent HRQOL evaluation by using the cancer-specific 50-item Exp and ed Prostate Cancer Index Composite , the Short Form 12 Physical Component Score , and Short Form 12 Mental Component Score . Response rate was 88.4 % . The Wilcoxon rank sum test was used to compare summary scores between the two interventions . RESULTS Of 168 survey responders , 60.7 % had BT ( 9.5 % r and omly assigned ) and 39.3 % had RP ( 9.5 % r and omly assigned ) . Median age was 61.4 years for BT and 59.4 for RP ( P = .05 ) . Median follow-up was 5.2 years ( range , 3.2 to 6.5 years ) . For BT versus RP , there was no difference in bowel or hormonal domains , but men treated with BT scored better in urinary ( 91.8 v 88.1 ; P = .02 ) and sexual ( 52.5 v 39.2 ; P = .001 ) domains , and in patient satisfaction ( 93.6 v 76.9 ; P < .001 ) . CONCLUSION Although treatment allocation was r and om in only 19 % , all patients received identical information in a multidisciplinary setting before selecting RP , BT , or r and om assignment . HRQOL evaluated 3.2 to 6.5 years after treatment showed an advantage for BT in urinary and sexual domains and in patient satisfaction BACKGROUND AND PURPOSE The aim of the study was to compare quality of life after permanent I-125 brachytherapy ( BT ) and external beam radiotherapy ( EBRT ) for prostate cancer . MATERIAL S AND METHODS A group of 104 patients ( 52 in each group ) have been surveyed prospect ively before EBRT/BT ( time A ) , at the last day of EBRT ( 70.2 - 72.0 Gy ) or one month after BT ( time B ) , and a median time of 16 months after EBRT/BT ( time C ) using a vali date d question naire ( Exp and ed Prostate Cancer Index Composite ) . Pairs were matched according to the following criteria : age + /-5 years , prostate volume + /-10 cc , use of anti and rogens , and erectile function . RESULTS Urinary function/bother scores decreased significantly more after BT both at time B and time C. Bowel function/bother scores tended to be higher after BT , with a lower percentage of patients with painful bowel movements ( BT : 12%/27%/15 % ; EBRT : 19%/52%/35 % at time A/B/C ; p<0.05 for differences at times B/C ) and rectal bleeding ( BT : 12%/12%/12 % ; EBRT : 8%/14%/17 % ) . No difference concerning erectile dysfunction was found ( 67 % vs. 61 % with preserved erections firm enough for intercourse after BT vs. EBRT at time C ) . CONCLUSIONS BT was associated with higher urinary , but lower rectal toxicity . The risk of treatment-associated erectile dysfunction did not differ between these methods BACKGROUND We sought to identify determinants of health-related quality of life after primary treatment of prostate cancer and to measure the effects of such determinants on satisfaction with the outcome of treatment in patients and their spouses or partners . METHODS We prospect ively measured outcomes reported by 1201 patients and 625 spouses or partners at multiple centers before and after radical prostatectomy , brachytherapy , or external-beam radiotherapy . We evaluated factors that were associated with changes in quality of life within study groups and determined the effects on satisfaction with the treatment outcome . RESULTS Adjuvant hormone therapy was associated with worse outcomes across multiple quality -of-life domains among patients receiving brachytherapy or radiotherapy . Patients in the brachytherapy group reported having long-lasting urinary irritation , bowel and sexual symptoms , and transient problems with vitality or hormonal function . Adverse effects of prostatectomy on sexual function were mitigated by nerve-sparing procedures . After prostatectomy , urinary incontinence was observed , but urinary irritation and obstruction improved , particularly in patients with large prostates . No treatment-related deaths occurred ; serious adverse events were rare . Treatment-related symptoms were exacerbated by obesity , a large prostate size , a high prostate-specific antigen score , and older age . Black patients reported lower satisfaction with the degree of overall treatment outcomes . Changes in quality of life were significantly associated with the degree of outcome satisfaction among patients and their spouses or partners . CONCLUSIONS Each prostate-cancer treatment was associated with a distinct pattern of change in quality -of-life domains related to urinary , sexual , bowel , and hormonal function . These changes influenced satisfaction with treatment outcomes among patients and their spouses or partners BACKGROUND Few studies have reported on late declines and long-term health-related quality of life ( HRQOL ) after prostate cancer ( PCa ) treatment . OBJECTIVE We assessed long-term HRQOL following various treatments for localized PCa . DESIGN , SETTING , AND PARTICIPANTS This cohort study of HRQOL up to 10 yr after treatment used a prospect ively accrued , nationwide PCa registry that collects longitudinal patient-reported HRQOL . INTERVENTION Various primary treatments for localized PCa . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS The Medical Outcomes Studies 36-item Short Form and the University of California , Los Angeles , Prostate Cancer Index characterized physical function , mental health , and sexual , urinary , and bowel function and bother . Repeated measures mixed-model analysis assessed change in HRQOL by treatment over time , and logistic regression was used to measure the likelihood of a clinical ly significant decline in HRQOL . RESULTS AND LIMITATIONS Among 3294 men , 1139 ( 34 % ) underwent nerve-sparing radical prostatectomy ( NSRP ) , 860 ( 26 % ) underwent non-NSRP , 684 ( 21 % ) underwent brachytherapy , 386 ( 12 % ) underwent external beam radiotherapy , 161 ( 5 % ) underwent primary and rogen deprivation therapy , and 64 ( 2 % ) pursued watchful waiting/active surveillance . Median follow-up was 74 mo ( interquartile range : 50 - 102 ) . Most treatments result ed in early declines in HRQOL , with some recovery over the next 1 - 2 yr and a plateau in scores thereafter . Surgery had the largest impact on sexual function and bother and on urinary function , radiation had the strongest effect on bowel function , and and rogen deprivation therapy had the strongest effect on physical function . The main limitation was attrition among the cohort . CONCLUSIONS Although most men experience initial declines in HRQOL in the first 2 yr after treatment , there is little change from 3 to 10 yr and most differences between treatments attenuated over time . PATIENT SUMMARY Various treatments for prostate cancer result in a distinct constellation of adverse effects on health-related quality of life , which may have a long-term impact . These findings are helpful regarding shared decision making over choice of primary treatment PURPOSE We evaluated the impact of localized prostate cancer treatment on general , cancer specific and symptom domains of quality of life for up to 5 years after diagnosis . MATERIAL S AND METHODS A total of 842 men from the Health Professionals Followup Study , diagnosed between 1993 and 1998 , were included in cross-sectional analyses of quality of life associated with prostate cancer treatment . A subset of 146 men diagnosed after 1995 were followed prospect ively . Quality of life was assessed with the Medical Outcomes Study Short-Form 36 Health Status Survey , Cancer Rehabilitation Evaluation System Short Form and University of California Los Angeles Prostate Cancer Index by mailed question naires . Primary treatment modality was taken from medical records and patient self-report . RESULTS Significant treatment differences were observed in all quality of life measures , with the largest occurring in sexual , urinary and bowel symptoms . Bowel function was significantly worse in patients who received external radiation and brachytherapy compared with prostatectomy ( p < 0.05 ) . Although they had better or equivalent urinary and sexual function ( p < 0.05 ) , patients treated with external radiation , hormones or watchful waiting had lower generic quality of life scores in multiple domains compared with those who underwent prostatectomy . Patients who had brachytherapy had similar generic quality of life outcomes compared with prostatectomy in all domains . CONCLUSIONS Our findings suggest that important differences in quality of life go beyond known physical symptoms associated with various prostate cancer treatment options , many of which involve making a trade-off . It is important for patients with prostate cancer and health care providers to consider these differences while making treatment decisions Objectives To compare the oncological and functional outcomes reported after radical retropubic prostatectomy ( RRP ) versus brachytherapy ( BT ) in the treatment of low-risk prostatic cancer ( CaP ) . Methods Between May 1999 and October 2002 , 200 patients ( mean age 65.3 ± 8.7 ) were enrolled and r and omized into two groups of 100 patients each to undergo RRP ( group 1 ) or BT ( group 2).Prior to and following treatment , all patients were evaluated by physical examination , PSA assay and compilation of IPSS , IIEF-5 and EORTC-QLQ-C30/PR25 question naires . Oncological results were reported at 5 years , while functional outcomes were reported at 6 months , and 1 and 5 years mean follow-up . Results Of the 200 patients studied , 174 completed the 5-year follow-up assessment . With regards to oncological outcomes , similar 5-year biochemical disease-free survival rates were reported for RRP ( 91.0 % ) or BT ( 91.7 % ) . At 6 months and 1 year , both techniques produced a significant decrease in quality of life aspects , while group 2 patients reported a significantly higher and longer lasting rate of urinary irritative disorders and better erective function than group 1 . No differences in functional outcomes were encountered after 5 years in either group . Conclusions RRP and BT are two different options for the treatment of low-risk CaP , which produce different short-term sequelae in terms of urinary disorders and erective functions , but similar biochemical disease-free survival . Further studies with a higher number of patients and a longer follow-up are needed to evaluate their comparative effectiveness on overall disease-specific survival and metastatic disease 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 Background . Quality -of-life outcomes are an important consideration for patients evaluating therapeutic options for localized prostate cancer . Objectives .The objective of this study was to describe the effect of treatment choice on change in health-related quality of life ( HRQOL ) among men with clinical ly localized prostate cancer . Research Design .This was a prospect i ve observational study . Subjects . The study subjects were 122 men with clinical ly localized adenocarcinoma of the prostate . Forty-two subjects ( 34 % ) underwent radical prostatectomy , 51 ( 42 % ) underwent radiation therapy , and 29 ( 24 % ) were followed with e-pectant management . Measures .The University of California at Los Angeles Prostate Cancer Quality of Life Inde- and the Medical Outcomes Study Short Form-36 were administered before and 3 and 12 months after initial treatment . The study used an analysis of covariance model adjusted for baseline differences in clinical and demographic factors . Results .Men who underwent radical prostatectomy e-perienced significant declines in urinary and se-ual function and bother that persisted at 12 months after treatment . Men treated with radiation therapy e-perienced smaller but significant declines in se-ual function and a decline in social function . E-pectant management patients did not have a significant change in disease-targeted or generic HRQOL domains . Differential rates of change in urinary and se-ual function between treatment groups persisted after adjustment for differences in pretreatment clinical and demographic factors . Conclusions .Men undergoing radical prostatectomy have substantial declines in urinary and se-ual function , and men undergoing radiotherapy have declines in se-ual function . Men undergoing e-pectant management have no change in disease-specific or general HRQOL in the first year after treatment 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 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 . ) |
13,821 | 32,276,823 | The risk of early loss in the IL group was higher than that in the DL group .
For removable prostheses and nonsplinted implants , DL was preferred .
The quality of scientific evidence significantly favors DL | STATEMENT OF PROBLEM The current trend is to shorten the loading times of dental implants .
However , information about the risk of early loss of implants that have been loaded immediately is scant if compared with data available for those conventionally loaded .
PURPOSE The purpose of this systematic review and meta- analysis was to study immediate ( IL ) and delayed loading ( DL ) protocol s in edentulous m and ibles to determine whether differences exist in implant success and crestal bone loss and to evaluate these possible differences in relation to the type of prosthesis and the splinting of the implants . | This study was design ed to compare the results of immediate and delayed loading of implants with implant-retained m and ibular overdentures . Ten patients ( test group ) received 40 Brånemark System MKII implants ( 4 per patient ) placed in the interforaminal area of the m and ible . St and ard abutments were immediately screwed to the implants , rigidly connected with a bar , and immediately loaded with an overdenture . Ten patients ( control group ) received the same type and number of implants in the same area , but the implants were left to heal submerged . Four to 8 months later , st and ard abutments were screwed to the implants and the same prosthetic procedure was applied . Each implant was evaluated at the time of prosthetic loading and at 6 , 12 , and 24 months after the initial prosthetic load with the following parameters : modified Plaque Index ( MPI ) , modified Bleeding Index ( MBI ) , probing depth ( PD ) , and Periotest . Peri-implant bone resorption was evaluated on panoramic radiographs taken 12 and 24 months after initial prosthetic loading . No significant differences were found between the 2 groups regarding MPI , MBI , Periotest , peri-implant bone resorption , and PD at 6 and 24 months ( P > .05 ) . The only difference was found regarding PD values on the mesial and lingual sites at 12 months ( P < .05 ) . The cumulative success rate of implants was 97.5 % in both groups . Results from this study showed that immediate loading of endosseous implants rigidly connected with a U-shaped bar does not seem to have any detrimental effect on osseointegration . Conversely , this method significantly shortens the duration of treatment with relevant satisfaction for the patients The aim of this 1-year study was to evaluate and compare crestal bone loss and clinical outcomes of immediate and delayed loaded implants supporting m and ibular overdentures with Locator attachments . In a r and omised controlled clinical trial , 36 completely edentulous patients ( mean age 59.6 years ) who desired to improve the stability of their m and ibular dentures were r and omly assigned into two groups . Each patient received two implants in the canine area of the m and ible after a minimal flap reflection . Implants were loaded by m and ibular overdentures either 3 months ( delayed loading group , G1 ) or the same day ( immediate loading group , G2 ) after implant placement . Locator attachments were used to retain all overdentures to the implants . Peri-implant vertical ( VBL ) and horizontal ( HBLO ) bone losses and clinical parameters [ plaque scores ( PI ) , gingival scores ( GI ) , probing depths ( PD ) and implant stability ( ISQ ) ] were assessed at time of overdenture insertion ( T0 ) , 6 months ( T6 ) and 12 months ( T12 ) after overdenture insertion . After 12 months of overdenture insertion , two implants ( 5.5 % ) failed in G2 . Vertical bone loss was significantly higher in G2 compared with G1 , while HBLO demonstrated insignificant differences between groups . All clinical parameters ( PI , GI , PD and ISQ ) did not differ significantly between groups . Vertical bone loss was significantly correlated with PD and HBLO . Immediately loaded two implants supporting a Locator-retained m and ibular overdenture are associated with more vertical bone resorption when compared to delayed loaded implants after 1 year . Clinical outcomes do not differ significantly between loading protocol 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 Objectives To appraise the feasibility of loading four implants with a pre-existing denture converted to a fixed dental prosthesis ( FDP ) on the day of implant surgery compared with waiting for 3- to 4-month healing . Methods Patients with an edentulous , fully healed m and ible were recruited in a faculty clinic to partake in a blinded two-arm parallel r and omized controlled trial ( RCT ) . The participants received four parallel intraforamina m and ibular implants with a moderately rough titanium surface ( Brånemark System Mk III or Mk IV TiUnite ; Nobel Biocare AB , Göteborg , Sweden ) . The implants were loaded on the same day by converting the participants ' pre-existing denture in the experimental group . The implants were placed using a one-stage surgery procedure , and the participants ' pre-existing denture were soft-relined in the control group . For both groups , the permanent 10- to 12-unit FDP consisting of a type-3 cast precious alloy veneered with acrylic and artificial teeth was placed 3–4 months after implant surgery . All participants have been recalled annually for 5 years for appraisal of bone loss and registration of adverse events . Results Thirty-five of the original 42 participants ( 83 % ) returned for clinical and radiological examinations at the 5-year follow-up recall . No selective dropout or specific reasons for dropout was identified in the two study arms ; leaving n = 17 ( Intention-to-treat group , ITT ) in the experimental group , alternatively n = 13 as per protocol group ( PP ) , and n = 18 participants in the control group ( ITT = PP ) . At study commencement , five of the participants assigned to the experimental group did not receive their planned intervention . In the control group , one implant failed to osseointegrate and another failed due to bone loss after 5 years . The crestal bone level changes over 5 years were identical in the experimental and control groups , that is , 1.2 mm ( SD = 0.7 ) . There were no differences between the two study arms with regard to incidence of biological and technical adverse events . Conclusions Implants in the anterior m and ible loaded immediately with a converted pre-existing denture appear to yield analogous clinical outcomes compared with waiting for 3–4 months over the first 5 years following implant surgery It was the aim of this 24-mo r and omized controlled clinical trial to investigate whether the survival of a single median implant placed in the edentulous m and ible to retain a complete denture is not compromised by immediate loading . Secondary outcomes were differences in prosthetic complications between the loading principles . Each of the 158 patients who received an implant was r and omly assigned to the immediate loading group ( n = 81 ) or the delayed loading group ( n = 77 ) . Recall visits were performed 1 mo after implant placement ( for only the delayed loading group ) and 1 , 4 , 12 , and 24 mo after implant loading . Nine implants failed in the immediate loading group , all within the first 3 mo of implant loading , and 1 implant failed in the delayed loading group prior to loading . Noninferiority of implant survival of the immediate loading group , as compared with the delayed loading group , could not be shown ( P = 0.81 ) . Consistent with this result , a secondary analysis with Fisher exact test revealed that the observed difference in implant survival between the treatment groups was indeed statistically significant ( P = 0.019 ) . The most frequent prosthetic complications and maintenance interventions in the m and ible were retention adjustments , denture fractures , pressure sores , and matrix exchanges . There was only 1 statistically significant difference between the groups regarding the parameter “ fracture of the denture base in the ball attachment area ” ( P = 0.007 ) . The results indicate that immediate loading of a single implant in the edentulous m and ible reveals inferior survival than that of delayed loading and therefore should be considered only in exceptional cases ( German Clinical Trials Register : DRKS00003730 ) BACKGROUND Implant-retained overdentures have become a st and ard option for the prosthetic treatment of the edentulous m and ible in the elderly . PURPOSE This prospect i ve study aim ed to compare immediate and conventional loading of four interforaminal implants supporting a Locator-retained m and ibular overdenture in elderly patients regarding implant survival , implant stability , and implant-related complications . MATERIAL AND METHODS The study population comprised 20 completely edentulous patients ( 11 males ) aged 60 years and older with severe m and ible resorption . Each patient received four interforaminal implants ( Neoss Ltd. , Harrogate , UK ) . Following r and omization , implants were loaded either immediately after dental implant surgery or 3 months after implant placement with the Locator-abutment system . At follow-up visits 3 , 6 12 , 24 , and 36 months after loading , implant stability was evaluated with Periotest and Ostell . RESULTS Twenty patients received 80 implants . In eight patients , 32 implants were loaded immediately . Two patients had to be switched from the immediate to the conventional loading group due to insufficient primary stability ( ≤30 Ncm ) . Implant survival was similar in both groups after 36 months . No implant was lost . Decreasing Periotest , and accordingly , increasing Ostell measurements indicated adequate osseointegration in both groups . The course of treatment was not significantly different in the two groups . There were comparable incidences of postoperative complaints like swelling , hematoma , or wound dehiscence , as well as need for prosthetic treatment due to abutment loosening or occlusal discrepancies . Incidence of pressure marks and number of patient visits were significantly higher in the conventional loading group . CONCLUSION With sufficient primary stability , immediate loading of four interforaminal implants in the edentulous m and ible might be the preferential choice in the elderly , reducing total treatment time , and number of patient visits PURPOSE A 1-year blinded two-arm parallel r and omized controlled clinical trial was conducted to test the null hypothesis that immediate loading of four dental implants between the mental foramina with a fixed prosthesis has no benefits compared with the conventional loading technique in terms of implant success and clinical function . MATERIAL S AND METHODS Forty-five patients , completely edentulous in the m and ibles seeking implant-supported prostheses at the Faculty of Dentistry , University of Toronto , were recruited . Four TiUnite dental implants ( NobelBiocare ® , Göteborg , Sweden ) were placed following the one-stage surgical protocol . Immediately after surgery , the patients were r and omly assigned to either study arms by a third independent party . In the experimental arm ( EA ) , existing m and ibular denture was converted into an interim implant-supported fixed bridge ( ISFB ) on the same day of surgery . In the control arm ( CA ) , the m and ibular denture was hollowed out and relined with a soft tissue reline . The implants were loaded with the permanent ISFB at least 3 months postsurgery . Patients were assessed by a calibrated independent investigator at 2 , 6 , and 12 months following completion of treatment . RESULTS A total of one hundred sixty implants were placed . Due to anatomical limitations , one patient was excluded from the study . Four patients in the EA did not receive intervention as allocated and were transferred to the CA . Implant success rate was comparable between the two arms and exceeded 96 % . Marginal bone loss was statistically significantly more in the immediate loading arm , -0.296 mm versus -0.037 mm ( intention to treat : p = .002 ; per protocol : p = .021 ) . The relatively early intervention and insertion of the final prosthesis in the immediate arm , when bone healing and remodeling process had not yet been completed , might explain the difference in the amount of bone loss . CONCLUSION Immediate loading of four dental implants with a fixed prosthesis in the edentulous m and ible is a feasible treatment option and leads to a substantial improvement in perceived oral health status OBJECTIVES The aim of this study was to evaluate and compare marginal bone loss and clinical outcomes of conventionally and immediately loaded two implants supporting a ball-retained m and ibular overdenture . MATERIAL S AND METHODS Thirty six completely edentulous patients ( 22 males and 14 females ) were r and omly assigned into two groups . Each patient received two implants in the canine area of the m and ible after a minimal flap reflection . Implants were loaded by m and ibular overdentures either 3 months ( conventional loading group ) or the same day ( immediate loading group ) after implant placement . Ball attachments were used to retain all overdentures to the implants . Vertical and horizontal alveolar bone losses were evaluated in both groups 1 and 3 years after implant placement using multislice computed tomography , which allow evaluation of peri-implant buccal and lingual alveolar bone . Plaque scores , gingival scores , probing depths and periotest values ( PTVs ) were evaluated at 4 months ( baseline ) , 1 and 3 years after implant placement . Clinical and radiographic evaluations were performed at distal , labial , mesial and lingual peri-implant sites . RESULTS After 3 years of follow-up period , the immediate loading group recorded significant vertical bone loss at distal and labial sites than the conventional loading group and no significant differences in horizontal bone loss between groups were observed . Probing depth at distal and labial sites in the immediate loading group were higher than the conventional loading group , while plaque scores , gingival scores and PTVs showed no significant differences between the two groups . A low level of positive correlation between plaque scores , gingival scores , probing depths and vertical bone loss was noted . CONCLUSION Immediately loaded two implants supporting a ball-retained m and ibular overdenture are associated with more marginal bone resorption and increased probing depths when compared with conventionally loaded implants after 3 years . The bone resorption and probing depths at distal and labial sites are significantly higher than those at mesial and lingual sites . Clinical outcomes do not differ significantly between loading protocol This prospect i ve study has been design ed to compare the results of immediate and delayed loading of implant-retained m and ibular overdentures after a 2-year follow-up . Twenty patients have been r and omly divided into two groups . Group 1 patients ( test group ) received four ITI implants in the intraforaminal area of the m and ible . Octa abutments were immediately screwed on implants ; 2 days after surgery , the implants were rigidly connected with a U-shaped Dolder gold bar and loaded with an overdenture . Group 2 patients ( control group ) received , in the same area , the same type and number of implants , which were left to heal according to the st and ard protocol . At 3 - 4 months , Octa abutments were screwed on the implants and the same prosthetic procedure of the test group was applied . The minimum follow-up period lasted 2 years , with recall appointments at 2 weeks , 1 , 3 , 6 months , 1 year and every following year postoperatively , evaluating : MPI , MBI , PD , Periotest and radiographic peri-implant bone resorption . Success criteria according to Albrektsson et al. were used . Only one implant out of the 40 of group 2 failed , whereas none failed in group 1 . No statistical difference of the clinical parameters evaluated was noticed in the two groups . Therefore , immediate loading of implants , if connected with a U-shaped bar , can provide the same results of the ' traditional ' technique as far as osseointegration and short-term survival rates of implants are concerned . Moreover , this method significantly shortens the treatment period , thus increasing patient satisfaction PURPOSE To report the clinical and radiographic outcomes of a 3-year follow-up of immediately and early loaded two-implant-supported m and ibular overdentures . MATERIAL S AND METHODS Forty edentulous patients were r and omly subdivided into two groups . In the immediate loading group , two Straumann implants were splinted with a Dolder bar and loaded with a m and ibular overdenture within the first 48 hours postoperative . In the early loading group , the two implants were loaded with an overdenture 6 weeks postoperative . St and ardized intraoral radiographs using a film holder were obtained at 1 month and 3 years . Two independent observers assessed marginal bone loss twice , independently , and analysis of variance ( ANOVA ) was used to follow up marginal bone level changes . RESULTS In total , there were 26 remaining patients available at the 3-year followup ( 15 immediate and 11 early ) . One implant was lost in the early loading group , and no implants were lost in the immediate loading group . All superstructures and dentures were adequately functional at the 3-year control . Mean radiographic marginal bone loss between baseline and the 3-year follow-up was 0.35 ± 0.63 mm for immediately loaded implants and 0.31 ± 0.96 mm for early loaded implants . The difference between the two groups was not statistically significant ( P = .26 ) . CONCLUSION Within the limitations of this trial and the short follow-up period and high dropout rate , the immediate loading protocol was found to be comparable in its clinical and radiographic outcomes to the early loading protocol for the two-implant Dolder bar-supported m and ibular overdentures |
13,822 | 25,456,641 | Internet blood glucose monitoring systems ( IBGMS ) are associated with improved glycemic control in patients with type 2 diabetes ( T2D ) who are pharmacologically managed , using oral agents or insulin .
IBGMS improves glycemic levels in patients with type 1 diabetes ( T1D ) .
IBGMS has not led to increased hypoglycemia .
Mechanisms underlying IBGMS-associated glycemic improvement extend beyond optimizing insulin dose titration .
The most important effects seem to be associated with increased patient self-motivation and improved patient-physician communication .
IBGMS have been recommended in clinical practice guidelines , and their effectiveness and safety in trials suggest that this approach is appropriate for patients with T1D or T2D | null | null |
13,823 | 23,979,968 | Conclusion None of the studies are sufficiently free from method ological bias to recommend any of the treatments investigated .
Of those examined , ESWT appears to have the most promise | Background Medial tibial stress syndrome ( MTSS ) is a common exercise-induced leg injury among athletes and military personnel .
Several treatment options have been described in the literature , but it remains unclear which treatment is most effective .
Objective The objective of this systematic review was to assess the effectiveness of any intervention in the treatment of MTSS . | 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 Background The only three r and omized trials on the treatment of MTSS were all performed in military population s. The treatment options investigated in this study were not previously examined in athletes . This study investigated if functional outcome of three common treatment options for medial tibial stress syndrome ( MTSS ) in athletes in a non-military setting was the same . Methods The study design was r and omized and multi-centered . Physical therapists and sports physicians referred athletes with MTSS to the hospital for inclusion . 81 athletes were assessed for eligibility of which 74 athletes were included and r and omized to three treatment groups . Group one performed a grade d running program , group two performed a grade d running program with additional stretching and strengthening exercises for the calves , while group three performed a grade d running program with an additional sports compression stocking . The primary outcome measure was : time to complete a running program ( able to run 18 minutes with high intensity ) and secondary outcome was : general satisfaction with treatment . Results 74 Athletes were r and omized and included of which 14 did not complete the study due a lack of progress ( 18.9 % ) . The data was analyzed on an intention-to-treat basis . Time to complete a running program and general satisfaction with the treatment were not significantly different between the three treatment groups . Conclusion This was the first r and omized trial on the treatment of MTSS in athletes in a non-military setting . No differences were found between the groups for the time to complete a running program . Trial registration CCMO ; The effect of low-energy laser therapy on shin splints was examined in a r and omized study with an unblinded design . Constripts from the Jutl and Dragoon regiment with shin splints were given either active laser treatment ( 40 mW in 60 sec per cm tender tibia edge ) or placebo laser . All patients were exempted from normal duty concerning activities like running and march . Forty-nine patients participated in the study , 23 in the laser group and 26 in the control group . From the start the study was design ed to be double-blind , but by accident the code was broken towards the end of the study . We found no significant differences between the groups regarding pain visual analog score and readiness to return to active duty after 14 days Objective The purpose of this study was to describe the results of two treatment regimens for medial tibial stress syndrome ( MTSS ) ; a grade d running programme and the same running programme with additional shockwave therapy ( extracorporeal shockwave therapy ; ESWT ) . Design A prospect i ve observational controlled trial . Setting Two different sports medicine departments . Participants 42 athletes with MTSS were included . Intervention Patients from one hospital were treated with a grade d running programme , while patients from the other hospital were treated with the same grade d running programme and focused ESWT ( five sessions in 9 weeks ) . Main Outcome Measures Time to full recovery ( the endpoint was being able to run 18 min consecutively without pain at a fixed intensity ) . Results The time to full recovery was significantly faster in the ESWT group compared with the patients who only performed a grade d running programme , respectively 59.7±25.8 and 91.6±43.0 days ( p=0.008 ) . Conclusions This prospect i ve observational study showed that MTSS patients may benefit from ESWT in addition to a grade d running programme . ESWT as an additional treatment warrants further investigation in a prospect i ve controlled trial with the addition of r and omisation and double blinding Objective To study the additional effect of a pneumatic leg brace with st and ard rehabilitation for the treatment of medial tibial stress syndrome ( MTSS ) in recruits . Methods In a single blinded r and omized study , 15 recruits ( age 17 - 22 ) followed a rehabilitation programme consisting of leg exercises and a grade d running programme . Recruits performed daily exercises and ran three times a week . The running programme consisted of 6 consecutive phases . One group was , after r and omization , additionally provided with a pneumatic leg brace . Follow-up was provided every other week . Days to completing the running programme was the primary outcome measure , the Sports Activity Rating Scale ( SARS ) score and satisfaction with the treatment were secondary outcome measures . Results In total 14 recruits completed the rehabilitation programme . No differences were found in the number of days until phase six of the running schedule was finished between the brace and the control group ( Brace 58.8 ± 27.7 ( mean ± SD ) vs Non-Brace 57.9 ± 26.2 ( mean ± SD , p = 0.57 ) . Also no differences were found in the SARS scores between the groups . Overall satisfaction with the treatment was 6.4 ± 1.1 ( mean ± SD ) on a 1 - 10 scale for the brace group and 7.1 ± 0.7 ( mean ± SD ) for the control group ( p = 0.06 ) . Comfort of the brace was assessed as 4.8 ± 1.3 ( mean ± SD ) on a 1 - 10 scale . Conclusions No additional large effect of the pneumatic leg brace could be found in recruits and wearing of the brace was not feasible , since the wearing comfort was low OBJECTIVE The purpose of this study was twofold : to determine whether asymptomatic distance runners exhibit cortical tibial abnormalities on CT and to determine the diagnostic accuracy of CT in athletes with medial tibial stress syndrome . MATERIAL S AND METHODS A cross-sectional study with high-resolution CT of both tibiae was performed on 41 subjects : 20 asymptomatic distance runners , 11 distance runners with unilateral or bilateral pain due to medial tibial stress syndrome ( 14 painful tibiae ) , and 10 volunteers not involved in a sport . The group was composed of 13 women and 28 men , ranging in age from 18 to 26 years . A total of 82 tibiae , 14 painful and 68 painless , were evaluated . On the basis of CT findings , tibiae were classified in three groups , and correlation between CT classification and symptoms was made . RESULTS Among distance runners , the presence of CT abnormalities was found in 14 ( 100 % ) of 14 painful tibiae in patients with medial tibial stress syndrome and in 8 ( 16.6 % ) of 48 painless tibiae . The difference was statistically significant ( p < 0.001 , Fisher 's exact test ) . Sensitivity , specificity , positive predictive value , negative predictive value , and accuracy of CT in diagnosing medial tibial stress syndrome were 100 % , 88.2 % , 63.6 % , 100 % , and 90.2 % , respectively . CONCLUSION High-resolution CT has high diagnostic accuracy in depicting medial tibial stress syndrome . Cortical abnormalities can also be seen in some asymptomatic distance runners Purpose To identify the incidence of medial tibial stress syndrome ( MTSS ) in a group of naval recruits undergoing a 10-week basic training period and to determine potential risk factors . Method One hundred and twenty-four recruits ( 84 men and 40 women ) were followed prospect ively during basic training . Anthropometric and lower limb biomechanical data were recorded at the start of the program along with injury history and previous sporting activity for the 3 months prior to enlisting . Recruits were monitored during training for development of medial tibial strees syndrome and were asked to complete an exit interview at the end of the program . Results Forty recruits ( 22 men and 18 women ) developed medial tibial stress syndrome , giving an incidence of 35 % . A significant relationship existed between gender and medial tibial stress syndrome ( P= .012 ) , with female recruits more likely to develop medial tibial stress syndrome than male recruits ( 53 % vs 28 % ) . A risk estimate revealed a relative risk of 2.03 . The biomechanical results indicated a more pronated foot type ( P= .002 ) in the medial tibial stress syndrome group when compared to the control group . A risk estimate established that recruits with a more pronated foot type had a relative risk of 1.70 . Conclusion Identifying a pronated foot type prior to training may help reduce the incidence of medial tibial stress syndrome by early intervention to control abnormal pronation . Findings of a higher incidence of medial tibial stress syndrome among female recruits require further investigation Diagnosis and management strategies for shin splints in active duty military population s closely resemble those in civilian athletic population s. There is a paucity of evidence supporting the use of many of these interventions . The purpose of this study was to present data on the Shin Saver orthosis as a treatment for shin splints in an active duty military population and to review current condition management . Twenty-five subjects diagnosed with shin splints by a U.S. Army physical therapist were r and omly assigned to a shin orthosis treatment group or a control group . There was no significant difference between treatment and control groups in days to finish a 0.5-mile run pain free . Visual analog scales for pain at intake versus after 1 week of relative rest revealed no significant improvement in symptoms in either group . Current best- practice guidelines support a treatment program of rest , cryotherapy , and a graduated walk-to-run program Background Although the exact cause of medial tibial stress syndrome is unclear , changes in bone metabolism are likely to be involved . Hypothesis Localized low bone mineral density at the junction of the middle and distal thirds of the tibia in patients with medial tibial stress syndrome develops in conjunction with the symptoms ; these changes are reversible and are not inherited . Study Design Prospect i ve cohort study . Methods Bone mineral density in 14 adult male athletes with long-st and ing medial tibial stress syndrome was measured when they were symptomatic and after recovery ( mean follow-up , 5.7 years ) . Repeat measurements were also made prospect ively in 13 nonathlete control subjects and single measurements were made in 18 healthy athletes . Results Bone mineral density was 9 % ± 11 % higher in the proximal tibia but 11 % ± 12 % lower in the tibial region corresponding to pain in patients when compared with nonathlete control subjects . It increased by 19 % ± 11 % in the region of pain after recovery from symptoms and , at follow-up , was no lower than in nonathlete control subjects . Conclusion Athletes with medial tibial stress syndrome and increased scintigraphic uptake regain normal tibial bone mineral density after recovery from symptoms . Initially localized low bone mineral density is not an inherited condition , but instead may develop in conjunction with the symptoms |
13,824 | 17,107,291 | Our findings revealed that most studies measured screening ( or intention ) and knowledge ; fewer measured recommended IDM-related constructs and none measured all outcomes proposed for evaluating IDM interventions . | Interventions to promote informed decision making ( IDM ) for cancer screening are increasingly common .
The result ing body of literature provides an opportunity for a systematic review of measures in use . | Purpose . To conduct a pilot test of a decision aid design ed to help patients choose among currently recommended colorectal cancer screening programs . Methods . R and omized controlled trial comparing a patient decision aid based on multi criteria decision-making theory with a simple educational intervention . Patient population . 96 patients at average risk for colorectal cancer seen in an Internal Medicine practice in Rochester , New York . Outcome measures . The two primary outcome measures were patient decision process and the decision outcome . Patient decision process was assessed using the decisional conflict scale . Decision outcome was defined as the proportion of colorectal cancer screening plans carried out . Results . After controlling for the effects of the physicians in a factorial analysis of variance , patients who used the decision aid had lower decisional conflict regarding colorectal cancer screening decisions ( F ratio6.47 , P = 0.01 ) due to increased knowledge , better clarity of values , and higher ratings of the quality of the decisions they made . There was no difference between the groups in decision outcomes : 52 % of patients in the control group and 49 % in the experimental group completed planned screening tests ( P = 1.0 ) . Conclusions . In a pilot study , a multi criteria -based patient decision aid for colorectal cancer screening improved patients ’ decision-making processes but had no effect on the implementation of screening plans Developing an evidence base for making public health decisions will require using data from evaluation studies with r and omized and nonr and omized design s. Assessing individual studies and using studies in quantitative research syntheses require transparent reporting of the study , with sufficient detail and clarity to readily see differences and similarities among studies in the same area . The Consoli date d St and ards of Reporting Trials ( CONSORT ) statement provides guidelines for transparent reporting of r and omized clinical trials . We present the initial version of the Transparent Reporting of Evaluations with Nonr and omized Design s ( TREND ) statement . These guidelines emphasize the reporting of theories used and descriptions of intervention and comparison conditions , research design , and methods of adjusting for possible biases in evaluation studies that use nonr and omized design BACKGROUND The availability of several effective screening options for colorectal cancer ( CRC ) screening calls for involving patients in decision making about CRC screening . The current study examined ( 1 ) participant characteristics associated with their preferences for participation in CRC screening decision making , ( 2 ) correspondence between participant preferences for decision making and their usual participation in decision making , and ( 3 ) associations between participant decision-making preferences and CRC screening practice s and attitudes . METHODS Data were obtained using a r and om , population -based telephone survey , conducted during August 2001 and April 2002 , of 2119 community-living adults aged 50 to 75 years ( 56 % female ) residing in Long Isl and , NY . RESULTS Overall , 77 % reported that preferences for CRC screening decision making matched how screening decisions were usually made ( simple kappa coefficient=0.67 [ 0.64 - 0.69 ] ) . Fifteen percent preferred to make screening decisions themselves , while 25 % preferred to make decisions after considering their physician 's opinion ; nearly 50 % preferred to share decision making , and 16 % preferred that their physician make all screening decisions . Less education was associated with preferring that the physician make all screening decisions . Preferring physician involvement in screening decision making was associated with greater odds of citing no physician recommendation as a barrier to CRC screening , when compared to those who preferred no physician involvement . Preferring no physician involvement in decision making was associated with lower odds of reporting a recent CRC screening exam , as well as lower odds of endorsing positive attitudes and greater odds of endorsing negative attitudes toward CRC screening , when compared to participants who preferred physician involvement in decision making . Their attitudes also reflected intentions not to screen for CRC if they were asymptomatic , as well as the perception that they were not at personal risk for CRC . CONCLUSIONS Several factors were identified as significantly associated with preferences for decision making and deserve further exploration for their application to clinical practice The purpose of this study was to determine if providing men with information about screening for prostate cancer would enable them to assume a more active role in decision making with their family physician , and lower levels of anxiety and decisional conflict . Men were recruited from one family medical clinic in Winnipeg , Manitoba . One hundred men scheduled for a periodic health examination ( PHE ) were r and omly assigned to receive verbal and written information either prior to the PHE , or following the second interview . Men completed measures of preferred decisional role and anxiety prior to the PHE ; and assumed decisional role , decisional conflict , and anxiety post PHE . Results demonstrated that men who received the information prior to the PHE assumed a significantly more active role in making a screening decision , and had lower levels of decisional conflict post PHE . The two groups did not differ with regard to levels of state anxiety . Providing men with information enables them to make informed screening decisions with their family physicians BACKGROUND We tested an intervention based on social learning theory ( SLT ) to improve colorectal cancer ( CRC ) screening among Native Hawaiians , a group with low CRC screening rates . METHOD Sixteen Hawaiian civic clubs agreed to r and omization . Eight control clubs received a culturally targeted presentation , a free Fecal Occult Blood Test ( FOBT ) , and a reminder call . Eight experimental clubs also received culturally targeted education and free testing ; but , in line with SLT , education was delivered by a Native Hawaiian physician and Native Hawaiian CRC survivor , and members received an FOBT demo , were challenged to involve a family member in screening , and were telephoned multiple times to address change-related emotions and barriers . RESULTS One hundred twenty-one members age 50 and older from 16 clubs participated . At the club level , screening rates were modestly increased in four experimental clubs and six control clubs . Surprisingly , 64 % of participants reported being up to date with CRC screening at baseline . Only 13 individuals ( five in experimental arm and eight in the control arm ) were screened for the first time through this intervention , increasing the percent screened from 59 % to 67 % in the experimental group and from 69 % to 85 % in the control group . Although individuals in the experimental arm were more likely to rate the intervention as culturally appropriate , both arms realized similar and significant gains in CRC knowledge , attitudes , intent , and self-efficacy . CONCLUSIONS For Native Hawaiian individuals belonging to a network of civic clubs , an intervention based on SLT delivered by a Native Hawaiian physician and CRC survivor was less effective at further increasing compliance than was a culturally targeted educational session delivered by a non-Hawaiian nurse . That CRC screening compliance was high prior to our intervention suggests that we targeted a very health conscious segment of the Native Hawaiian population . Future work should focus on underserved segments of this indigenous group Patient satisfaction measures have previously addressed satisfaction with medical care , satisfaction with providers , and satisfaction with outcomes , but not satisfaction with the health care decision itself . As patients become more involved in health care decisions , it is important to underst and specific dynamics of the decision itself The Satisfaction with Decision ( SWD ) scale measures satisfaction with health care decisions . It was developed in the context of postmenopausal hormone-replacement therapy decisions The six-item scale has excellent reliability ( Cronbach 's alpha = 0.86 ) . Discriminant validity , tested by performing principal- components analysis of items pooled from the SWD scale and two conceptually related measures , was good . Correlation of the SWD scale with measures of satisfaction with other aspects of the decision-making process showed the SWD scale was correlated most highly ( 0.64 ) with " decisional confidence , " and least with " desire to participate in health care de cisions " and " satisfaction with provider " The SWD scale predicts decision certainty in this study . Use in an independent study showed that the SWD scale was correlated with the likelihood of patients ' intentions to get a flu shot . Further investigation in relation to other health decisions will establish the utility of the SWD scale as an outcome measure Key words : patient satisfaction ; medical decision making ; decision support ( Med Decis Making 1996;16:58 - 64 BACKGROUND Studies have shown that a majority of women with a family history of breast cancer have exaggerated perceptions of their own risk of this disease and experience excessive anxiety . In response to the need to communicate more accurate risk information to these women , specialized programs for breast cancer risk counseling have been initiated in medical centers across the United States . PURPOSE Our purpose was 1 ) to evaluate the impact of a st and ardized protocol for individualized breast cancer risk counseling on comprehension of personal risk among first-degree relatives of index breast cancer patients and 2 ) to identify women most and least likely to benefit from such counseling . METHODS This study is a prospect i ve r and omized trial comparing individualized breast cancer risk counseling to general health counseling ( control ) . We studied 200 women aged 35 years and older who had a family history of breast cancer in a first-degree relative . Women with a personal history of cancer were excluded . Risk comprehension was assessed as the concordance between perceived " subjective " lifetime breast cancer risk and estimated " objective " lifetime risk . RESULTS The results of logistic regression analysis showed that women who received risk counseling were significantly more likely to improve their risk comprehension , compared with women in the control condition ( odds ratio [ OR ] = 3.5 ; 95 % confidence interval [ CI ] = 1.3 - 9.5 ; P = .01 ) . However , in both groups , about two thirds of women continued to overestimate their lifetime risks substantially following counseling . Examination of subjects by treatment interaction effects indicated that risk counseling did not produce improved comprehension among the large proportion of women who had high levels of anxious preoccupation with breast cancer at base line ( P = .02 ) . In addition , white women were less likely to benefit than African-American women ( OR = 0.34 ; 95 % CI = 0.11 - 0.99 ; P = .05 ) . CONCLUSION Efforts to counsel women about their breast cancer risks are not likely to be effective unless their breast cancer anxieties are also addressed . IMPLICATION S Attention to the psychological aspects of breast cancer risk will be critical in the development of risk-counseling programs that incorporate testing for the recently cloned breast cancer susceptibility gene , BRCA1 ( and BRCA2 when that gene has also been cloned ) OBJECTIVE To describe women 's breast screening knowledge , attitudes , intentions and practice s. DESIGN Telephone survey . PARTICIPANTS R and om population -based sample of 383 women aged 50 to 69 , living in Ottawa-Carleton , and having no history of breast cancer . Participation rates were 81 % . RESULTS Only 47 % reported having had a mammogram within the two years before the survey , and 57 % had received a physical breast exam within the previous year . Intentions to arrange screening were positively correlated to income , previous mammography , encouragement to have a mammogram , knowledge , knowing a person with breast cancer , an absence of negative attitudes ( i.e. , mammograms unnecessary ) , and low decisional conflict . CONCLUSIONS Improvements in participation rates will be achieved only if women are convinced of the need for screening , and physicians encourage them to be screened BACKGROUND Little is known about what information affects men 's decisions about prostate cancer screening . METHODS We developed a four-part decision aid about prostate cancer screening and tested it in men , ages 45 - 85 , to determine how the information in each part--(1 ) the epidemiology of prostate cancer ; ( 2 ) the PSA test ; ( 3 ) prostate biopsy and treatment options for prostate cancer ; and ( 4 ) balance sheets to aid decision-making -- affected men 's interest in screening . RESULTS One hundred eighty-eight men from one general internal medicine clinic participated in our study ( response rate 65 % ) . Before the decision aid , 76 % were interested in screening ; 8 % were not ; and 16 % were undecided . The decision aid increased the proportion of men who knew the advantages ( + 28 % ; 95 % CI : 21 - 35 ) and disadvantages ( + 55 % ; 95 % CI : 48 - 63 % ) of screening . It also increased the proportion who knew enough to make a decision ( + 24 ; 95 % CI : 16 - 32 % ) . It did not change men 's interest in screening ( P = 0.134 ) . Twenty percent of men , however , did change their interest category . Men who were undecided at baseline were more likely to change than those who were interested or not interested . There were no clinical ly meaningful changes in interest following each component part of the decision aid . CONCLUSION Interest in prostate cancer screening is high and remained high after a 10 min decision aid . The decision aid increased the proportion of men with sufficient information to decide about screening . It also changed 20 % of men 's interest in screening . Because no single piece of information was influential to decision-making in all men , clinicians may want to tailor information to men 's individual needs OBJECTIVES Efforts to educate men about the controversy surrounding prostate cancer screening are well intended but rarely evaluated rigorously . We evaluated an evidence -based ( EB ) booklet for men design ed to promote informed decision-making . We also determined whether men 's preference for involvement in decision-making ( " passive " , " collaborative " or " active " ) modified its impact . SETTING AND METHODS Men aged 40 - 70 years were recruited from the practice s of 13 local general practitioners ( GPs ) in Sydney , Australia . They completed a self-administered question naire before seeing their GP , who , according to pre-r and omised codes , distributed either our EB booklet or conventional information . Post-test question naires were mailed to men three days later . Of the 248 eligible men recruited , 214 ( 86 % response rate ) returned post-test question naires . Knowledge of evidence and of risk of developing and dying from prostate cancer , attitudes , interest in screening for prostate-specific antigen ( PSA ) , worry and decisional conflict were the main outcome measures . RESULTS Compared with those receiving conventional information , men receiving the EB booklet had significantly improved knowledge ( 50 % of items correct , 95 % CI 46 - 53 % ; vs 45 % correct , 95 % CI 42 - 48 % ) ( p = 0.048 ) and lower levels of decisional conflict ( mean 21.6 , 95 % CI 20.7 - 22.5 ; vs mean 24.3 , 95 % CI 23.4 - 25.2 ) ( p < 0.001 ) . Interest in PSA screening was significantly reduced in both groups at post-test ( p < 0.001 ) . Men preferring a " passive " approach to decision-making gained as much from our EB booklet as those with " active " or " collaborative " preferences . CONCLUSIONS Our findings show the benefits of providing evidence -based information to men about PSA screening . Our EB booklet facilitated informed choice , even among " passive " decision-makers OBJECTIVE : To assess the impact of informed consent on elderly patients ’ colorectal cancer ( CRC ) screening preferences . DESIGN : R and omized , controlled trial . SETTING : Four general internal medicine practice s. PATIENTS : We studied 399 elderly patients visiting their primary care provider for routine office visits . INTERVENTIONS : Patients were r and omized to receive either a scripted control message briefly describing CRC screening methods or one of two informational interventions simulating an informed consent presentation about CRC screening . One intervention described CRC mortality risk reduction in relative terms ; the other , in absolute terms . MEASUREMENTS AND MAIN RESULTS : The main outcome measure was intent to begin or continue fecal occult blood testing ( FOBT ) , flexible sigmoidoscopy , or both . There was no difference in screening interest between the control group and the two information groups ( p=.8 ) . The majority ( 63 % ) of patients intended to begin or continue CRC screening . Informed patients were able to gauge more accurately the positive predictive value of screening ( p=.0009 ) . Control patients rated the efficacy of screening higher than did patients receiving relative risk reduction information , who rated it higher than did patients receiving absolute risk reduction information ( p=.0002 ) . CONCLUSIONS : Elderly patients appeared to underst and CRC screening information and use it to gauge the efficacy of screening , but provision of information had no impact on their preferences for screening . In view of the large proportion who preferred not to be screened , we conclude that elderly patients should be involved in the screening decision . However , factors other than provision of information must determine their CRC screening preferences OBJECTIVE We explored the influence of different but factual scenarios about prostate-specific antigen ( PSA ) screening on men 's interest in having PSA screening to detect early prostate cancer . DESIGN Cross-sectional , representative community survey . SETTING AND PARTICIPANTS A total of 514 men ( 89 % response fraction ) aged 50 - 70 years r and omly selected from a telephone directory data base in Sydney , Australia . MAIN VARIABLES STUDIED Demographic , health and psychological variables . MAIN OUTCOME VARIABLES Interest in undergoing screening in response to five unspecified scenarios and , elsewhere in our interview , a specified scenario in which PSA screening was mentioned explicitly . RESULTS When presented with a scenario describing a lack of evidence underpinning the efficacy of screening for an unspecified cancer , 61.2 % of men reported that they ' probably ' or ' definitely ' wanted to undergo screening for an unspecified cancer . Similar proportions reported that they ' probably ' or ' definitely ' wanted to undergo screening even at the risk of unmasking indolent cancer ( 60.9 % ) or without expert consensus about the value of screening ( 62.8 % ) . Greatest interest in screening was elicited in that scenario describing life-time risk of dying from prostate cancer ( 72.6 % ) ( P < 0.001 ) . Significantly fewer indicated they would ' probably ' or ' definitely ' want to undergo screening for a cancer for which there was uncertainty about treatment efficacy and known side-effects ( 46.1 % ) ( P < 0.001 ) . Increasing age was a consistent predictor of positive interest in screening . When asked later in our survey specifically about PSA screening , 68.1%'probably ' or definitely ' wanted PSA screening . CONCLUSION Public health policy makers need to ensure that men are provided with the scope of medical evidence germane to prostate cancer screening and treatment , thereby potentially improving prostate cancer screening decisions PURPOSE The efficacy of prostate cancer screening is uncertain , and professional organizations recommend educating patients about potential harms and benefits . We evaluated the effect of a videotape decision aid on promoting informed decision making about prostate cancer screening among primary care patients . METHODS A group of 160 men , 45 to 70 years of age , with no history of prostate cancer , were r and omized to view or not to view a 20-minute educational videotape before a routine office visit at a university-based family medicine clinic . The subjects were contacted again 1 year after their visit to assess their receipt of prostate cancer screening ( digital rectal examination [ DRE ] or prostate-specific antigen [ PSA ] testing ) , their satisfaction with their screening decision , and knowledge retention since the baseline assessment . RESULTS Follow-up assessment s were completed for 87.5 % of the intervention subjects and 83.8 % of the control subjects . The rate of DRE did not differ between the 2 groups . Prostate-specific antigen testing was reported by 24 of 70 ( 34.3 % ) intervention subjects and 37 of 67 ( 55.2 % ) control subjects ( P = .01 ) . African American men were more likely to have had PSA testing ( 9 of 16 , 56.3 % ) than were white men ( 13 of 46 , 28.3 % ) ( P = .044 ) . Satisfaction with the screening decision did not differ between the study groups . Intervention subjects were more knowledgeable of prostate cancer screening than were control subjects , although these differences declined within 1 year ( P < .001 ) . CONCLUSIONS Decision aids for prostate cancer screening can have a long-term effect on screening behavior and appear to promote informed decision making CONTEXT Although evidence -based guidelines recommend that physicians inform men about prostate cancer screening , the most efficient way to do this is not known . OBJECTIVE To evaluate whether a mailed educational pamphlet affected men 's knowledge about early detection of prostate cancer . DESIGN R and omized , controlled trial . SETTING Primary care clinic of the Minneapolis VA Medical Center . PATIENTS 342 men at least 50 years of age who responded to a mailed survey ( overall response rate , 68 % ) and did not report a history of prostate cancer . INTERVENTION " Early Prostate Cancer " pamphlet mailed to patients in the intervention group 1 week before their scheduled clinic appointments . OUTCOME MEASURES Patients ' responses to a survey mailed 1 week after their clinic appointments ; prostate-specific antigen ( PSA ) testing determined from electronic medical records . RESULTS Respondents were predominantly elderly white men ( mean age , 71 years ; 90 % white ) with chronic illnesses ( 48 % described their health as " fair " or " poor " ) . Men who received the educational pamphlet were better informed than men in the usual care group , as measured by correct responses to the following three questions about prostate cancer screening : the natural history of prostate cancer ( 32 % vs. 24 % ; P = 0.10 ) , whether treatment lengthens lives of men with early prostate cancer ( 56 % vs. 44 % ; P = 0.04 ) , and accuracy of PSA testing ( 46 % vs. 27 % ; P < 0.008 ) . The overall proportion of correctly answered questions was greater in the intervention group ( 45 % vs. 32 % ; P < 0.001 ) . Testing for PSA in the year after the index clinic appointments did not differ significantly between the intervention group and the usual care group ( 31 % vs. 37 % ; P > 0.2 ) . CONCLUSIONS Male veterans are poorly informed about the potential benefits and risks of prostate cancer screening . Although our mailed educational pamphlet enhanced knowledge only modestly , it was an inexpensive and easily implemented intervention BACKGROUND Use of the prostate-specific antigen ( PSA ) as a screening test remains highly controversial , particularly in older men . This study was undertaken to assess the impact of information on the preferences of older men for such screening . METHODS The elderly cohort ( age > or = 65 years ) of a larger r and omized trial was studied to determine the effect of a 3-minute scripted informational intervention on primary care patients ' interest in PSA screening and on potential predictors of screening interest . RESULTS Informed patients were significantly less interested in screening than were uninformed patients ( p = .006 ) . Informed patients considered PSA screening to be significantly less efficacious than did uninformed patients ( p = .004 ) , but among both uninformed and informed patients , perceived efficacy correlated with interest in screening ( multivariate OR 2.3 , 95 % CI 1.5 - 3.8 for uninformed patients ; OR 2.2 , 95 % CI 1.3 - 3.9 for informed patients ) . Perceived seriousness of prostate cancer predicted interest in screening among uninformed patients ( OR 1.8 , 95 % CI 1.3 - 2.6 ) , but not among informed patients . Informed patients who were married were less interested in screening than those who were single , divorced , or widowed ( OR 0.3 , 95 % CI .08 - 0.9 ) . Marital status did not predict screening interest among uninformed patients . CONCLUSIONS Involving elderly patients in the decision whether to screen with the PSA by providing them with information leads to a significant reduction in interest in such screening . Factors that appear to influence the screening preferences of informed elderly patients include perceived efficacy of screening and marital status , whereas uninformed patients are more likely to weigh the perceived seriousness of prostate cancer in their screening decision An experiment was design ed to account for intention-behavior discrepancies by applying the theory of planned behavior to contingent valuation . College students ( N = 160 ) voted in hypothetical and real payment referenda to contribute $ 8 to a scholarship fund . Overestimates of willingness to pay in the hypothetical referendum could not be attributed to moderately favorable latent dispositions . Instead , this hypothetical bias was explained by activation of more favorable beliefs and attitudes in the context of a hypothetical rather than a real referendum . A corrective entreaty was found to eliminate this bias by bringing beliefs , attitudes , and intentions in line with those in the real payment situation . As a result , the theory of planned behavior produced more accurate prediction of real payment when participants were exposed to the corrective entreaty R and omised evaluations of re sources to facilitate informed decisions about prostate cancer screening are rarely conducted . In this study , 421 men recruited from the community were r and omly allocated to receive a leaflet ( n = 140 ) or one of two re sources meeting criteria for a decision-aid : a video ( n = 141 ) or an evidence -based booklet , developed by the authors ( n = 140 ) . Men in all three groups demonstrated significant increases in knowledge scores from pre to post-test . Scores were significantly higher at post-test amongst those who had received our evidence -based booklet compared with men who received the leaflet or video ( P < 0.001 ) . Scores were significantly modified by men 's preferences for decisional control ( P = 0.002 ) . Decisional conflict was significantly lower amongst men receiving the evidence -based booklet ( P = 0.038 ) . Men receiving the evidence -based booklet also were less likely to accept a recommendation by a GP to undergo prostate-specific-antigen ( PSA ) screening ( P = 0.003 ) . Men require detailed information about the pros and cons of PSA screening in order to make an informed decision . Re sources are not equivalent in achieving these outcomes BACKGROUND Prostate cancer screening with serum prostate-specific antigen ( PSA ) and digital rectal examination ( DRE ) continues to increase . Our goal was to test the effect of a prostate cancer screening decision-aid on patients ' knowledge , beliefs , and use of prostate cancer screening tests . METHODS Our study was a r and omized controlled trial of a prostate cancer screening decision-aid consisting of an illustrated pamphlet as opposed to a comparison intervention . We included 257 men aged 50 to 80 years who were receiving primary care at a Department of Veterans Affairs Hospital in Milwaukee , Wisconsin . The decision-aid provided quantitative outcomes of prostate cancer screening with DRE and PSA . We subsequently evaluated prostate cancer screening knowledge , beliefs , and test use . RESULTS The illustrated pamphlet decision-aid was effective in improving knowledge of prostate cancer screening tests : 95 % of the experimental group were aware of the possibility of false-negative test results compared with 85 % of the comparison group ( P < .01 ) . Ninety-one percent of the experimental group were aware of the possibility of a false-positive screening test result compared with 65 % of the comparison group ( P < .01 ) . However , there was no difference in the use of prostate cancer screening between the experimental ( 82 % ) and comparison ( 84 % ) groups , ( P > .05 ) . CONCLUSIONS When used in a primary care setting , an illustrated pamphlet decision-aid was effective in increasing knowledge of prostate cancer screening tests but did not change the use of these tests OBJECTIVE To evaluate a patient-educational approach to shared decision making for prostate cancer screening . DESIGN R and omized controlled trial with preoffice visit assessment and 2-week follow-up . SETTING University-based family practice center . PATIENTS Men aged 45 through 70 years with no history of prostate cancer or treatment for prostate disease ( N = 160 ) . Two patients were unavailable for follow-up . INTERVENTION Twenty-minute educational videotape on advantages and disadvantages of prostate-specific antigen ( PSA ) screening for prostate cancer . MAIN OUTCOME MEASURES A measure of patients ' core knowledge of prostate cancer developed for this study , reported preferences for PSA testing , and ratings of the videotape . RESULTS Patients ' core knowledge at baseline was poor . At 2-week follow-up , subjects undergoing videotape intervention showed a 78 % improvement in the number of knowledge questions answered correctly ( P = .001 ) , and knowledge increased about mortality due to early-stage prostate cancer , PSA screening performance , treatment-related complications , and disadvantages of screening . No overall change was observed for control subjects . At follow-up , 48 ( 62 % ) of 78 intervention patients planned to have the PSA test compared with 64 ( 80 % ) of 80 control patients ( 18.5 % absolute reduction ; 95 % confidence interval , 4.6%-32.4 % ; P = .009 ) . Intervention subjects rated favorably the amount of information provided and the clarity , balance , and length of the videotape and would recommend the videotape to others . CONCLUSIONS Patient education regarding the potential benefits and harms of early detection of prostate cancer can lead to more informed decision making . Incorporating the PSA videotape into the periodic health examination for asymptomatic men aged 50 years and older is recommended The WATCH ( Wellness for African Americans Through Churches ) Project was a r and omized trial comparing the effectiveness of 2 strategies to promote colorectal cancer preventive behaviors among 587 African American members of 12 rural North Carolina churches . Using a 2 X 2 factorial research design , the authors compared a tailored print and video ( TPV ) intervention , consisting of 4 individually tailored newsletters and targeted videotapes , with a lay health advisor ( LHA ) intervention . Results showed that the TPV intervention significantly improved ( p < .05 ) fruit and vegetable consumption ( 0.6 servings ) and recreational physical activity ( 2.5 metabolic task equivalents per hour ) and , among those 50 and older ( n = 287 ) , achieved a 15 % increase in fecal occult blood testing screening ( p = .08 ) . The LHA intervention did not prove effective , possibly because of suboptimal reach and diffusion BACKGROUND We assessed the short-term impact of decision-making interventions on knowledge about mammography , accuracy of women 's breast cancer risk perceptions , attitudes toward mammography , satisfaction with decisions , and mammography use since the intervention . METHODS The study was conducted among women who were members of Blue Cross Blue Shield of North Carolina and were in their 40s or 50s at the time the study began in 1997 . Women were r and omly assigned to usual care ( UC ) , tailored print booklets ( TP ) alone , or TP plus telephone counseling ( TP+TC ) . RESULTS 12-month interviews were completed by 1127 women to assess short-term intervention effects . Generally , women who received TP+TC were significantly more knowledgeable about mammography and breast cancer risk and were more accurate in their breast cancer risk perceptions than women in the TP and UC groups . They also were more likely to have had a mammogram since the baseline interview . In multivariable analyses , we found significant benefits of the combination of TP+TC compared to TP and to UC for knowledge , accuracy of risk perceptions , and mammography use . DISCUSSION For complex decision-making tasks , such as women 's decisions about mammography in the face of controversy , the combination of TP and TC may be more effective than TP alone , and certainly more effective than UC . It is critical that investigators determine the topics for which TP is appropriate and the situations that require additional supportive interventions The purpose of this study was to refine an instrument to measure the Health Belief Model concepts of susceptibility , seriousness , benefits , barriers , health motivation , and confidence , using the context of breast cancer and breast self-examination . A Likert format was used for attitudinal scales . A r and om sample ( N = 581 ) of women 35 years and over was included . Items were subjected to content analysis by national experts . Construct validity was established using exploratory factor analysis . Predictive validity was established by relating breast self-examination behavior to breast self-examination attitudes , using simultaneous multiple regression and bivariate correlations . Cronbach alpha reliability coefficients for the revised scales ranged from .80 to .93 . Test-retest correlations ranged from .45 to .70 BACKGROUND Because of the many uncertainties surrounding screening for prostate cancer , authorities recommend that patients be involved in the screening decision . OBJECTIVE To determine the impact of informed consent on patient interest in undergoing prostate-specific antigen ( PSA ) screening . METHODS Men 50 years or older with no prior PSA testing and no history of prostate cancer presenting to 1 of 4 university-affiliated primary care practice s were eligible for enrollment . Patients were r and omized to receive either a scripted informational intervention simulating an informed consent presentation ( intervention group , n = 103 ) or a single sentence about the PSA ( control group , n = 102 ) . The main outcome measure was patient interest in undergoing PSA screening measured on a 5-point Likert scale . RESULTS Patients who received the informational intervention were significantly less interested in undergoing PSA screening than controls ( mean difference in interest , 0.8 on 5-point scale , P < .001 ) . Informed patients were much less likely to indicate high interest in screening ( odds ratio , 0.34 ; 95 % confidence interval , 0.19 - 0.60 ; P < .001 ) . In a multivariate model , family history of prostate cancer was associated with increased interest and advancing age with decreased interest in PSA screening , but the informational intervention remained the strongest predictor of interest . CONCLUSIONS Among primary care patients of predominantly lower socioeconomic status , those who received informed consent were significantly less interested in PSA screening than those who did not . For physicians who offer the PSA as a screening test , this finding highlights the importance of apprising patients of the associated benefits , burdens , and uncertainties and allowing them to participate in the screening decision OBJECTIVE : To assess the effect of providing structured information about the benefits and harms of mammography in differing frames on women ’s perceptions of screening . DESIGN : R and omized control trial . SETTING : General internal medicine academic practice . PARTICIPANTS : One hundred seventy-nine women aged 35 through 49.INTERVENTION : Women received 1 of 3 5-minute videos about the benefits and harms of screening mammography in women aged 40 to 49 . These videos differed only in the way the probabilities of potential outcomes were framed ( positive , neutral , or negative ) . MEASUREMENTS AND MAIN RESULTS : We measured the change in accurate responses to questions about potential benefits and harms of mammography , and the change in the proportion of participants who perceived that the benefits of mammography were more important than the harms . Before seeing the videos , women ’s knowledge about the benefits and harms of mammography was inaccurate ( 82 % responded incorrectly to all 3 knowledge questions ) . After seeing the videos , the proportion that answered correctly increased by 52 % , 43 % , and 30 % for the 3 knowledge questions , respectively , but there were no differences between video frames . At baseline , most women thought the benefits of mammography outweighed the harms ( 79 % positive frame , 80 % neutral frame , and 85 % negative frame ) . After the videos , these proportions were similar among the 3 groups ( 84 % , 81 % , 83 % , P=.93 ) . CONCLUSIONS : Women improved the accuracy of their responses to questions about the benefits and harms of mammography after seeing the videos , but this change was not affected by the framing of information . Women strongly perceived that the benefits of mammography outweighed the harms , and providing accurate information had no effect on these perceptions , regardless of how it was framed |
13,825 | 28,340,156 | Conclusion The lack of change in self-esteem suggests weight loss alone is insufficient to improve self-esteem .
Multicomponent weight management interventions require a specific focus on self-esteem to improve this outcome in overweight and obese adolescents | Objective Building self-esteem in overweight adolescents is key to long-term weight management ; yet , self-esteem is rarely a key outcome of adolescent weight management interventions .
This systematic review investigates the impact of multicomponent weight management interventions on self-esteem in overweight and obese adolescents . | BACKGROUND AND OBJECTIVE : Most clinic-based weight control treatments for youth have been design ed for preadolescent children by using family-based care . However , as adolescents become more autonomous and less motivated by parental influence , this strategy may be less appropriate . This study evaluated a primary care – based , multicomponent lifestyle intervention specifically tailored for overweight adolescent females . METHODS : Adolescent girls ( N = 208 ) 12 to 17 years of age ( mean ± SD : 14.1 ± 1.4 years ) , with a mean ± SD BMI percentile of 97.09 ± 2.27 , were assigned r and omly to the intervention or usual care control group . The gender and developmentally tailored intervention included a focus on adoptable healthy lifestyle behaviors and was reinforced by ongoing feedback from the teen ’s primary care physician . Of those r and omized , 195 ( 94 % ) completed the 6-month posttreatment assessment , and 173 ( 83 % ) completed the 12-month follow-up . The primary outcome was reduction in BMI z score . RESULTS : The decrease in BMI z score over time was significantly greater for intervention participants compared with usual care participants ( −0.15 in BMI z score among intervention participants compared with −0.08 among usual care participants ; P = .012 ) . The 2 groups did not differ in secondary metabolic or psychosocial outcomes . Compared with usual care , intervention participants reported less reduction in frequency of family meals and less fast-food intake . CONCLUSIONS : A 5-month , medium-intensity , primary care – based , multicomponent behavioral intervention was associated with significant and sustained decreases in BMI z scores among obese adolescent girls compared with those receiving usual care BACKGROUND Despite the high prevalence and negative physical and psychosocial consequences of overweight and obesity in adolescents , very little research has evaluated treatment in this population . Consequently , clinicians working with overweight and obese adolescents have little empirical research on which to base their practise . Cognitive behavioural therapy has demonstrated efficacy in promoting behaviour change in many treatment resistant disorders . Motivational interviewing has been used to increase motivation for change and improve treatment outcomes . In this paper we describe the rationale and design of a r and omised controlled trial testing the efficacy of motivational interviewing and cognitive behaviour therapy in the treatment of overweight and obese adolescents . METHODS Participants took part in a motivational interview or a st and ard semi-structured assessment interview and were then r and omly allocated to a cognitive behavioural intervention or a wait-list control condition . The cognitive behavioural intervention , the CHOOSE HEALTH Program , consisted of 13 individual treatment sessions ( 12 face-to-face , 1 phone call ) followed by 9 maintenance sessions ( 7 phone calls , 2 face-to-face ) . Assessment s were conducted prior to participation , after the treatment phase and after the maintenance phase of intervention . Improvement in body composition was the primary outcome ; secondary outcomes included improved cardiovascular fitness , eating and physical activity habits , family and psychosocial functioning . CONCLUSION Despite the demonstrated effectiveness of motivational interviewing and cognitive behavioural therapy in the long-term management of many treatment resistant disorders , these approaches have been under-utilised in adolescent overweight and obesity treatment . This study provides baseline data and a thorough review of the study design and treatment approach to allow for the assessment of the efficacy of motivational interviewing and cognitive behavioural therapy in the treatment of adolescent overweight and obesity . Data obtained in this study will also provide much needed information about the behavioural and psychosocial factors associated with adolescent overweight and obesity Background : The best outcomes for treating childhood obesity have come from comprehensive family-based programmes . However there are questions over their generalizability . Objective : To examine the acceptability and effectiveness of ‘ family-based behavioural treatment ’ ( FBBT ) for childhood obesity in an ethnically and socially diverse sample of families in a UK National Health Service ( NHS ) setting . Methods : In this parallel group , r and omized controlled trial , 72 obese children were r and omized to FBBT or a waiting-list control . Primary outcomes were body mass index ( BMI ) and BMI s.d . scores ( SDSs ) . Secondary outcomes were weight , weight SDSs , height , height SDSs , waist , waist SDSs , FM index , FFM index , blood pressure ( BP ) and psychosocial measures . The outcomes were assessed at baseline and after treatment , with analyses of 6-month data performed on an intent-to-treat ( ITT ) basis . Follow-up anthropometric data were collected at 12 months for the treatment group . Results : ITT analyses included all children with baseline data ( n=60 ) . There were significant BMI SDS changes ( P<0.01 ) for the treatment and control groups of −0.11 ( 0.16 ) and −0.10 ( 1.6 ) . The treatment group showed a significant reduction in systolic BP ( −0.24 ( 0.7 ) , P<0.05 ) and improvements in quality of life and eating attitudes ( P<0.05 ) , with no significant changes for the control group . However the between-group treatment effects for BMI , body composition , BP and psychosocial outcomes were not significant . There was no overall change in BMI or BMI SDSs from 0–12 months for the treatment group . No adverse effects were reported . Conclusions : Both treatment and control groups experienced significant reductions in the level of overweight , but with no significant difference between them . There were no significant group differences for any of the secondary outcomes . This trial was registered at http://www.controlled-trials.com/ under IS RCT N 51382628 Abstract Background The Loozit ® Study is a r and omised controlled trial investigating extended support in a 24 month community-based weight management program for overweight to moderately obese , but otherwise healthy , 13 to 16 year olds . Methods This pre-post study examines the two month outcomes of the initial Loozit ® group intervention received by both study arms . Adolescents ( n = 151 ; 48 % male ) and their parents separately attended seven weekly group sessions focused on lifestyle modification . At baseline and two months , adolescents ' anthropometry , blood pressure , and fasted blood sample were assessed . Primary outcomes were two month changes in body mass index ( BMI ) z-score and waist-to-height-ratio ( WHtR ) . Secondary outcomes included changes in metabolic profile , self-reported dietary intake/patterns , physical and sedentary activities , psychological characteristics and social status . Changes in outcome measures were assessed using paired sample s t-tests for continuous variables or McNemar 's test for dichotomous categorical variables . Results Of the 151 adolescents who enrolled , 130 ( 86 % ) completed the two month program . Among these 130 adolescents ( 47 % male ) , there was a statistically significant ( P < 0.01 ) reduction in mean [ 95 % CI ] BMI ( 0.27 kg/m2 [ 0.41 , 0.13 ] ) , BMI z-score ( 0.05 [ 0.06 , 0.03 ] ) , WHtR ( 0.02 [ 0.03 , 0.01 ] ) , total cholesterol ( 0.14 mmol/L [ 0.24 , 0.05 ] ) and low-density lipoprotein cholesterol ( 0.12 mmol/L [ 0.21 , 0.04 ] ) . There were improvements in all psychological measures , the majority of the dietary intake measures , and some physical activities ( P < 0.05 ) . Time spent watching TV and participating in non-screen sedentary activities decreased ( P < 0.05 ) . Conclusions The Loozit ® program may be a promising option for stabilizing overweight and improving various metabolic factors , psychological functioning and lifestyle behaviors in overweight adolescents in a community setting .Trial registration Australian New Zeal and Clinical Trials Registry OBJECTIVE We examined the effect of a 12-week family-based cognitive behavioural weight management programme developed for use in primary care setting s. METHODS The sample consisted of 49 children with obesity ( aged 7 - 13 years ; mean ± SD : 10.68 ± 1.24 ) . Families were r and omly assigned to immediate start-up of treatment or to a 12-week waiting list condition . Outcome measures were body mass index st and ard deviation score ( BMI SDS ) , self-esteem , symptoms of depression and blood parameters indicative of cardio-metabolic risk . Assessment s were conducted at baseline , post-treatment , post-waiting list and 12 months after treatment termination . RESULTS The mean reduction for the treatment group was -0.16 BMI SDS units compared with an increase of 0.04 units for the waiting list group ( p = .001 ) . For the entire sample , there was a significant post-treatment improvement on BMI SDS ( p = .001 ) , all self-esteem measures ( p = .001-.041 ) and symptoms of depression ( p = .004 ) . The mean BMI SDS reduction was -0.18 units post-treatment , and it was maintained at 12-month follow-up . Significant reductions were found in blood lipid levels of total cholesterol ( p = .03 ) , LDL-cholesterol ( p = .005 ) and HDL-cholesterol ( p = .01 ) at 12-month follow-up . The favourable effect on most of the psychological measures waned from post-treatment to follow-up , but not approaching baseline levels . Boys demonstrated significantly greater reductions in BMI SDS than girls ( p = .001 ) , while baseline psychiatric co-morbidity did not influence BMI SDS outcome . CONCLUSIONS The treatment shows significant and favourable effects on BMI SDS , self-esteem and symptoms of depression compared with a waiting list condition The aim of the study was to investigate prospect ively the direction of the relationship between adolescent girls ' body dissatisfaction and self-esteem . Participants were 242 female high school students who completed question naires at two points in time , separated by 2 years . The question naire contained measures of weight ( BMI ) , body dissatisfaction ( perceived overweight , figure dissatisfaction , weight satisfaction ) and self-esteem . Initial body dissatisfaction predicted self-esteem at Time 1 and Time 2 , and initial self-esteem predicted body dissatisfaction at Time 1 and Time 2 . However , linear panel analysis ( regression analyses controlling for Time 1 variables ) found that aspects of Time 1 weight and body dissatisfaction predicted change in self-esteem , but not vice versa . It was concluded that young girls with heavier actual weight and perceptions of being overweight were particularly vulnerable to developing low self-esteem AIM This study evaluates the efficacy of the Choose Health program , a family-based cognitive behavioural lifestyle program targeting improved eating and activity habits , in improving body composition , cardiovascular fitness , eating and activity behaviours in overweight and obese adolescents . METHOD The sample comprised 29 male and 34 female overweight ( n = 15 ) or obese ( n = 48 ) adolescents aged 11.5 - 18.9 years ( M = 14.3 , SD = 1.9 ) . Participants were r and omly allocated to treatment or waitlist control conditions ; waitlist condition participants were offered treatment after 6 months . DEXA-derived and anthropometric measures of body composition ; laboratory-based cycle ergometer and field-assessed cardiovascular fitness data ; objective and self-report physical activity measures ; and self-report measures of eating habits and 7-day weighed food diaries were used to assess treatment outcome . Adherence to treatment protocol s was high . RESULTS Treatment result ed in significant ( p < .05 ) and sustained improvements in a range of body composition ( body fat , percent body fat , lean mass ) and anthropometric measures ( weight , BMI , BMI -for-age z-score and percentiles ) . Minimal improvements were seen in cardiovascular fitness . Similar results were obtained in completer and intention-to-treat analysis . Poor adherence to assessment protocol s limits conclusions that can be drawn from physical activity and dietary data . CONCLUSIONS Participation in the Choose Health program result ed in significant improvement in body composition . Longer-term follow up is required to determine the durability of intervention effects . Alternative approaches to the measurement of diet and physical activity may be required for adolescents Objective : Since peers have such an important influence on adolescents , we evaluated the efficacy of adding peer-based ‘ adventure therapy ’ to a st and ard cognitive-behavioral weight control program for overweight adolescents . Methods : Adolescents ( N=76 ) aged 13–16 years and 20 to 80 % overweight ( M=60.56 % , s.d.=15.17 % ) , were r and omly assigned to one of two treatment conditions : cognitive-behavioral group treatment with ‘ adventure therapy ’ similar to Outward Bound ® ( cognitive-behavioral treatment with peer-enhanced adventure therapy ( CBT+PEAT ) ) or cognitive-behavioral group treatment with aerobic exercise ( CBT+EXER ) . Anthropometric and psychosocial measures were obtained at baseline , at the end of the 16-week intervention , and at 10 months following r and omization . Results : Adolescents assigned to both treatment conditions demonstrated significant weight loss over time , F=29.06 , df=2 , 53 , P<0.01 . Average weight loss did not differ significantly between groups ( −5.31 kg for CBT+PEAT and −3.20 kg for CBT+EXER ) at the end of treatment . There was a significant difference in the percentage of participants maintaining a minimum 4.5 kg ( 10 pounds ) weight loss ( 35 % in the CBT+PEAT condition vs 12 % in the CBT+EXER condition , P=0.042 ) 10 months from r and omization . We also observed a significant age by treatment group interaction , such that older adolescents r and omized to CBT+PEAT demonstrated more than four times the weight loss of older adolescents assigned to CBT+EXER ( M=−7.86 kg vs M=−1.72 kg ) at the end of treatment . Conclusions : Peer-based ‘ adventure therapy ’ is a promising adjunct to st and ard cognitive-behavioral weight control intervention for adolescents , and may be most effective for older adolescents Recent findings indicate that nearly 50 % of black American women are obese and that adolescence is a critical period for the development of their obesity . This study investigated the efficacy of a behavioral weight control program in 36 black female adolescents with a mean age of 14.0 years , weight of 95.0 kg , and height of 163.2 cm . All subjects participated in the same 16-week program but had different levels of parent participation : ( 1 ) child alone with no parent participation ; ( 2 ) mother and child treated in the same session ; and ( 3 ) mother and child treated in separate but concurrent session . At the end of the 16-week program , children in the three conditions lost 1.6 , 3.7 , and 3.1 kg , respectively . Differences among conditions were not statistically significant ; however , a secondary analysis revealed that the greater the number of sessions attended by mothers , the greater their daughters ' weight losses . Weight reduction was associated with significant improvements in body composition , serum total cholesterol concentrations , and psychological status . Results are discussed in terms of the need to improve the maintenance of weight loss in adolescents and to explore possible differences between black and white females in their preferred body types OBJECTIVE To evaluate the impact of a 12-month multicomponent school-based obesity prevention program , Nutrition and Enjoyable Activity for Teen Girls among adolescent girls . DESIGN Group r and omized controlled trial with 12-month follow-up . SETTING Twelve secondary schools in low-income communities in the Hunter and Central Coast regions of New South Wales , Australia . PARTICIPANTS Three hundred fifty-seven adolescent girls aged 12 to 14 years . INTERVENTION A multicomponent school-based intervention program tailored for adolescent girls . The intervention was based on social cognitive theory and included teacher professional development , enhanced school sport sessions , interactive seminars , nutrition workshops , lunch-time physical activity sessions , h and books and pedometers for self-monitoring , parent newsletters , and text messaging for social support . MAIN OUTCOME MEASURES Body mass index ( BMI , calculated as weight in kilograms divided by height in meters squared ) , BMI z score , body fat percentage , physical activity , screen time , dietary intake , and self-esteem . RESULTS After 12 months , changes in BMI ( adjusted mean difference , -0.19 ; 95 % CI , -0.70 to 0.33 ) , BMI z score ( mean , -0.08 ; 95 % CI , -0.20 to 0.04 ) , and body fat percentage ( mean , -1.09 ; 95 % CI , -2.88 to 0.70 ) were in favor of the intervention , but they were not statistically different from those in the control group . Changes in screen time were statistically significant ( mean , -30.67 min/d ; 95 % CI , -62.43 to -1.06 ) , but there were no group by time effects for physical activity , dietary behavior , or self-esteem . CONCLUSIONS A school-based intervention tailored for adolescent girls from schools located in low-income communities did not significantly reduce BMI gain . However , changes in body composition were of a magnitude similar to previous studies and may be associated with clinical ly important health outcomes . TRIAL REGISTRATION anzctr.org.au Identifier : 12610000330044 The aim of this study was to evaluate the effectiveness of the Mind , Exercise , Nutrition , Do it ( MEND ) Program , a multicomponent community-based childhood obesity intervention ( www.mend central .org ) . One hundred and sixteen obese children ( BMI > or= 98 th percentile , UK 1990 reference data ) were r and omly assigned to intervention or waiting list control ( 6-month delayed intervention ) . Parents and children attended eighteen 2-h group educational and physical activity sessions held twice weekly in sports centers and schools , followed by a 12-week free family swimming pass . Waist circumference , BMI , body composition , physical activity level , sedentary activities , cardiovascular fitness , and self-esteem were assessed at baseline and at 6 months . Children were followed up 12 months from baseline ( 0 and 6 months postintervention for the control and intervention group , respectively ) . Participants in the intervention group had a reduced waist circumference z-score ( -0.37 ; P < 0.0001 ) and BMI z-score ( -0.24 ; P < 0.0001 ) at 6 months when compared to the controls . Significant between-group differences were also observed in cardiovascular fitness , physical activity , sedentary behaviors , and self-esteem . Mean attendance for the MEND Program was 86 % . At 12 months , children in the intervention group had reduced their waist and BMI z-scores by 0.47 ( P < 0.0001 ) and 0.23 ( P < 0.0001 ) , respectively , and benefits in cardiovascular fitness , physical activity levels , and self-esteem were sustained . High-attendance rates suggest that families found this intensive community-based intervention acceptable . Further larger controlled trials are currently underway to confirm the promising findings of this initial trial OBJECTIVE . We conducted a proof-of-concept , r and omized , controlled trial to investigate the effects of a supervised exercise therapy intervention on psychopathologic outcomes in obese adolescents . METHODS . The participant sample consisted of 81 adolescents ( age : 11–16 years ) who had been referred to a children 's hospital for evaluation of obesity or who responded to a community advertisement . Participants were assigned r and omly to exercise therapy , an equal-contact exercise placebo intervention , or usual care . Intervention participants attended 3 one-on-one sessions per week for 8 weeks and then completed a home program for another 6 weeks . Outcomes included self-perceptions ( self-esteem ) , depression , affect , physical activity , aerobic fitness , and BMI . RESULTS . A total of 18 of 81 participants were categorized as morbidly obese ( BMI SD score : > 3.5 ; adult equivalent BMI : ≥40 ) . At baseline , 30.3 % of participants had a Children 's Depression Inventory score of ≥13 , and 27 % reported recent suicidal ideation . Repeated- measures mixed analysis of covariance ( controlling for baseline scores ) revealed significant changes in physical self-worth , associated measures of self-esteem , and physical activity over time , consistently favoring exercise therapy . There were no significant changes in BMI . CONCLUSIONS . Findings confirmed psychopathologic conditions as a serious health concern in obese and morbidly obese adolescents . Our study is the first r and omized , controlled trial to demonstrate that a brief supervised exercise therapy intervention has the potential to improve psychopathologic outcomes significantly and to increase physical activity in obese adolescents , relative to usual care OBJECTIVES To assess the outcomes of the Loozit adolescent weight management intervention and to evaluate the effect of additional therapeutic contact 12 months into the program . DESIGN A 24-month , 2-arm r and omized controlled trial . Results at 12 months are presented . SETTING Community health center and children 's hospital in Sydney , Australia . PARTICIPANTS A total of 151 overweight or obese 13- to 16-year-olds . INTERVENTION In the first 2 months ( phase 1 ) , participants received 7 adolescent and parent weekly sessions focused on lifestyle modification . From 2 to 24 months ( phase 2 ) , adolescents attended booster sessions once every 3 months . During phase 2 , adolescents r and omized to the additional therapeutic contact arm also received telephone coaching and electronic communications once every 2 weeks . OUTCOME MEASURES Baseline to 12-month changes in body mass index z score and waist to height ratio ( primary outcomes ) and changes in metabolic , psychosocial , and behavioral variables . RESULTS Of 151 r and omized adolescents , 82.1 % completed 12-month follow-up . Intent-to-treat analyses showed significant reductions in mean body mass index z score ( -0.09 ; 95 % CI , -0.12 to -0.06 ) , waist to height ratio ( -0.02 ; 95 % CI , -0.03 to -0.01 ) , total cholesterol level ( -4 mg/dL ; 95 % CI , -8 to 0 mg/dL ; to convert to millimoles per liter , multiply by 0.0259 ) , and triglycerides level ( geometric mean , -80 mg/dL ; 95 % CI , -88 to -71 mg/dL ; to convert to millimoles per liter , multiply by 0.0113 ) . Most psychosocial outcomes improved , including global self-worth , but there were few dietary , physical activity , or sedentary behavior changes . No difference was found in primary outcomes between participants who did or did not receive additional therapeutic contact . CONCLUSIONS The Loozit r and omized controlled trial produced a significant but modest reduction in body mass index z score and improved psychosocial outcomes at 12 months . Supplementary telephone and electronic contact provided no additional benefit at 12 months . Trial Registration anzctr.org.au Identifier : 12606000175572 AIM To report our experiences with recruiting overweight and obese 13- to 16-year-olds for the Loozit ® weight management r and omised control trial ( RCT ) and to identify effective strategies for recruiting adolescents from the community to a treatment trial . METHODS The Loozit RCT is a two-arm , community-based , lifestyle intervention that aims to evaluate the effect of additional therapeutic contact provided via telephone coaching and electronic communications as an adjunct to the Loozit group programme . Strategic areas that were targeted to recruit adolescents included media , schools , health professionals and community organisations . The programme aim ed to recruit a cohort of 12 - 16 adolescents ( body mass index z-score range 1.0 - 2.5 ) aged 13 - 16 years every 3 months over 3 years . Information regarding recruitment and eligibility to participate was initially assessed during a telephone screen . The relative cost effectiveness of recruitment strategies was determined based on recruitment rates and costs including administrative costs and research assistant time . RESULTS Out of 474 enquiries , 32 % result ed in an enrollment to the RCT . Newspaper articles and school newsletters accounted for nearly 60 % of enquiries and enrollments and were the most cost-effective recruitment strategies . Common reasons for in eligibility for inclusion in the RCT were adolescents being too young ( 21 % ) and parents consenting but adolescents refusing to participate ( 17 % ) . CONCLUSIONS The most successful recruitment strategies for the Loozit RCT were local newspapers and school newsletters . Future studies should consider involving a Public Relations department and other potentially cost-effective strategies such as peer recruitment This paper reports the final 24-month outcomes of a r and omized controlled trial evaluating the effect of additional therapeutic contact ( ATC ) as an adjunct to a community-based weight-management program for overweight and obese 13–16-year-olds . ATC involved telephone coaching or short-message-service and /or email communication once per fortnight . Adolescents were r and omized to receive the Loozit group program — a two-phase behavioral lifestyle intervention with ( n=73 ) , or without ( n=78 ) , ATC in Phase 2 . Adolescents/parents separately attended seven weekly group sessions ( Phase 1 ) , followed by quarterly adolescent sessions ( Phase 2 ) . Assessor-blinded , 24-month changes in anthropometry and metabolic health included primary outcomes body mass index ( BMI ) z-score and waist : height ratio ( WHtR ) . Secondary outcomes were self-reported psychosocial and lifestyle changes . By 24 months , 17 adolescents had formally withdrawn . Relative to the Loozit program alone , ATC largely had no impact on outcomes . Secondary pre-post assessment of the Loozit group program showed mean ( 95 % CI ) reductions in BMI z-score ( −0.13 ( −0.20 , −0.06 ) ) and WHtR ( −0.02 ( −0.03 , −0.01 ) ) in both arms , with several metabolic and psychosocial improvements . Adjunctive ATC did not provide further benefits to the Loozit group program . We recommend that further work is needed to optimize technological support for adolescents in weight-loss maintenance . Australian New Zeal and Clinical Trials Registry Number ACTRNO12606000175572 BACKGROUND Weight-related problems are prevalent in adolescent girls . PURPOSE To evaluate New Moves , a school-based program aim ed at preventing weight-related problems in adolescent girls . DESIGN School-based group-r and omized controlled design . SETTING / PARTICIPANTS 356 girls ( mean age=15.8±1.2 years ) from six intervention and six control high schools . More than 75 % of the girls were racial/ethnic minorities and 46 % were overweight or obese . Data were collected in 2007 - 2009 and analyzed in 2009 - 2010 . INTERVENTION An all-girls physical education class , supplemented with nutrition and self-empowerment components , individual sessions using motivational interviewing , lunch meetings , and parent outreach . MAIN OUTCOME MEASURES Percentage body fat , BMI , physical activity , sedentary activity , dietary intake , eating patterns , unhealthy weight control behaviors , and body/self-image . RESULTS New Moves did not lead to significant changes in the girls ' percentage body fat or BMI but improvements were seen for sedentary activity , eating patterns , unhealthy weight control behaviors , and body/self-image . For example , in comparison to control girls , at 9-month follow-up , intervention girls decreased their sedentary behaviors by approximately one 30-minute block a day ( p=0.050 ) ; girls increased their portion control behaviors ( p=0.014 ) ; the percentage of girls using unhealthy weight control behaviors decreased by 13.7 % ( p=0.021 ) ; and improvements were seen in body image ( p=0.045 ) and self-worth ( p=0.031 ) . Additionally , intervention girls reported more support by friends , teachers , and families for healthy eating and physical activity . CONCLUSIONS New Moves provides a model for addressing the broad spectrum of weight-related problems among adolescent girls . Further work is needed to enhance the effectiveness of interventions to improve weight status of youth |
13,826 | 28,960,400 | In conclusion , despite the limited number of studies , there is a clear association with outcome in the presence of IMVI . | Extramural venous invasion ( EMVI ) is a well-known prognostic factor in colorectal cancer ( CRC ) .
Vascular invasion within the bowel wall , intramural vascular invasion ( IMVI ) , has received less attention and its incidence and prognostic importance in CRC is not completely known . | Background and aims : There is a need for objective easily determined pathological prognostic parameters in Dukes ' B colon carcinoma to allow selection of such patients for further treatment as the role of adjuvant chemotherapy for these patients remains unclear . This study was initiated to assess the influence of pathological factors on prognosis in an unselected prospect i ve series of Dukes ' B colonic cancer . Methods : The Gloucester Colorectal Cancer study , established in 1988 , recruited more than 1000 cases . Meticulous pathological assessment of the 268 Dukes ' B colonic cancer resections in this series included evaluation of all pathological factors that could influence staging and prognosis . All patients entered a comprehensive follow up system . Results : Four pathologically determined factors — peritoneal involvement , venous spread ( both submucosal and extramural ) , spread to involve a surgical margin , and perforation through the tumour — were independent prognostic factors in multivariate analysis . Combining these four factors into a simple cumulative scoring system generated clinical ly useful prognostic groups . Conclusions : The cumulative prognostic index allows apportionment of patients with Dukes ' B colon cancer into defined prognostic groups , which in turn could allow more objective selection of patients for adjuvant therapy , especially as part of clinical trials Objective : To examine the clinical utility of improved detection of venous invasion ( VI ) in patients undergoing potentially curative resection of colorectal cancer . Background : VI is a feature of colorectal cancer ( CRC ) progression . Elastica staining can be used to improve detection of VI and correspondingly its prediction of patient survival . Methods : A single-center , observational study of pathology variables , including detection of VI by staining for elastica , using 631 stage I to III CRC specimens , collected from 1997 to 2009 ( 176 analyzed retrospectively and 455 analyzed prospect ively ) , was performed . Results : VI was detected in 56 % of patients with CRC . Over a median follow-up period of 73 months , 238 patients died ( 134 from cancer ) . On multivariate analysis , VI by elastica staining was associated with a shorter survival duration , independent of other pathology features , in all cases [ hazard ratio ( HR ) = 3.94 , 95 % confidence interval ( CI ) : 2.33–6.65 , P < 0.001 ] and in node-negative cases ( HR = 3.55 , 95 % CI : 1.81–6.97 ; P < 0.001 ) . In the absence of elastica-detected VI , with the exception of T stage , no other pathology features were associated with survival time . Therefore , the combination of T stage and VI ( TVI ) on survival was examined . Five-year cancer mortality could be stratified between 100 % and 54 % for patients with node-negative tumors and between 100 % and 33 % for patients with node-positive tumors . In all cases , the TVI had similar predictive value as that of T stage and node status ( TNM ) . In node-negative disease , TVI had superior predictive value . Conclusions : The results of the present study have prompted the development of a novel tumor staging system based on TVI . The TVI has clinical utility , especially in node-negative disease , in predicting outcome following curative resection for CRC Colorectal cancer is a common malignancy and a leading cause of cancer related death . Cancer staging following resection is key to determining any adjuvant therapy in those patients with high risk disease . In colorectal cancer , tumour stage and lymph node stage are the main pathological factors which have been considered to influence outcome . Increasing emphasis is now being placed on other factors , especially the presence of extramural venous invasion ( EMVI ) . It is important to underst and the relationship of EMVI with other pathological factors and to confirm that in an individual centre that EMVI is being detected at an appropriate rate and is of prognostic significance . This comprehensive study assesses the reporting and prognostic significance of EMVI in a single centre , using prospect ively collected data from histopathology reports of a cohort of 2405 patients who underwent surgery for colorectal cancer over a nine year period . Overall , EMVI was reported in 27.9 % of colorectal cancer excision specimens . In tumours ( n = 1928 ) that had not received neoadjuvant therapy , the presence of EMVI varied significantly depending on tumour site ( χ2 = 12.03 , p<0.005 ) , tumour stage ( χ2 = 268.188 , p<0.001 ) , lymph node stage ( χ2 = 294.368 , p<0.001 ) and Dukes ’ stage ( χ2 = 253.753 , p<0.001 ) . Multivariate analysis confirmed EMVI as a significant independent prognostic indicator ( p<0.001 ) . In conclusion , the presence of EMVI as an independent prognostic indicator is shown and is related to other pathological and prognostic factors . This study emphasises the requirement for the accurate identification of EMVI in colorectal cancer excision specimens and also underst and ing the relationship of EMVI with other prognostic factors BACKGROUND : Extramural venous invasion is a known independent predictor of poor prognosis after resection of colorectal adenocarcinoma , but the prognostic value of mural venous invasion alone and the association between venous invasion and prognosis within tumor stages has received little research attention . OBJECTIVE : This study aim ed to determine whether associations between mural and extramural venous invasion and outcome differ among tumor stages after adjustment for other factors known to influence prognosis . DESIGN : This study is a retrospective analysis of prospect ively collected data . SETTING S : Data were drawn from a registry of 3040 consecutive patients undergoing resection between 1980 and 2005 under the care of specialist surgeons in a tertiary referral public hospital and an affiliated private hospital . A st and ardized protocol was used for the pathological assessment of specimens . MAIN OUTCOME MEASURES : The primary outcomes measured were overall survival , cancer-specific survival , and recurrence . RESULTS : There was no significant association between venous invasion and survival in stages A ( n = 544 ) or B ( n = 1078 ) . In stage C ( n = 899 ) , overall survival time was significantly shorter in patients with mural invasion alone or extramural invasion ( both p < 0.001 ) than in those without invasion , and this persisted after adjustment for other prognostic variables . Equivalent bivariate associations were found in stage D , but only the effect of extramural invasion persisted after adjustment . LIMITATIONS : Our findings arise from the experience of a single surgical group and may not be generalizable to other setting s. Only hematoxylin and eosin staining was used . CONCLUSIONS : The association between venous invasion and prognosis was stage specific . Both mural venous invasion alone and extramural venous invasion independently predicted overall survival in patients with stage C tumors , but not in patients with stages A , B , or D tumors . Although mural invasion alone was rare , the separate reporting of both mural and extramural invasion in patients with stage C tumor is informative and desirable We performed a long-term prospect i ve study on venous invasion of colorectal cancer . The degree of venous invasion was divided into four stages ( V0 through V3 ) . Venous invasion was classified into three types by location ( Vx , Vy , and Vz ) . Hepatic metastasis occurred in 27 % , 33 % , and 20 % of patients with V2 , V3 , and Vz tumors , respectively . Local recurrence occurred in 33 % and 15 % of the V3 and Vz groups , respectively . However , there were no significant differences among the groups in terms of the rate of pulmonary metastasis . The 6-year survival rate for Dukes ' stage B tumors was 94 % , 88 % , and 74 % in the V0 , V1 , and V2 groups , respectively . There was a significant difference in the survival rate between patients with V0 tumors and V2 and V3 tumors . However , no significant difference was noted in the location . In Dukes ' stage C tumors , on the other h and , the survival rate was 77 % , 56 % , and 44 % in the V1 , V2 , and V3 groups , respectively . Also , it was 85 % , 73 % , and 45 % in Vx , Vy , and Vz cases , respectively . Significant differences were noted between V1 and V3 ( or V2 ) , and between Vz and Vx ( or Vy ) . It appears that the degree and location of venous invasion influence not only hepatic metastasis , local recurrence , and survival rates but also have prognostic value |
13,827 | 29,540,415 | AND IMPLICATION S OF KEY FINDINGS Our analysis indicates conclusively that the current approach to exercise-based CR has no effect on all-cause mortality or cardiovascular mortality , when compared with a no-exercise control .
There may be a small reduction in hospital admissions following exercise-based CR that is unlikely to be clinical ly important . | OBJECTIVES To determine the contemporary effectiveness of exercise-based cardiac rehabilitation ( CR ) in terms of all-cause mortality , cardiovascular mortality and hospital admissions . | Aim To determine the effectiveness and cost-effectiveness of a mobile phone intervention to improve exercise capacity and physical activity behaviour in people with ischaemic heart disease ( IHD ) . Methods and results In this single-blind , parallel , two-arm , r and omized controlled trial adults ( n = 171 ) with IHD were r and omized to receive a mobile phone delivered intervention ( HEART ; n = 85 ) plus usual care , or usual care alone ( n = 86 ) . Adult participants aged 18 years or more , with a diagnosis of IHD , were clinical ly stable as out patients , able to perform exercise , able to underst and and write English , and had access to the Internet . The HEART ( Heart Exercise And Remote Technologies ) intervention involved a personalized , automated package of text messages and a secure website with video messages aim ed at increasing exercise behaviour , delivered over 24 weeks . All participants were able to access usual community-based cardiac rehabilitation , which involves encouragement of physical activity and an offer to join a local cardiac support club . All outcomes were assessed at baseline and 24 weeks and included peak oxygen uptake ( PVO2 ; primary outcome ) , self-reported physical activity , health-related quality of life , self-efficacy and motivation ( secondary outcomes ) . Results showed no differences in PVO2 between the two groups ( difference −0.21 ml kg−1 min−1 , 95 % CI : −1.1 , 0.7 ; p = 0.65 ) at 24 weeks . However significant treatment effects were observed for selected secondary outcomes , including leisure time physical activity ( difference 110.2 min/week , 95 % CI : −0.8 , 221.3 ; p = 0.05 ) and walking ( difference 151.4 min/week , 95 % CI : 27.6 , 275.2 ; p = 0.02 ) . There were also significant improvements in self-efficacy to be active ( difference 6.2 % , 95 % CI : 0.2 , 12.2 ; p = 0.04 ) and the general health domain of the SF36 ( difference 2.1 , 95 % CI : 0.1 , 4.1 ; p = 0.03 ) at 24 weeks . The HEART programme was considered likely to be cost-effective for leisure time activity and walking . Conclusions A mobile phone intervention was not effective at increasing exercise capacity over and above usual care . The intervention was effective and probably cost-effective for increasing physical activity and may have the potential to augment existing cardiac rehabilitation services Background : The CardioFit internet-based expert system was design ed to promote physical activity in patients with coronary heart disease ( CHD ) who were not participating in cardiac rehabilitation . Design : This r and omized controlled trial compared CardioFit to usual care to assess its effects on physical activity following hospitalization for acute coronary syndromes . Methods : A total of 223 participants were recruited at the University of Ottawa Heart Institute or London Health Sciences Centre and r and omly assigned to either CardioFit ( n = 115 ) or usual care ( n = 108 ) . The CardioFit group received a personally tailored physical-activity plan upon discharge from the hospital and access to a secure website for activity planning and tracking . They completed five online tutorials over a 6-month period and were in email contact with an exercise specialist . Usual care consisted of physical activity guidance from an attending cardiologist . Physical activity was measured by pedometer and self-reported over a 7-day period , 6 and 12 months after r and omization . Results : The CardioFit internet-based physical activity expert system significantly increased objective ly measured ( p = 0.023 ) and self-reported physical activity ( p = 0.047 ) compared to usual care . Emotional ( p = 0.038 ) and physical ( p = 0.031 ) dimensions of heart disease health-related quality of life were also higher with CardioFit compared to usual care . Conclusions : Patients with CHD using an internet-based activity prescription with online coaching were more physically active at follow up than those receiving usual care . Use of the CardioFit program could extend the reach of rehabilitation and secondary -prevention services OBJECTIVE To evaluate the effectiveness of a home-based cardiac rehabilitation ( CR ) program on post-coronary arteries bypass graft patients . METHODS This is a r and omized study conducted in King Fahd Armed Forces Hospital , Jeddah , Kingdom of Saudi Arabia between June 2008 and January 2010 . Forty-nine participants were r and omized to either a control group ( st and ard hospital treatment , n=21 ) or an intervention group ( home-based CR , n=28 ) . Data were collected before hospital discharge ( baseline test ) and repeated 6 months after hospital discharge ( follow-up test ) . RESULTS There were no significant differences between the groups in the body mass index , hemodynamics , serum fasting lipid profile , and Quality of Life question naire ( QoL ) ( p>0.05 ) , with differences in physical function and Hospital Anxiety and Depression Scales ( HADS ) ( p<0.05 ) at the baseline test . At the follow-up test , the intervention group showed greater improvement in health-related QoL and risk factors compared to the control group , with significant differences in fasting blood glucose , triglycerides , high density lipoprotein cholesterol , physical function , and both QoL and HADS question naires ( p<0.05 ) . The intervention group also demonstrated significant improvements in QoL , HADS , body mass index , heart rate , high density lipoprotein cholesterol and physical function ( p<0.05 ) , while significant differences were observed in the control group in heart rate , QoL and physical function ( p<0.05 ) . CONCLUSION The home-based CR program improves health-related QoL and risk factor profiles for patients following coronary arteries bypass graft to greater extent than the st and ard hospital care Background : The results of research into the outcomes of physical rehabilitation and its relationship with post-myocardial ischaemia survival and readmissions are inconclusive . Our primary aim was to evaluate the efficacy of a supervised exercise training programme in terms of decreasing hospital cardiac readmission in patients with myocardial ischaemia . Methods : We conducted a r and omised controlled trial including patients with myocardial ischaemia . Eligible patients were assigned to a control group receiving st and ard care or to an intervention group that took part in a supervised exercise training programme . The follow-up period was 12 months after hospital discharge . Results : Of 478 patients assessed for eligibility , 86 were r and omised to the control group ( n = 44 ) or the intervention group ( n = 42 ) . Cardiac readmission rates were 14 % versus 5 % ( p = 0.268 ) in the control and intervention groups , respectively , and all-cause readmission rates were 23 % versus 15 % ( p = 0.34 ) . There were no deaths in either group . More control patients were treated in the emergency services ( 50 % vs. 24 % ; p = 0.015 ) . In terms of health-related quality of life , patients in the intervention group presented with significant increases in functional capacity and mobility . More intervention patients returned to work ( 77.3 % vs. 36.0 % ; p = 0.005 ) . Conclusions : The supervised physical exercise programme was effective at reducing the number of emergency room visits and at increasing the percentage of patients who returned to work . It also improved patients ’ exercise capacity and increased their health-related quality of life . Although the results were promising , the programme was not associated with a significant reduction in cardiac and all-cause readmission rates The Women ’s Lifestyle Heart Trial was a small ( N=28 ) r and omized controlled trial to evaluate the effects of a comprehensive lifestyle self-management program ( very low-fat vegetarian diet , stress-management training , exercise , group support , and smoking cessation ) on reduction of cardiovascular risk factors in postmenopausal women with coronary heart disease ( CHD ) . Women assigned to the treatment condition ( Prime Time ) participated in a week-long retreat followed by twice-weekly 4-hour meetings . Endpoints were program adherence ; changes in lipid profiles , body mass , blood pressure , hypolipidemic and antihypertensive medications ; and quality of life . Risk factor and psychosocial evaluations were conducted at baseline and at 4 , 12 , and 24 months . Repeated measures analyses of covariance revealed that the dietary , stress management , and physical activity changes made by intervention women were dramatic and lasting . There were significantly greater improvements in the Prime Time condition compared to the usual care control group on body mass , angina symptoms , and quality of life , and a tendency for a greater reduction in blood pressure-lowering medications . Similar patterns were seen in lipids , blood pressure , and lipid-lowering medications , but did not reach significance . These results demonstrate that postmenopausal CHD women can make lasting lifestyle changes , and that these changes may reduce the need for cardiac medications and improve CHD risk factors and quality of life Drug therapy for hypercholesterolaemia has remained controversial mainly because of insufficient clinical trial evidence for improved survival . The present trial was design ed to evaluate the effect of cholesterol lowering with simvastatin on mortality and morbidity in patients with coronary heart disease ( CHD ) . 4444 patients with angina pectoris or previous myocardial infa rct ion and serum cholesterol 5.5 - 8.0 mmol/L on a lipid-lowering diet were r and omised to double-blind treatment with simvastatin or placebo . Over the 5.4 years median follow-up period , simvastatin produced mean changes in total cholesterol , low-density-lipoprotein cholesterol , and high-density-lipoprotein cholesterol of -25 % , -35 % , and + 8 % , respectively , with few adverse effects . 256 patients ( 12 % ) in the placebo group died , compared with 182 ( 8 % ) in the simvastatin group . The relative risk of death in the simvastatin group was 0.70 ( 95 % CI 0.58 - 0.85 , p = 0.0003 ) . The 6-year probabilities of survival in the placebo and simvastatin groups were 87.6 % and 91.3 % , respectively . There were 189 coronary deaths in the placebo group and 111 in the simvastatin group ( relative risk 0.58 , 95 % CI 0.46 - 0.73 ) , while noncardiovascular causes accounted for 49 and 46 deaths , respectively . 622 patients ( 28 % ) in the placebo group and 431 ( 19 % ) in the simvastatin group had one or more major coronary events . The relative risk was 0.66 ( 95 % CI 0.59 - 0.75 , p < 0.00001 ) , and the respective probabilities of escaping such events were 70.5 % and 79.6 % . This risk was also significantly reduced in subgroups consisting of women and patients of both sexes aged 60 or more . Other benefits of treatment included a 37 % reduction ( p < 0.00001 ) in the risk of undergoing myocardial revascularisation procedures . This study shows that long-term treatment with simvastatin is safe and improves survival in CHD patients Background It is widely believed that cardiac rehabilitation following acute myocardial infa rct ion ( MI ) reduces mortality by approximately 20 % . This belief is based on systematic review s and meta-analyses of mostly small trials undertaken many years ago . Clinical management has been transformed in the past 30–40 years and the findings of historical trials may have little relevance now . Objectives The principal objective was to determine the effect of cardiac rehabilitation , as currently provided , on mortality , morbidity and health-related quality of life in patients following MI . The secondary objectives included seeking programmes that may be more effective and characteristics of patients who may benefit more . Design , setting , patients , outcome measures A multi-centre r and omised controlled trial in representative hospitals in Engl and and Wales compared 1813 patients referred to comprehensive cardiac rehabilitation programmes or discharged to ‘ usual care ’ ( without referral to rehabilitation ) . The primary outcome measure was all-cause mortality at 2 years . The secondary measures were morbidity , health service use , health-related quality of life , psychological general well-being and lifestyle cardiovascular risk factors at 1 year . Patient entry ran from 1997 to 2000 , follow-up of secondary outcomes to 2001 and of vital status to 2006 . A parallel study compared 331 patients in matched ‘ elective ’ rehabilitation and ‘ elective ’ usual care ( without rehabilitation ) hospitals . Results There were no significant differences between patients referred to rehabilitation and controls in mortality at 2 years ( RR 0.98 , 95 % CI 0.74 to 1.30 ) or after 7–9 years ( 0.99 , 95 % CI 0.85 to 1.15 ) , cardiac events , seven of eight domains of the health-related quality of life scale ( ‘ Short Form 36 ’ , SF36 ) or the psychological general well-being scale . Rehabilitation patients reported slightly less physical activity . No differences between groups were reported in perceived overall quality of cardiac aftercare . Data from the ‘ elective ’ hospitals comparison concurred with these findings . Conclusion In this trial , comprehensive rehabilitation following MI had no important effect on mortality , cardiac or psychological morbidity , risk factors , health-related quality of life or activity . This finding is consistent with systematic review s of all trials reported since 1983 . The value of cardiac rehabilitation as practised in the UK is open to question 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 OBJECTIVES The goal of this study was to determine the effects of exercise training ( ET ) on functional capacity and quality of life ( QOL ) in patients who received percutaneous transluminal coronary angioplasty ( PTCA ) or coronary stenting ( CS ) , the effects on the restenosis rate and the outcome . BACKGROUND It is unknown whether ET induces beneficial effects after coronary angioplasty . METHODS We studied 118 consecutive patients with coronary artery disease ( mean age 57+/-10 years ) who underwent PTCA or CS on one ( 69 % ) or two ( 31 % ) native epicardial coronary arteries . Patients were r and omized into two matched groups . Group T ( n = 59 ) was exercised three times a week for six months at 60 % of peak VO2 . Group C ( n = 59 ) was the control group . RESULTS Only trained patients had significant improvements in peak VO2 ( 26 % , p < 0.001 ) and quality of life ( 26.8 % , p = 0.001 vs. C ) . The angiographic restenosis rate was unaffected by ET ( T : 29 % ; C : 33 % , P = NS ) and was not significantly different after PTCA or CS . However , residual diameter stenosis was lower in trained patients ( -29.7 % , p = 0.045 ) . In patients with angiographic restenosis , thallium uptake improved only in group T ( 19 % ; p < 0.001 ) . During the follow-up ( 33+/-7 months ) trained patients had a significantly lower event rate than controls ( 11.9 vs. 32.2 % , RR : 0.71 , 95 % confidence interval [ CI ] : 0.60 to 0.91 , p = 0.008 ) and a lower rate of hospital readmission ( 18.6 vs. 46 % , RR : 0.69 , 95 % CI : 0.55 to 0.93 , p < 0.001 ) . CONCLUSIONS Moderate ET improves functional capacity and QOL after PTCA or CS . During the follow-up , trained patients had fewer events and a lower hospital readmission rate than controls , despite an unchanged restenosis rate AIMS To investigate the long-term benefits of a six-week comprehensive cardiac rehabilitation programme on physical activity , psychological well-being and quality of life in patients with coronary heart disease . BACKGROUND Cardiac rehabilitation ( CR ) in short term improves exercise capacity and quality of life in patients with cardiac disease . However , the long-term benefits of CR are inconclusive . DESIGN A prospect i ve CR programme with repeated measures follow-up over 12 months . METHODS A six-week outpatient cardiac rehabilitation programme was conducted including 147 patients with coronary heart disease . Patients completed the physical activity energy expenditure ( seven-day recall activity ) , MacNew Heart Disease Health-Related Quality of Life ( MacNew ) and Hospital Anxiety and Depression scale ( HADs ) at baseline , six weeks , six and 12 months . RESULTS One hundred and five ( 71 % ) patients ( 76 male ) mean age of 61.8 ( SD 9.7 ) completed the four-measurement points . Analysis of variance revealed that total energy expenditure ( F ( 2 , 231 ) = 131 , p < 0.001 ) , HADs ( F ( 2 , 237 ) = 19.3 , p < 0.001 ) , depression score ( F ( 2 , 235 ) = 21.06 , p < 0.001 ) , anxiety score ( F ( 2,237 ) = 17.02 , p < 0.001 ) and MacNew ( F ( 2 , 197 ) = 77.02 , p < 0.001 ) were all statistically significant over time . Bonferroni pairwise follow-up confirmed significant positive differences ( p < 0.05 ) between baseline values and all subsequent measures over time . Depression was independently explained in 22 % of the variance in quality of life at 6 or 12 months . The energy expenditure was significantly higher for men compared to women ( F ( 1 , 103 ) = 31 , p < 0.001 ) . CONCLUSION A six-week cardiac rehabilitation programme is beneficial in improving quality of life , physical activity status , anxiety and depression . These benefits were maintained at 12 months . Elevated levels of depression were associated with impaired quality of life . RELEVANCE TO CLINICAL PRACTICE All relevant health care staff should be aware of the benefits of CR and routinely refer and encourage patients with cardiac disease to attend a cardiac rehabilitation programme . Depression and anxiety intervention strategies should be incorporated in cardiac rehabilitation programmes Background —Regular exercise in patients with stable coronary artery disease has been shown to improve myocardial perfusion and to retard disease progression . We therefore conducted a r and omized study to compare the effects of exercise training versus st and ard percutaneous coronary intervention ( PCI ) with stenting on clinical symptoms , angina-free exercise capacity , myocardial perfusion , cost-effectiveness , and frequency of a combined clinical end point ( death of cardiac cause , stroke , CABG , angioplasty , acute myocardial infa rct ion , and worsening angina with objective evidence result ing in hospitalization ) . Methods and Results —A total of 101 male patients aged ≤70 years were recruited after routine coronary angiography and r and omized to 12 months of exercise training ( 20 minutes of bicycle ergometry per day ) or to PCI . Cost efficiency was calculated as the average expense ( in US dollars ) needed to improve the Canadian Cardiovascular Society class by 1 class . Exercise training was associated with a higher event-free survival ( 88 % versus 70 % in the PCI group , P = 0.023 ) and increased maximal oxygen uptake ( + 16 % , from 22.7±0.7 to 26.2±0.8 mL O2/kg , P < 0.001 versus baseline , P < 0.001 versus PCI group after 12 months ) . To gain 1 Canadian Cardiovascular Society class , $ 6956 was spent in the PCI group versus $ 3429 in the training group ( P < 0.001 ) . Conclusions —Compared with PCI , a 12-month program of regular physical exercise in selected patients with stable coronary artery disease result ed in superior event-free survival and exercise capacity at lower costs , notably owing to reduced rehospitalizations and repeat revascularizations This prospect i ve study evaluated the effect of an individualized , comprehensive , home-based cardiac rehabilitation program combining exercise training with risk factor modification and psychosocial counseling on risk factors , psychological well-being , functional capacity , and work resumption in 99 post-percutaneous coronary interventions ( PCI ) patients r and omized to control ( st and ard care plus telephone follow-up , n=49 ) or intervention ( individualized , comprehensive , home-based cardiac rehabilitation , n=50 ) groups . Data were collected at time 1 ( T(1 ) ) during hospital admission , time 2 ( T(2 ) ) approximately 2 months post-PCI , and time 3 ( T(3 ) ) approximately 12 months post-PCI . Results suggest that the allocation to an individualized , comprehensive , home-based cardiac rehabilitation program provided more advantageous outcomes . At both follow-ups , the intervention group showed within-group improvement in serum cholesterol levels ( P<0.02 ; P<0.01 ) and exercise participation ( P<0.001 ; P<0.001 ) with differences in exercise participation favoring the intervention group ( P<0.01 ) at T(2 ) . Repeated measures ANOVA showed significant improvements over time in body mass index ( BMI ) ( P<0.01 ) , psychological well-being ( P<0.001 ) , and functional capacity ( P<0.001 ) for both groups . More patients in the intervention group had returned to work at T(2 ) ( P<0.001 ) and did so more quickly ( P<0.01 ) . These findings suggest that an individualized , comprehensive , home-based cardiac rehabilitation program improves risk factor profiles and work resumption patterns for patients following PCI AIM To investigate efficacy of early and long term physical training ( PT ) of moderate intensity in conditions of practical health care in Russia in patients with ischemic heart disease ( IHD ) of able to work age - survivors of acute coronary events . MATERIAL AND METHODS Three hundred ninety two patients were enrolled in this study . They were r and omized into intervention group " O " ( n=197 ) and control group " C " ( n=195 ) . Inclusion period was 3- 8 weeks from onset of myocardial infa rct ion ( MI ) , unstable angina ( UA ) , or intervention on coronary arteries . Patients were followed up for 1 year and efficacy of intervention was assessed by results of laboratory ( levels of lipids ) , instrumental ( ECG , exercise test on veloergometer , echocardiography ) , and clinical examination . In the group " O " regimen of PT with work loads of moderate intensity ( 50 - 60 % of power achieved during exercise test ) was used . Duration of FT was 45 - 60 min , frequency - 3 times a week . All patients received st and ard therapy for IHD and a lipid lowering drug when indicated . RESULTS Proofs of efficacy of PT in the given contingent of patients were obtained . This was manifested by significant increase of physical working capacity : prolongation of exercise time ( + 31.7 % , p<0.001 ) , increases of volume of work performed ( + 74.3 % , p<0.001 ) and efficiency of cardiac work according to results of exercise tests . All parameters were significantly different from those in the group " C " . Structural functional parameters of the heart also improved in the group " O " : left ventricular ( LV ) stroke volume increased 4.5 % ( p<0.005 ) , ejection fraction increased 7.2 % ( p<0.001 ) , diastolic LV volume decreased 2.5 % ( p<0.05 ) , systolic LV volume decreased 8.1 % ( p<0.001 ) . In the group " C " stroke volume and LV ejection fraction rose to a lesser degree - by 5.5 % ( p<0.01 ) and 2.9 % ( p<0.05 ) , respectively . Differences between groups in dynamics of these parameters turned out to be significant ( p<0.05 ) . Moreover in group " C " LV diastolic volume increased 2.3 % ( p<0.05 ) and systolic volume did not change , while left atrium increased 3.4 % ( p<0.002 ) . At intergroup comparison differences in dynamics of these parameters were significant ( p<0.005 ) . Analysis of lipid profile after 1 year showed no changes in patients of group " C " , while in group " O " it revealed significant ( 3.6 % ) lowering of total ( T ) cholesterol ( CH ) ( p<0.05 compared with baseline and change in group " C " ) and elevation of high density lipoprotein ( HDL ) CH ( + 12.3 % , p<0.001 ; compared with group " C " p<0.005 ) . Atherogeneity index TCH/HDLCH decreased 8.5 % in the group " O " ( p<0.01 ) , and increased 12 % ( p<0.02 ) in the group " C " , difference between groups was statistically significant ( p<0.001 ) . In the group " O " body mass index decreased 2.8 % ( p<0.001 ) , and frequency of attacks of angina decreased 50.8 % ( p<0.001 ; compared with group " C " p<0.001 ) . Statistically significant differences were registered between the following parameters of composite end point and surrogate points : total number of cardiovascular events - 26 ( 14.8 % ) vs 47 ( 27 % ) , p<0.01 ; number of cardiovascular catastrophes - 5 ( 3 % ) vs 15 ( 8.7 % ) , p<0.05 ; number of days out of work because of exacerbation of IHD per 1 person/year - 2.4 vs 4.2 , p<0.05 in groups " O " and " C " , respectively . Thus in the group " O " positive effect of PT on the course and outcomes of the disease was registered compared with the group " C " . CONCLUSION The data obtained are indicative of sufficient efficacy of the used program of PT and feasibility of its application in practice of ambulatory rehabilitation of patients with IHD - survivors of acute coronary events . It also can be looked upon as a method of secondary prevention as results of the study showed its positive impact on risk factors and outcomes of the disease AIMS AND OBJECTIVES To evaluate the one-year prognosis of a lifestyle counselling intervention ( diet , smoking cessation and exercise ) among patients who had open heart surgery . BACKGROUND Cardiovascular disease is the leading cause of morbidity worldwide in both developing and developed countries . Lifestyle modification plays an important role for patients who are at a high risk of developing cardiovascular disease and for those with an established cardiovascular disease . DESIGN R and omised , nonblind and lifestyle counselling intervention study with a one-year follow-up . METHODS A r and omised , nonblind intervention study was performed on 500 patients who had open heart surgery . After hospital discharge , 250 patients ( intervention group ) were r and omly allocated lifestyle counselling according to the recent guidelines provided by the European Society of Cardiology ( European Journal Preventive Cardiology , 19 , 2012 , 585 ) . The remaining 250 patients ( control group ) received the regular instructions . Primary end-point was the development of a cardiovascular disease ( nonfatal event ) during the first year ; secondary end-points included fatal events , smoking abstinence , dietary habits and a physical activity evaluation . RESULTS According to the primary end-point , the odds of having a nonfatal cardiovascular disease event are 0·56-times ( 95%CI 0·28 , 0·96 , p = 0·03 ) lower for the intervention group compared to the control group . One-year after surgery , it was found that participants in the intervention group were 1·96-times ( 95%CI 1·31 , 2·93 , p < 0·001 ) more likely to achieve dietary recommendations , 3·32-times ( 95%CI 2·24 , 4·91 , p < 0·001 ) more likely to achieve physical activity recommendations and 1·34-times ( 95%CI 1·15 , 1·56 , p < 0·001 ) more likely to return to work . CONCLUSION Lifestyle counselling intervention following open heart surgery can improve health outcomes and reduce the risk of a new cardiac event . Health care services must recommend and organise well-structured cardiac rehabilitation programmes adjusted to the patient 's needs . RELEVANCE TO CLINICAL PRACTICE A well-structured cardiac rehabilitation programme adjusted to the patient 's profile is a safe and cost-effective way to improve patients ' outcome INTRODUCTION AND OBJECTIVES Very little information is available on the effect of cardiac rehabilitation programs on long-term survival . The primary aim of this study was to assess the effect of a structured cardiac rehabilitation program on mortality in patients who had suffered acute myocardial infa rct ion . The secondary endpoint was the effect on morbidity . PATIENTS AND METHOD The study included 180 low-risk male patients aged under 65 years . Patients were r and omly assigned to one of 2 groups : 90 entered into a comprehensive cardiac rehabilitation program , and 90 served as a control group . The mean follow-up period was 10 years . RESULTS All-cause mortality was significantly lower in the intervention group : the 10-year survival rate was 91.8 % in the intervention group compared with 81.7 % in the control group ( P=.04 ) . There was also a decrease in cardiovascular mortality , though it was not statistically significant : the 10-year survival rate was 91.8 % in the intervention group compared with 83.8 % in the control group ( P=.10 ) . The incidence of non-fatal complications was lower in the intervention group ( 35.2 % vs 63.2 % , P=.03 ) , as was the incidence of unstable angina ( 15.7 % vs 33.9 % , P = .02 ) and cardiac heart failure ( 3.0 % vs 14.4 % , P=.02 ) , and the need for coronary intervention ( 8.4 % vs 22.9 % , P=.02 ) . CONCLUSIONS The application of a comprehensive cardiac rehabilitation program significantly decreased long-term mortality and morbidity in low-risk patients after acute myocardial infa rct ion OBJECTIVE To estimate the incremental effects on cost and quality of life of cardiac rehabilitation after an acute coronary syndrome . DESIGN Open r and omised controlled trial with 1 year 's follow-up . Analysis was on an intention-to-treat basis . SETTING Two tertiary hospitals in Sydney . INTERVENTION 18 sessions of comprehensive exercise-based outpatient cardiac rehabilitation or conventional care as provided by the treating doctor . PARTICIPANTS 113 patients aged 41 - 75 years who were self-caring and literate in English . Patients with uncompensated heart failure , uncontrolled arrhythmias , severe and symptomatic aortic stenosis or physical impairment were excluded . MAIN OUTCOME MEASURES Costs ( hospitalisations , medication use , outpatient visits , investigations , and personal expenses ) ; and measures of quality of life . Incremental cost per quality -adjusted life year ( QALY ) saved at 1 year ( this estimate combines within- study utility effects with reported 1-year risk of survival and treatment effects of rehabilitation on mortality ) . Sensitivity analyses around a base case estimate included alternative assumptions of no treatment effect on survival , 3 years of treatment effect on survival and variations in utility . RESULTS The estimated incremental cost per QALY saved for rehabilitation relative to st and ard care was 42,535 US dollars when modelling included the reported treatment effect on survival . This increased to 70,580 US dollars per QALY saved if treatment effect on survival was not included . The results were sensitive to variations in utility and ranged from 19,685 US dollars per QALY saved to rehabilitation not being cost-effective . CONCLUSIONS The effects on quality of life tend to reinforce treatment advantages on survival for patients having postdischarge rehabilitation after an acute coronary syndrome . The estimated base case incremental cost per QALY saved is consistent with those historically accepted by decision making authorities such as the Pharmaceutical Benefits Advisory Committee Objective To compare home-based cardiac rehabilitation ( CR ) with usual care ( control group with no rehabilitation ) in elderly patients who declined participation in centre-based CR . Design R and omised clinical trial with 12 months follow-up and mortality data after 5.5 years ( mean follow-up 4½ years ) . Setting Rehabilitation unit , Department of Cardiology , Copenhagen , Denmark . Participants Elderly patients ≥65 years with coronary heart disease . Intervention A physiotherapist made home visits in order to develop an individualised exercise programme that could be performed at home and surrounding outdoor area . Risk factor intervention , medical adjustment , physical and psychological assessment s were offered at baseline and after 3 , 6 and 12 months . Main outcome measurements The primary outcome was 6 min walk test ( 6MWT ) . Secondary outcomes were blood pressure , body composition , cholesterol profile , cessation of smoking , health-related quality of life ( HRQoL ) , anxiety and depression . Results 40 patients participated . The study population was characterised by high age ( median age 77 years , range 65–92 years ) and high level of comorbidity . Patients receiving home-based CR had a significant increase in the primary outcome 6MWT of 33.5 m ( 95 % CI : 6.2 to 60.8 , p=0.02 ) at 3 months , whereas the usual care group did not significantly improve , but with no significant differences between the groups . At 12 months follow-up , there was a decline in 6MWT in both groups ; −55.2 m ( 95 % CI : 18.7 to 91.7 , p<0.01 ) in the home group and −52.1 m ( 95 % CI : −3.0 to 107.1 , p=0.06 ) in the usual care group . There were no significant differences in blood pressure , body composition , cholesterol profile , cessation of smoking or HRQoL after 3 , 6 and 12 months follow-up . Conclusions Participation in home-based CR improved exercise capacity among elderly patients with coronary heart disease , but there was no significant difference between the home intervention and the control group . In addition , no significant difference was found in the secondary outcomes . When intervention ceased , the initial increase in exercise capacity was rapidly lost Introduction Current international guidelines for cardiac rehabilitation ( CR ) advocate moderate-intensity exercise training ( MISS , moderate-intensity steady state ) . This recommendation pre date s significant advances in medical therapy for coronary heart disease ( CHD ) and may not be the most appropriate strategy for the ‘ modern ’ patient with CHD . High-intensity interval training ( HIIT ) appears to be a safe and effective alternative , result ing in greater improvements in peak oxygen uptake ( VO2 peak ) . To date , HIIT trials have predominantly been proof-of-concept studies in the laboratory setting and conducted outside the UK . The purpose of this multicentre r and omised controlled trial is to compare the effects of HIIT and MISS training in patients with CHD attending UK CR programmes . Methods and analysis This pragmatic study will r and omly allocate 510 patients with CHD to 8 weeks of twice weekly HIIT or MISS training at 3 centres in the UK . HIIT will consist of 10 high-intensity ( 85–90 % peak power output ( PPO ) ) and 10 low-intensity ( 20–25 % PPO ) intervals , each lasting 1 min . MISS training will follow usual care recommendations , adhering to currently accepted UK guidelines ( ie , > 20 min continuous exercise at 40–70 % heart rate reserve ) . Outcome measures will be assessed at baseline , 8 weeks and 12 months . The primary outcome for the trial will be change in VO2 peak as determined by maximal cardiopulmonary exercise testing . Secondary measures will assess physiological , psychosocial and economic outcomes . Ethics and dissemination The study protocol V.1.0 , date d 1 February 2016 , was approved by the NHS Health Research Authority , East Midl and s — Leicester South Research Ethics Committee ( 16/EM/0079 ) . Recruitment will start in August 2016 and will be completed in June 2018 . Results will be published in peer- review ed journals , presented at national and international scientific meetings and are expected to inform future national guidelines for exercise training in UK CR . Trial registration number NCT02784873 ; pre- results BACKGROUND High-intensity interval training has been shown to be superior to moderate continuous exercise training in improving exercise capacity and endothelial function in patients with coronary artery disease . The objective of this study was to evaluate this training model on in-stent restenosis following percutaneous coronary intervention for stable or unstable angina . METHODS AND RESULTS We prospect ively r and omized 40 patients after percutaneous coronary intervention with implantation of a bare metal stent ( n = 30 ) or drug eluting stent ( n = 32 ) to a 6-month supervised high-intensity interval exercise training program ( n = 20 ) or to a control group ( n = 20 ) . At six months , restenosis , measured as in-segment late luminal loss of the stented coronary area , was smaller in the training group 0.10 ( 0.52 ) mm compared to the control group 0.39 ( 0.38 ) mm ( P = .01 ) . Reduction of late luminal loss in the training group was consistent with both stent types . Peak oxygen uptake increased in the training and control group by 16.8 % and 7.8 % , respectively ( P < .01 ) . Flow-mediated dilation improved 5.2 % ( 7.6 ) in the training group and decreased -0.1 % ( 8.1 ) in the control group ( P = .01 ) . Levels of high-sensitivity C-reactive protein decreased by -0.4 ( 1.1 ) mg/L in the training group and increased by 0.1 ( 1.2 ) mg/L in the control group ( P = .03 for trend ) . CONCLUSIONS Regular high-intensity interval exercise training was associated with a significant reduction in late luminal loss in the stented coronary segment . This effect was associated with increased aerobic capacity , improved endothelium function , and attenuated inflammation OBJECTIVE To evaluate the long-term effect of a cardiac rehabilitation and prevention program ( CRPP ) on quality of life ( QOL ) and its cost effectiveness . DESIGN Prospect i ve , r and omized controlled trial . SETTING University-affiliated outpatient cardiac rehabilitation and prevention center . PARTICIPANTS A total of 269 patients ( 76 % men ; mean age , 64+/-11 y ) with recent acute myocardial infa rct ion ( AMI ; n=193 ) or after elective percutaneous coronary intervention ( PCI ; n=76 ) were r and omized in a ratio of 2 to 1 . INTERVENTION Patients received either CRPP ( an 8-wk exercise and education class in phase 2 ) or conventional therapy without exercise program ( control group ) . They were followed until they had completed all 4 phases of the program ( ie , 2 y ) . MAIN OUTCOME MEASURES QOL assessment s , by using the Medical Outcomes Study 36-Item Short-Form Health Survey ( SF-36 ) and Symptoms Question naire , were performed at the end of each phase . Direct health care cost was calculated , whereas cost utility was estimated as money spent ( in US dollars ) per quality -adjusted life-year ( QALY ) gained . RESULTS In the CRPP group , 6 of the 8 SF-36 dimensions improved significantly by phase 2 and were maintained throughout the study period . Patients were less anxious and depressed , and felt more relaxed and contented . In the control group , none of the SF-36 dimensions were improved by phase 2 , and bodily pain was increased . In phase 4 , only 4 dimensions were improved . Symptoms were unchanged except for increased hostility score . There was a significant gain in net time trade-off in the CRPP group after phase 2 . The direct health care expenses in the CRPP and control groups were 15,292 dollars and 15,707 dollars per patient , respectively . Therefore , the cost utility calculated was 640 dollars saved per QALY gained . Savings attributable to CRPP were primarily explained by the lower rate ( 13 % vs 26 % of patients , chi2 test=3.9 , P < .05 ) and cost of subsequent PCI ( P = .01 ) . CONCLUSIONS In an era of managing patients with coronary heart disease , a short-course CRPP was highly cost effective in providing better QOL to patients with recent AMI or after elective PCI . In addition , the improvement of QOL was quick and sustained for at least 2 years after CRPP BACKGROUND Current guidelines broadly recommend comprehensive cardiac rehabilitation ( CCR ) , although evidence for this is still limited . We investigated the 12-month effect of hospital-based CCR versus usual care ( UC ) for a broadly defined group of cardiac patients within the modern therapeutic era of cardiology . METHODS We conducted a central ly r and omized single-center clinical trial with blinded assessment of the primary outcome : registry-based composite of total mortality , myocardial infa rct ion , or acute first-time readmission due to heart disease . Other outcomes were hospitalization , risk profile , and quality of life . The trial included 770 participants ( 20 - 94 years ) with congestive heart failure ( 12 % ) , ischemic heart disease ( 58 % ) , or high risk of ischemic heart disease ( 30 % ) . Comprehensive cardiac rehabilitation is composed of 6 weeks of intensive intervention and systematic follow-up for 10.5 months . RESULTS We r and omized 380 patients to CCR versus 390 to UC . R and omization was well balanced . The primary outcome occurred in 31 % of both groups ( relative risk 0.96 , 95 % confidence interval 0.78 - 1.26 ) . Compared with the UC group , CCR significantly reduced length of stay by 15 % ( 95 % confidence interval 1.1%-27.1 % , P = .04 ) , mean number of cardiac risk factors above target ( 4.5 vs 4.1 , P = .01 ) , patients with systolic blood pressure below target ( P = .003 ) , physically inactivity ( P = .01 ) , and unhealthy dietary habits ( P = .0003 ) . Short-Form-36 and Hospital Anxiety and Depression Scale did not differ significantly . CONCLUSION At 12 months , the CCR and UC groups did not differ regarding the primary composite outcome . Comprehensive cardiac rehabilitation significantly reduced length of hospital stay and improved cardiac risk factors BACKGROUND Limited data are available regarding the effects of phase III cardiac rehabilitation on the physical status and risk factors in elderly patients with coronary artery disease ( CAD ) . METHODS AND RESULTS Thirty-four male CAD patients ( > 65 years old ) were r and omly assigned to an intervention group ( n=18 ) or a control group ( n=16 ) . The intervention group participated in a phase III cardiac rehabilitation program consisting of exercise training , diet therapy , and weekly counseling for 6 months . In the control group , usual outpatient care was provided . In the intervention group , body mass index , waist size and fat weight significantly decreased ; peak VO2 and anaerobic threshold VO2 were maintained ; isokinetic peak torques of knee extensor and flexor muscles significantly increased ; anterior trunk flexibility was significantly improved . In the control group , all parameters were unchanged except for peak VO2 , which significantly decreased . In the intervention group , serum total cholesterol levels significantly decreased after cardiac rehabilitation . However , high-density lipoprotein-cholesterol and apoA-I levels also decreased . In the control group , no significant change in lipid profile was observed . CONCLUSIONS The results suggest that phase III cardiac rehabilitation could be beneficial for elderly patients with CAD In a controlled multicentre trial carried out to assess the value of long-term practolol treatment after myocardial infa rct ion the provisional results showed a significant reduction in mortality , though some of the data were lacking . These have now been included and the results up date d. The final figures for all deaths were 78 in the placebo group of 1533 patients and 48 in the practolol group of 1520 patients . The reduction in mortality ( 38 % ) was significant at the 1 % level . The figures for non-fatal reinfa rct ion ( 97 in the placebo group , and 75 in the practolol group ) were not significantly different . Patients with pre-entry anterior infa rct ion , and especially those with a diastolic blood pressure equal to or below the mean ( 78 mm Hg ) at entry to the trial , were at high risk but benefited particularly well from beta-adrenoceptor blockade . After pre-entry inferior infa rct ion the percentage reduction in deaths occurring within two hours after symptoms of a new event was similar to that after anterior infa rct ion , but the incidence of death more than two hours after the event was greater in the practolol-treated group . Thus the difference between groups in total deaths after pretrial inferior infa rct ion was marginal . Until the results of further trials are reported long-term beta-adrenoceptor blockade ( possibly up to two years ) is recommended after uncomplicated anterior myocardial infa rct ion BACKGROUND Physical activity contributes to improve health and quality of life . However , the prevalence of sedentary lifestyle is elevated after an acute coronary syndrome . METHODS A r and omized controlled trial was performed to evaluate the impact of a pedometer-based program associated with a socio-cognitive intervention on physical activity behaviour , cardiovascular risk factors , and quality of life during the year after an acute coronary syndrome event . During hospitalization , we r and omized 32 patients to an experimental group and 33 patients to a usual care group . The experimental intervention included 6 consultations with a clinical nurse specialist during 12 months . RESULTS Groups characteristics were comparable . At baseline , the percentage of participants considered in the active range category was similar between groups ( 31 % vs 41 % ; P = 0.915 ) . However , the proportion of participants who were still active was greater in the experimental group than in the usual care group at 6 , 9 , and 12 months follow-up ( 75 % vs 41 % ; 68 % vs 36 % , and 83 % vs 55 % , respectively ; P < 0.05 ) . After 12 months , changes in overall quality of life and in health and the functioning scores were different between groups ( interaction effects [ groups by time ] P = 0.048 and P = 0.036 , respectively ) . CONCLUSIONS The use of a pedometer concomitantly with a socio-cognitive intervention improves adherence to physical activity and quality of life during the year after an acute coronary syndrome event . This finding is relevant because physical activity and quality of life are a great concern in preventive cardiology . These results support applying this innovative approach in cardiac rehabilitation programs Aims To investigate the effects of exercise training ( ET ) on left ventricular ( LV ) volumes , cardiopulmonary functional capacity and N-terminal pro-brain natriuretic peptide ( NT-proBNP ) levels in postinfa rct ion patients with moderate LV dysfunction . Methods Sixty-one postinfa rct ion patients were r and omized into two groups : group T [ n = 30 , LV ejection fraction ( EF ) 41.6 ± 11.3 % , mean ± SD ] entered a 6-month ET programme , whereas group C ( n = 31 , EF 42.0 ± 7.6 % , P = NS ) did not . NT-proBNP assay , Doppler-echocardiography and cardiopulmonary exercise test were performed upon enrolment and at sixth months . Results At sixth months , trained patients showed an improvement in workload ( + 26 % , P<0.001 ) , Vo2peak ( + 31 % , P<0.001 ) , LV end-diastolic volume index ( LVEDVI ; −9 % , P<0.001 ) , a reduction in NT-proBNP ( −71 % , P<0.001 ) and a significant correlation between changes in NT-proBNP and in LVEDVI ( r=0.858 , P<0.001 ) . Baseline NT-proBNP correlated with changes in LVEDVI in both trained ( r=0.673 , P<0.001 ) and untrained ( r=0.623 , P<0.001 ) patients . Group C showed unfavourable LVEDVI dilation ( + 8 % , P<0.001 ; T vs. C group , P<0.001 ) and a smaller reduction in NT-proBNP ( −40 % , P<0.001 ; T vs. C group , P<0.001 ) . Conclusions Six month ET induced a favourable LV remodelling and a marked fall in NT-proBNP that could predict LV remodelling in postinfa rct ion patients with moderate LV dysfunction Patients are generally advised to return to full normal activities , including work , 6 to 8 weeks after acute myocardial infa rct ion ( AMI ) . We assessed the outcomes of early return to normal activities , including work at 2 weeks , after AMI in patients who were stratified to be at a low risk for future cardiac events . Patients were considered for r and omization before discharge if they had no angina , had left ventricular ejection fraction > 40 % , a negative result from a symptom-limited exercise stress test for ischemia ( < 2 mm ST depression ) at 1 week , and achieved > 7 METs . Patients with left ventricular ejection fraction < 40 % were included only if they did not have inducible ventricular tachycardia at electrophysiologic studies . Seventy-two patients were r and omized to return to normal activities at 2 weeks and 70 patients to undergo st and ard cardiac rehabilitation and return to normal activities at 6 weeks after AMI . There were no deaths or heart failure in either group . There was no significant difference in the incidence of reinfa rct ion , revascularization , left ventricular function , lipids , body mass index , smoking , or exercise test results at 6 months . In conclusion , return to full normal activities , including work at 2 weeks , after AMI appears to be safe in patients who are stratified to a low-risk group . This should have significant medical and socioeconomic implication Background Lifestyle measures of coronary heart disease ( CHD ) prevention have been overshadowed by the efficacy of drug treatments . This is particularly the case in the setting of secondary prevention where the benefits of lipid lowering , anti-platelet and anti-hypertensive drugs have been emphasised in numerous trials . Lifestyle measures address several CHD risk factors at once and are generally free of serious side effects . Objectives The objective of the present study was to determine whether a comprehensive programme of lifestyle modification could favourably influence dietary and exercise habits in addition to smoking cessation over two years . In addition , an attempt was made to evaluate if this programme could favourably influence the five-year CHD-risk in the male population included in the study . Design A total of 197 patients with proven coronary heart disease were included and r and omised to a lifestyle intervention programme or to usual care . Follow-up was after a period of two years . Methods Intervention comprised a low fat diet , regular exercise , smoking cessation , psychosocial support and education , delivered by nurses on the rationale for pharmacological and lifestyle measures . Usual care comprised follow-up in the routine outpatient clinic . Both groups were given the same comprehensive medication according to recent guidelines . Results Patients in the lifestyle intervention group reduced the intake of saturated fat , sugar and cholesterol ( P<0.001 ) , increased their exercise level ( P<0.01 ) and stopped smoking ( P<0.05 ) when compared with the usual care group . A sub analysis of the influence of five-year CHD calculated risk in males result ed in a relative risk reduction of 22 % ( 95 % confidence intervals 9 - 35 ) . Although significant , this result must be interpreted with caution due to poor statistical power and reproducibility of the method . Conclusions In the presence of modern drug treatments for secondary cardiovascular disease prevention it remains possible through a favourable diet , exercise and smoking cessation to show an additional reduction in the five-year risk for CHD in males Abstract The purpose of the trial was to analyze whether supervised physical training could reduce death and nonfatal reinfa rct ion in a nonselected series of postinfa rct patients . All patients born in 1913 and later , who were hospitalized for a myocardial infa rct ion during 1968–1970 in Goteborg Sweden , were r and omized to a training group ( 158 patients ) and a control group ( 157 patients ) . Other treatment was exactly the same and st and ardized for the two groups . Twenty-seven percent were excluded from training . Training started 3 months after the infa rct and was scheduled for three times a week . The training group had higher physical working capacity after 1 yr than the control group . Blood pressure was lower , but there was no differences in blood lipids . During 4 yr of follow-up , 28 patients died in the training group and 35 in the control group . The numbers of nonfatal reinfa rcts were 25 and 28 , respectively . Within the training group patients adhering to the program had lower mortality than those who did not , but the former also had lower initially predicted risk of dying . A special analysis of patients who attended the training program in comparison to matched controls also showed a lower mortality . No differences in mortality between the training group and the control group were statistically significant , however The results of a r and omized controlled trial of a single daily dose of acetyl salicylic acid ( aspirin ) in the prevention of reinfa rct ion in 1,239 men who had had a recent myocardial infa rct were statistically inconclusive . Nevertheless , they showed a reduction in total mortality of 12 % at six months and 25 % at twelve months after admission to the trial . Further trials are urgently required to establish whether or not this effect is real OBJECTIVE This study evaluated the effects of a home-based rehabilitation program for Chinese patients with myocardial infa rct ion in terms of health-related quality of life and psychological status . METHODS This was a r and omized , controlled trial with data collected at 2 university-affiliated public general hospitals in Xian ( Shaanxi Province , People 's Republic of China ) . One hundred and sixty patients with a myocardial infa rct ion were r and omly assigned to either the interventional group ( a home-based cardiac rehabilitation program using a self-help manual ) or the control group ( usual care ) . Health-related quality of life ( generic , Chinese Short Form 36-Item Health Survey ; disease-specific , Chinese Myocardial Infa rct ion Dimensional Assessment Scale ) and psychological status ( the Chinese Hospital Anxiety and Depression Scale ) were measured at baseline , program completion ( 6 weeks ) , and 3 and 6 months after hospital discharge . RESULTS Significant differences were evident in the main outcomes when the home-based group was compared with the usual care group at 6 weeks , 3 months , and 6 months . The home-based group had significantly higher scores on 4 of the 8 domains of the Chinese Short Form 36-Item Health Survey and on 3 of the 7 dimensions of the Chinese Myocardial Infa rct ion Dimensional Assessment Scale , with significantly lower scores on the anxiety , but not the depression , subscale of the Chinese Hospital Anxiety and Depression Scale . CONCLUSIONS A simple , home-based cardiac rehabilitation program for patients with acute myocardial infa rct ion , using a self-help manual , improves health-related quality of life and reduces anxiety . It appears feasible and acceptable , and does not produce inferior outcomes compared with usualcare in China |
13,828 | 24,382,358 | Strong evidence suggests that periodontitis is a risk factor for implant loss ; moderate evidence revealed that periodontitis is a risk factor for peri-implantitis and that patients with periodontitis have higher implant-bone loss | OBJECTIVE The aim of the present systematic review and meta- analysis was to assess the role of periodontal disease as a risk factor for implant loss , peri-implantitis and implant-bone loss . | BACKGROUND The aim of the present prospect i ve longitudinal study of periodontally diseased and periodontally healthy patients was a clinical , microbiological , and radiographic comparison of teeth and implants and an assessment of the implant success rate . METHODS Thirty-nine partially edentulous patients provided with a total of 150 implants were enrolled in the study . Oral rehabilitation was undertaken in 15 patients treated for generalized aggressive periodontitis ( GAgP ) , 12 patients treated for generalized chronic periodontitis ( GCP ) , and 12 periodontally healthy patients . The examinations of the teeth and implants were carried out within the framework of a 3-month recall schedule over a 3-year period . At each session , clinical parameters for probing depth ( PD ) , gingival recession ( GR ) , attachment level ( AL ) , gingival index ( GI ) , and plaque index ( PI ) were recorded , and the composition of the subgingival microflora determined by dark-field microscopy . In the periodontally diseased patients , Actinobacillus actinomycetemcomitans ( A.a . ) , Porphyromonas gingivalis ( P.g . ) , and Prevotella intermedia ( P.i . ) were detected at teeth and implants by DNA analysis in the first and third years after insertion of the superstructure . Intraoral radiographs of the teeth and implants were taken at baseline , immediately after insertion of the superstructure , and then 1 and 3 years later . RESULTS The GI and PI at implants and teeth remained below 0.25 and 0.6 , respectively , in all patient groups throughout the study period . At the implants and teeth , a slight increase in PD and a continuous attachment loss was recorded in the GAgP patients . The attachment loss was greater at the implants than at the teeth in all groups . The morphological distribution of the microorganisms revealed virtually healthy conditions in all groups . A.a . was detected in two GAgP patients , whereas P.g . and P.i . were found more frequently both in the GAgP and in the GCP patients . Radiographically detected bone loss was higher after 3 years at implants and teeth in the GAgP patients than in the other two groups . The implant success rates recorded were 100 % in the periodontally healthy and GCP patients , and 95.7 % in the maxilla and 100 % in the m and ible of the GAgP patients . CONCLUSIONS The results show that oral rehabilitation can be performed with implants in patients treated for generalized aggressive and chronic periodontitis . However , slight attachment loss and bone loss were registered at the implants and teeth in the patients with aggressive periodontitis OBJECTIVES To evaluate the long-term survival rates of dental implants according to the patient 's periodontal status , as well as to estimate if the effect of periodontal status regarding implant failure is constant throughout the long-term follow-up . MATERIAL S AND METHODS This was a historical prospect i ve cohort study design of all consecutive patients operated from 1996 to 2006 at a periodontal clinic . The cohort consisted of 736 patients , with a total of 2336 dental implants . An extended Cox proportional hazards model , which includes interaction terms between survival time and variables of interest , was used . RESULTS Patients ' mean ( SD ) age was 51.13 ( 12.35 ) . The follow-up time was up to 144 months , with a mean ( SD ) of 54.4 ( 35.6 ) months . The overall implant raw survival rate was 95.9 % . The Kaplan-Meier estimates for the cumulative survival rate ( CSR ) at 108 months were 0.96 and 0.95 for implants inserted into healthy and moderate chronic periodontal patients , respectively . The CSR declined to 0.88 at 108 months for the severe periodontitis group . The extended Cox model revealed that severe chronic status turned out to be a significant risk factor for implant failure after 50 months of follow-up [ hazard ratio (HR)=8.06 ; p<0.01 ] . The extended Cox model for smoking indicates a near-significant effect after 50 months ( HR=2.76 ; p=0.061 ) . CONCLUSIONS Periodontal status and smoking are significant risk factors for late implant failures . The HR for periodontal and smoking status are not constant throughout the follow-up period PURPOSE The purpose of this study was to analyze the current literature s and to assess outcomes of implant treatment in patients with generalized aggressive periodontitis . MATERIAL S AND METHODS Studies considered for inclusion were search ed in Pub-Med . The literature search for studies published in English between 2000 and 2012 was performed . Our findings included literature assessing implant treatment in patients with a history of generalized aggressive periodontitis ( GAP ) . All studies were screened according to inclusion criteria . The outcome measures were survival rate of superstructures , marginal bone loss around implant and survival rate of implants . All studies were divided into two follow-up period : short term study ( < 5 years ) and long term study ( ≥ 5 years ) . RESULTS Seven prospect i ve studies were selected , including four short-term and three long-term studies . The survival rates of the superstructures were generally high in patients with GAP , i.e. 95.9 - 100 % . Marginal bone loss around implant in patients with GAP as compared with implants in patients with chronic periodontitis or periodontally healthy patients was not significantly greater in short term studies but was significantly greater in long term studies . In short term studies , the survival rates of implants were between 97.4 % and 100 % in patients with GAP-associated tooth loss , except one study . The survival rates of implants were between 83.3 % and 96 % in patients with GAP in long term studies . CONCLUSION Implant treatment in patients with GAP is not contraindicated provided that adequate infection control and an individualized maintenance program are assured BACKGROUND The successful use of osseointegrated implants in periodontally healthy patients has been documented in numerous longitudinal studies in recent years . However , the extent to which these positive results apply to periodontally diseased patients remains unclear . The aim of the present prospect i ve longitudinal study of partially edentulous patients treated for generalized chronic periodontitis and generalized aggressive periodontitis was a clinical , microbiological , and radiographic comparison of teeth and implants and assessment of the implant success rate . METHODS Five partially edentulous patients treated for generalized aggressive periodontitis ( GAgP ) and 5 treated for generalized chronic periodontitis ( GCP ) were enrolled in this study . The GAgP patients received 36 implants , and the GCP patients 12 implants . The teeth were examined 2 to 4 weeks before extraction of the non-retainable teeth ( baseline ) , and 3 weeks after insertion of the final abutments ( second examination ) . All further examinations were performed during a 3-month recall schedule over a 5-year period for the GAgP patients and over a 3-year period for the GCP patients . At each session clinical parameters were recorded at teeth and implants and the composition of the subgingival microflora was determined by dark-field microscopy and DNA analysis . Intraoral radiographs of the teeth and implants were taken for control purpose s at baseline ; after insertion of the superstructure ; and 1 , 3 , and 5 years later . RESULTS The clinical findings indicated healthy periodontal and peri-implant conditions in both patient groups throughout the study . However , an increased probing depth and an attachment loss were recorded in the GAgP patients after the third year ( P<0.001 ) . The distribution of the microorganisms revealed no significant differences between the patient groups or between implants and teeth . Moderate bone loss at teeth and implants was registered in both groups . The success rates recorded were 100 % in the GCP patients and 88.8 % ( maxilla : 85.7 % ; m and ible : 93.3 % ) in the GAgP patients . CONCLUSIONS The 3-year and 5-year follow-ups show that osseointegrated implants may be successful in oral rehabilitation of partially edentulous patients treated for generalized aggressive periodontitis and generalized chronic periodontitis . However , as no significant differences were recorded between conditions at teeth and at implants , progression of the disease can not be ruled out BACKGROUND The aim of this prospect i ve 10-year study of partially edentulous subjects treated for generalized aggressive periodontitis and periodontally healthy subjects was a clinical , microbiologic , and radiographic comparison of teeth and implants and assessment of the implants ' success rate . METHODS Five subjects treated for generalized aggressive periodontitis ( GAgP ) and five periodontally healthy subjects who were orally rehabilitated with osseointegrated implants participated in the study . First , they were examined 2 to 4 weeks before extraction of the non-retainable teeth ( baseline ) and 3 weeks after insertion of the final abutments . All further examinations were performed during a 3-month recall schedule over a 10-year period . At every session , clinical parameters were recorded , and the composition of the subgingival microflora was determined . Radiographs were taken at baseline after insertion of the superstructure and 1 , 3 , 5 , 8 , and 10 years later . RESULTS Throughout the follow-up period , the peri-implant gingival index of GAgP subjects was significantly higher than in periodontally healthy subjects . There was no difference in plaque index between teeth and implants or between the two groups . The peri-implant probing depths were comparable in the two groups and remained < or = 4 mm throughout the follow-up . The probing depth was significantly higher around the teeth of the GAgP subjects compared to periodontally healthy subjects . Implants of GAgP subjects showed a significantly higher attachment loss ( Ø 2.4 mm ) . The attachment level at teeth and implants of the periodontally healthy subjects and at teeth of the GAgP subjects was almost unchanged . Microbiologically , GAgP subjects had fewer cocci and more motile rods and filaments at teeth and implants than periodontally healthy subjects . GAgP subjects showed significantly more peri-implant bone loss in the first year ( Ø 2.07 mm ) and in the subsequent 9 years ( total 1.3 mm ) . Bone loss at teeth also was significantly higher at baseline ( Ø 26.39 % ) and in the following years ( total 9.3 % ) . Implant survival rates were 100 % in periodontally healthy subjects versus 83.33 % in GAgP subjects . CONCLUSIONS This 10-year study showed that partially edentulous subjects treated for GAgP can be rehabilitated successfully with osseointegrated implants . However , the bone and attachment loss at the implants were higher than in periodontally healthy subjects This study evaluated the efficacy of implant supported dental restorations in patients with chronic periodontal diseases at various stages within 2 years of completing treatment . 30 patients with periodontal diseases and 30 patients without periodontal diseases were studied . Total counts of 276 implant bodies were divided into group A ( patients with periodontal diseases ; a total of 149 implants ) and group B ( patients with healthy periodontium ; a total of 127 implants ) . In group A subjects , periodontitis was treated prior to implant placement . The study focused on patients ' modified sulcus bleeding index , modified plaque index , implant mobility index , periodontal probing depth and implant success rate 12 and 24 months after the completion of the treatment . The result show : there were no significant differences in implant success rate between groups A and B ; modified sulcus bleeding index scores showed differences between the groups 24 months after treatment ; there were no significant differences in other clinical indexes during the study between the groups ; there were no significant differences in periodontal probing depth between the groups ; modified plaque index and modified sulcus bleeding index were positively correlated in implant supported dental restoration patients with chronic periodontal diseases |
13,829 | 28,442,405 | Exergames improved cognition in both clinical and non‐ clinical population s .
Significant effects were found executive functions , attention and visuospatial skills .
Significant effects still existed when excluding waitlist‐only controlled studies , and when comparing to physical activity interventions .
Domain‐specific analyses found exergames improved executive functions , attentional processing and visuospatial skills .
The findings present the first meta‐analytic evidence for effects of exergames on cognition . | HighlightsThis is the first meta‐ analysis of active video games ( ‘ exergames ’ ) for cognition .
Abstract Physically‐active video games ( ‘ exergames ’ ) have recently gained popularity for leisure and entertainment purpose s. Using exergames to combine physical activity and cognitively‐dem and ing tasks may offer a novel strategy to improve cognitive functioning . | Background Stepping impairments are associated with physical and cognitive decline in older adults and increased fall risk . Exercise interventions can reduce fall risk , but adherence is often low . A new exergame involving step training may provide an enjoyable exercise alternative for preventing falls in older people . Purpose To assess the feasibility and safety of unsupervised , home-based step pad training and determine the effectiveness of this intervention on stepping performance and associated fall risk in older people . Design Single-blinded two-arm r and omized controlled trial comparing step pad training with control ( no-intervention ) . Setting / Participants Thirty-seven older adults residing in independent-living units of a retirement village in Sydney , Australia . Intervention Intervention group ( IG ) participants were provided with a computerized step pad system connected to their TVs and played a step game as often as they liked ( with a recommended dose of 2–3 sessions per week for 15–20 minutes each ) for eight weeks . In addition , IG participants were asked to complete a choice stepping reaction time ( CSRT ) task once each week . Main Outcome Measures CSRT , the Physiological Profile Assessment ( PPA ) , neuropsychological and functional mobility measures were assessed at baseline and eight week follow-up . Results Thirty-two participants completed the study ( 86.5 % ) . IG participants played a median 2.75 sessions/week and no adverse events were reported . Compared to the control group , the IG significantly improved their CSRT ( F31,1 = 18.203 , p<.001 ) , PPA composite scores ( F31,1 = 12.706 , p = 0.001 ) , as well as the postural sway ( F31,1 = 4.226 , p = 0.049 ) and contrast sensitivity ( F31,1 = 4.415 , p = 0.044 ) PPA sub-component scores . In addition , the IG improved significantly in their dual-task ability as assessed by a timed up and go test/verbal fluency task ( F31,1 = 4.226 , p = 0.049 ) . Conclusions Step pad training can be safely undertaken at home to improve physical and cognitive parameters of fall risk in older people without major cognitive and physical impairments . Trial Registration Australian New Zeal and Clinical Trials Registry ACTRN12611001081909 Different types of exercise training have the potential to induce structural and functional brain plasticity in the elderly . Thereby , functional brain adaptations were observed during cognitive tasks in functional magnetic resonance imaging studies that correlated with improved cognitive performance . This study aim ed to investigate if exercise training induces functional brain plasticity during challenging treadmill walking and elicits associated changes in cognitive executive functions . Forty-two elderly participants were recruited and r and omly assigned to either interactive cognitive-motor video game dancing ( DANCE ) or balance and stretching training ( BALANCE ) . The 8-week intervention included three sessions of 30 min per week and was completed by 33 participants ( mean age 74.9 ± 6.9 years ) . Prefrontal cortex ( PFC ) activity during preferred and fast walking speed on a treadmill was assessed applying functional near infrared spectroscopy pre- and post-intervention . Additionally , executive functions comprising shifting , inhibition , and working memory were assessed . The results showed that both interventions significantly reduced left and right hemispheric PFC oxygenation during the acceleration of walking ( p < 0.05 or trend , r = 0.25–0.36 ) , while DANCE showed a larger reduction at the end of the 30-s walking task compared to BALANCE in the left PFC [ F(1 , 31 ) = 3.54 , p = 0.035 , r = 0.32 ] . These exercise training induced modulations in PFC oxygenation correlated with improved executive functions ( p < 0.05 or trend , r = 0.31–0.50 ) . The observed reductions in PFC activity may release cognitive re sources to focus attention on other processes while walking , which could be relevant to improve mobility and falls prevention in the elderly . This study provides a deeper underst and ing of the associations between exercise training , brain function during walking , and cognition in older adults Cognitive control is defined by a set of neural processes that allow us to interact with our complex environment in a goal -directed manner . Humans regularly challenge these control processes when attempting to simultaneously accomplish multiple goals ( multitasking ) , generating interference as the result of fundamental information processing limitations . It is clear that multitasking behaviour has become ubiquitous in today ’s technologically dense world , and substantial evidence has accrued regarding multitasking difficulties and cognitive control deficits in our ageing population . Here we show that multitasking performance , as assessed with a custom- design ed three-dimensional video game ( NeuroRacer ) , exhibits a linear age-related decline from 20 to 79 years of age . By playing an adaptive version of NeuroRacer in multitasking training mode , older adults ( 60 to 85 years old ) reduced multitasking costs compared to both an active control group and a no-contact control group , attaining levels beyond those achieved by untrained 20-year-old participants , with gains persisting for 6 months . Furthermore , age-related deficits in neural signatures of cognitive control , as measured with electroencephalography , were remediated by multitasking training ( enhanced midline frontal theta power and frontal – posterior theta coherence ) . Critically , this training result ed in performance benefits that extended to untrained cognitive control abilities ( enhanced sustained attention and working memory ) , with an increase in midline frontal theta power predicting the training-induced boost in sustained attention and preservation of multitasking improvement 6 months later . These findings highlight the robust plasticity of the prefrontal cognitive control system in the ageing brain , and provide the first evidence , to our knowledge , of how a custom- design ed video game can be used to assess cognitive abilities across the lifespan , evaluate underlying neural mechanisms , and serve as a powerful tool for cognitive enhancement Exergames are videogames that require gross motor activity , thereby combining gaming with physical activity . This study examined the role of competitive versus cooperative exergame play on short-term changes in executive function skills , following a 10-week exergame training intervention . Fifty-four low-income overweight and obese African American adolescents were r and omly assigned to a competitive exergame condition , a cooperative exergame condition , or a no-play control group . Youths in the competitive exergame condition improved in executive function skills more than did those in the cooperative exergame condition and the no-play control group . Weight loss during the intervention was also significantly positively correlated with improved executive function skills . The findings link competitive exergame play to beneficial cognitive outcomes for at-risk ethnic minority adolescents Aging is usually accompanied with deterioration of physical abilities , such as muscular strength , sensory sensitivity , and functional capacity . Recently , intervention methods with virtual reality have been introduced , providing an enjoyable therapy for elderly . The aim of this study was to investigate whether a 3-D virtual reality kayak program could improve the cognitive function , muscle strength , and balance of community-dwelling elderly . Importantly , kayaking involves most of the upper body musculature and needs the balance control . Seventy-two participants were r and omly allocated into the kayak program group ( n = 36 ) and the control group ( n = 36 ) . The two groups were well matched with respect to general characteristics at baseline . The participants in both groups performed a conventional exercise program for 30 min , and then the 3-D virtual reality kayak program was performed in the kayak program group for 20 min , two times a week for 6 weeks . Cognitive function was measured using the Montreal Cognitive Assessment . Muscle strength was measured using the arm curl and h and grip strength tests . St and ing and sitting balance was measured using the Good Balance system . The post-test was performed in the same manner as the pre-test ; the overall outcomes such as cognitive function ( p < 0.05 ) , muscle strength ( p < 0.05 ) , and balance ( st and ing and sitting balance , p < 0.05 ) were significantly improved in kayak program group compared to the control group . We propose that the 3-D virtual reality kayak program is a promising intervention method for improving the cognitive function , muscle strength , and balance of elderly Background Cognitive impairment is a health problem that concerns almost every second elderly person . Physical and cognitive training have differential positive effects on cognition , but have been rarely applied in combination . This study evaluates synergistic effects of multicomponent physical exercise complemented with novel simultaneous cognitive training on cognition in older adults . We hypothesized that simultaneous cognitive – physical components would add training specific cognitive benefits compared to exclusively physical training . Methods Seniors , older than 70 years , without cognitive impairment , were r and omly assigned to either : 1 ) virtual reality video game dancing ( DANCE ) , 2 ) treadmill walking with simultaneous verbal memory training ( MEMORY ) , or 3 ) treadmill walking ( PHYS ) . Each program was complemented with strength and balance exercises . Two 1-hour training sessions per week over 6 months were applied . Cognitive performance was assessed at baseline , after 3 and 6 months , and at 1-year follow-up . Multiple regression analyses with planned comparisons were calculated . Results Eighty-nine participants were r and omized to the three groups initially , 71 completed the training , while 47 were available at 1-year follow-up . Advantages of the simultaneous cognitive – physical programs were found in two dimensions of executive function . “ Shifting attention ” showed a time × intervention interaction in favor of DANCE/MEMORY versus PHYS ( F[2 , 68 ] = 1.95 , trend P=0.075 , r=0.17 ) ; and “ working memory ” showed a time × intervention interaction in favor of DANCE versus MEMORY ( F[1 , 136 ] = 2.71 , trend P=0.051 , R2=0.006 ) . Performance improvements in executive functions , long-term visual memory ( episodic memory ) , and processing speed were maintained at follow-up in all groups . Conclusion Particular executive functions benefit from simultaneous cognitive – physical training compared to exclusively physical multicomponent training . Cognitive – physical training programs may counteract widespread cognitive impairments in the elderly 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 hippocampus shrinks in late adulthood , leading to impaired memory and increased risk for dementia . Hippocampal and medial temporal lobe volumes are larger in higher-fit adults , and physical activity training increases hippocampal perfusion , but the extent to which aerobic exercise training can modify hippocampal volume in late adulthood remains unknown . Here we show , in a r and omized controlled trial with 120 older adults , that aerobic exercise training increases the size of the anterior hippocampus , leading to improvements in spatial memory . Exercise training increased hippocampal volume by 2 % , effectively reversing age-related loss in volume by 1 to 2 y. We also demonstrate that increased hippocampal volume is associated with greater serum levels of BDNF , a mediator of neurogenesis in the dentate gyrus . Hippocampal volume declined in the control group , but higher preintervention fitness partially attenuated the decline , suggesting that fitness protects against volume loss . Cau date nucleus and thalamus volumes were unaffected by the intervention . These theoretically important findings indicate that aerobic exercise training is effective at reversing hippocampal volume loss in late adulthood , which is accompanied by improved memory function BACKGROUND Age-associated motor and cognitive deficits increase the risk of falls , a major cause of morbidity and mortality . Because of the significant ramifications of falls , many interventions have been proposed , but few have aim ed to prevent falls via an integrated approach targeting both motor and cognitive function . We aim ed to test the hypothesis that an intervention combining treadmill training with non-immersive virtual reality ( VR ) to target both cognitive aspects of safe ambulation and mobility would lead to fewer falls than would treadmill training alone . METHODS We carried out this r and omised controlled trial at five clinical centres across five countries ( Belgium , Israel , Italy , the Netherl and s , and the UK ) . Adults aged 60 - 90 years with a high risk of falls based on a history of two or more falls in the 6 months before the study and with varied motor and cognitive deficits were r and omly assigned by use of computer-based allocation to receive 6 weeks of either treadmill training plus VR or treadmill training alone . R and omisation was stratified by subgroups of patients ( those with a history of idiopathic falls , those with mild cognitive impairment , and those with Parkinson 's disease ) and sex , with stratification per clinical site . Group allocation was done by a third party not involved in onsite study procedures . Both groups aim ed to train three times per week for 6 weeks , with each session lasting about 45 min and structured training progression individualised to the participant 's level of performance . The VR system consisted of a motion-capture camera and a computer-generated simulation projected on to a large screen , which was specifically design ed to reduce fall risk in older adults by including real-life challenges such as obstacles , multiple pathways , and distracters that required continual adjustment of steps . The primary outcome was the incident rate of falls during the 6 months after the end of training , which was assessed in a modified intention-to-treat population . Safety was assessed in all patients who were assigned a treatment . This study is registered with Clinical Trials.gov , NCT01732653 . FINDINGS Between Jan 6 , 2013 , and April 3 , 2015 , 302 adults were r and omly assigned to either the treadmill training plus VR group ( n=154 ) or treadmill training alone group ( n=148 ) . Data from 282 ( 93 % ) participants were included in the prespecified , modified intention-to-treat analysis . Before training , the incident rate of falls was similar in both groups ( 10·7 [ SD 35·6 ] falls per 6 months for treadmill training alone vs 11·9 [ 39·5 ] falls per 6 months for treadmill training plus VR ) . In the 6 months after training , the incident rate was significantly lower in the treadmill training plus VR group than it had been before training ( 6·00 [ 95 % CI 4·36 - 8·25 ] falls per 6 months ; p<0·0001 vs before training ) , whereas the incident rate did not decrease significantly in the treadmill training alone group ( 8·27 [ 5·55 - 12·31 ] falls per 6 months ; p=0·49 ) . 6 months after the end of training , the incident rate of falls was also significantly lower in the treadmill training plus VR group than in the treadmill training group ( incident rate ratio 0·58 , 95 % CI 0·36 - 0·96 ; p=0·033 ) . No serious training-related adverse events occurred . INTERPRETATION In a diverse group of older adults at high risk for falls , treadmill training plus VR led to reduced fall rates compared with treadmill training alone . FUNDING European Commission During aging , the prefrontal cortex ( PFC ) undergoes age-dependent neuronal changes influencing cognitive and motor functions . Motor-learning interventions are hypothesized to ameliorate motor and cognitive deficits in older adults . Especially , video game-based physical exercise might have the potential to train motor in combination with cognitive abilities in older adults . The aim of this study was to compare conventional balance training with video game-based physical exercise , a so-called exergame , on the relative power ( RP ) of electroencephalographic ( EEG ) frequencies over the PFC , executive function ( EF ) , and gait performance . Twenty-seven participants ( mean age 79.2 ± 7.3 years ) were r and omly assigned to one of two groups . All participants completed 24 trainings including three times a 30 min session/week . The EEG measurements showed that theta RP significantly decreased in favor of the exergame group [ L(14 ) = 6.23 , p = 0.007 ] . Comparing pre- vs. post-test , EFs improved both within the exergame ( working memory : z = −2.28 , p = 0.021 ; divided attention auditory : z = −2.51 , p = 0.009 ; divided attention visual : z = −2.06 , p = 0.040 ; go/no-go : z = −2.55 , p = 0.008 ; set-shifting : z = −2.90 , p = 0.002 ) and within the balance group ( set-shifting : z = −2.04 , p = 0.042 ) . Moreover , spatio-temporal gait parameters primarily improved within the exergame group under dual-task conditions ( speed normal walking : z = −2.90 , p = 0.002 ; speed fast walking : z = −2.97 , p = 0.001 ; cadence normal walking : z = −2.97 , p = 0.001 ; stride length fast walking : z = −2.69 , p = 0.005 ) and within the balance group under single-task conditions ( speed normal walking : z = −2.54 , p = 0.009 ; speed fast walking : z = −1.98 , p = 0.049 ; cadence normal walking : z = −2.79 , p = 0.003 ) . These results indicate that exergame training as well as balance training positively influence prefrontal cortex activity and /or function in varying proportion We investigated the training effects and transfer effects associated with 2 approaches to cognitive activities ( so-called brain training ) that might mitigate age-related cognitive decline . A sample of 78 adults between the ages of 50 and 71 completed 20 one-hr training sessions with the Nintendo Wii Big Brain Academy software over the course of 1 month and , in a second month , completed 20 one-hr reading sessions with articles on 4 different current topics ( order of assignment was counterbalanced for the participants ) . An extensive battery of cognitive and perceptual speed ability measures was administered before and after each month of cognitive training activities , along with a battery of domain-knowledge tests . Results indicated substantial improvements on the Wii tasks , somewhat less improvement on the domain knowledge tests , and practice -related improvements on 6 of the 10 ability tests . However , there was no significant transfer of training from either the Wii practice or the reading tasks to measures of cognitive and perceptual speed abilities . Implication s for these findings are discussed in terms of adult intellectual development and maintenance OBJECTIVE To examine the effect of the adapted virtual reality cognitive training program in older adults with chronic schizophrenia . METHODS Older adults with chronic schizophrenia were recruited from a long-stay care setting and were r and omly assigned into intervention ( n = 12 ) and control group ( n = 15 ) . The intervention group received 10-session of VR program that consisted of 2 VR activities using IREX . The control group attended the usual programs in the setting . RESULTS After the 10-session intervention , older adults with chronic schizophrenia preformed significantly better than control in overall cognitive function ( p .000 ) , and in two cognitive subscales : repetition ( p .001 ) and memory ( p .040 ) . These participants engaged in the VR activities volitionally . No problem of cybersickness was observed . CONCLUSIONS The results of the current study indicate that engaging in the adapted virtual reality cognitive training program offers the potential for significant gains in cognitive function of the older adults with chronic schizophrenia OBJECTIVE We evaluated the feasibility of a trial of Wii interactive video gaming , and its potential efficacy at improving cognitive functioning compared with health education , in a community sample of older adults with neuropsychologically defined mild cognitive impairment . METHODS Twenty older adults were equally r and omized to either group-based interactive video gaming or health education for 90 min each week for 24 weeks . Although the primary outcomes were related to study feasibility , we also explored the effect of the intervention on neuropsychological performance and other secondary outcomes . RESULTS All 20 participants completed the intervention , and 18 attended at least 80 % of the sessions . The majority ( 80 % ) of participants were " very much " satisfied with the intervention . Bowling was enjoyed by the most participants and was also rated the highest among the games for mental , social , and physical stimulation . We observed medium effect sizes for cognitive and physical functioning in favor of the interactive video gaming condition , but these effects were not statistically significant in this small sample . CONCLUSION Interactive video gaming is feasible for older adults with mild cognitive impairment , and medium effect sizes in favor of the Wii group warrant a larger efficacy trial Dementia cases are increasing worldwide ; thus , investigators seek to identify interventions that might prevent or ameliorate cognitive decline in later life . Extensive research confirms the benefits of physical exercise for brain health , yet only a fraction of older adults exercise regularly . Interactive mental and physical exercise , as in aerobic exergaming , not only motivates , but has also been found to yield cognitive benefit above and beyond traditional exercise . This pilot study sought to investigate whether greater cognitive challenge while exergaming would yield differential outcomes in executive function and generalize to everyday functioning . Sixty-four community based older adults ( mean age=82 ) were r and omly assigned to pedal a stationary bike , while interactively engaging on-screen with : ( 1 ) a low cognitive dem and task ( bike tour ) , or ( 2 ) a high cognitive dem and task ( video game ) . Executive function ( indices from Trails , Stroop and Digit Span ) was assessed before and after a single-bout and 3-month exercise intervention . Significant group × time interactions were found after a single-bout ( Color Trails ) and after 3 months of exergaming ( Stroop ; among 20 adherents ) . Those in the high cognitive dem and group performed better than those in the low cognitive dose condition . Everyday function improved across both exercise conditions . Pilot data indicate that for older adults , cognitive benefit while exergaming increased concomitantly with higher doses of interactive mental challenge Individuals with schizophrenia display substantial neurocognitive deficits for which available treatments offer only limited benefits . Yet , findings from studies of animals , clinical and non clinical population s have linked neurocognitive improvements to increases in aerobic fitness ( AF ) via aerobic exercise training ( AE ) . Such improvements have been attributed to up-regulation of brain-derived neurotrophic factor ( BDNF ) . However , the impact of AE on neurocognition , and the putative role of BDNF , have not been investigated in schizophrenia . Employing a proof-of-concept , single-blind , r and omized clinical trial design , 33 individuals with schizophrenia were r and omized to receive st and ard psychiatric treatment ( n = 17 ; " treatment as usual " ; TAU ) or attend a 12-week AE program ( n = 16 ) utilizing active-play video games ( Xbox 360 Kinect ) and traditional AE equipment . Participants completed assessment s of AF ( indexed by VO2 peak ml/kg/min ) , neurocognition ( MATRICS Consensus Cognitive Battery ) , and serum-BDNF before and after and 12-week period . Twenty-six participants ( 79 % ) completed the study . At follow-up , the AE participants improved their AF by 18.0 % vs a -0.5 % decline in the TAU group ( P = .002 ) and improved their neurocognition by 15.1 % vs -2.0 % decline in the TAU group ( P = .031 ) . Hierarchical multiple regression analyses indicated that enhancement in AF and increases in BDNF predicted 25.4 % and 14.6 % of the neurocognitive improvement variance , respectively . The results indicate AE is effective in enhancing neurocognitive functioning in people with schizophrenia and provide preliminary support for the impact of AE-related BDNF up-regulation on neurocognition in this population . Poor AF represents a modifiable risk factor for neurocognitive dysfunction in schizophrenia for which AE training offer a safe , nonstigmatizing , and side-effect-free intervention Dementia cases are on the rise and research ers seek innovative ways to prevent or ameliorate cognitive impairment in later life . Some research has reported that combining mental and physical exercise may benefit cognition more than either alone . This r and omized pilot trial examined the feasibility and cognitive benefit for older adults ( n = 30 ) of a single bout of neuro-exergaming ( physical activity with cognitive training ) using an interactive physical and cognitive exercise system ( iPACES ) , compared with that of exergaming or neurogaming alone . Intent-to-treat and sensitivity analyses were conducted using repeated- measures ANOVA , controlling for age , sex , and education . A significant interaction effect was found for executive function ( Color Trails 2 ) , with a significant improvement in the neuro-exergaming condition . Results demonstrate feasibility for older adults to use a novel and theoretically-derived neuro-exergame , and also provide promising new evidence that neuro-exergaming can yield greater cognitive benefit than either of its component parts |
13,830 | 24,370,277 | Besides , negative Bcl-2 expression was significantly associated with good OR and pathological CR in anthracycline-based chemotherapy subgroup .
Furthermore , there were significant links between negative Bcl-2 expression and taxane-based chemotherapy with pathological CR , but not OR .
Conclusion The results of the present meta- analysis suggest that Bcl-2 expression is a predictive factor for chemotherapy sensitivity in breast cancer patients .
They could also potentially benefit further clinical treatment for breast cancers | Background Numerous studies have yielded inconclusive results regarding the relationship between anti-apoptotic protein Bcl-2 expression and the sensitivity to chemotherapy in the patients with breast cancer .
The purpose of the current study was therefore to elaborate their relationship . | Introduction To investigate the predictive value of clinical and biological markers for a pathological complete remission after a preoperative dose-dense regimen of doxorubicin and docetaxel , with or without tamoxifen , in primary operable breast cancer . Methods Patients with a histologically confirmed diagnosis of previously untreated , operable , and measurable primary breast cancer ( tumour ( T ) , nodes ( N ) and metastases ( M ) score : T2 - 3(≥ 3 cm ) N0 - 2 M0 ) were treated in a prospect ively r and omised trial with four cycles of dose-dense ( bi-weekly ) doxorubicin and docetaxel ( ddAT ) chemotherapy , with or without tamoxifen , prior to surgery . Clinical and pathological parameters ( menopausal status , clinical tumour size and nodal status , grade , and clinical response after two cycles ) and a panel of biomarkers ( oestrogen and progesterone receptors , Ki-67 , human epidermal growth factor receptor 2 ( HER2 ) , p53 , bcl-2 , all detected by immunohistochemistry ) were correlated with the detection of a pathological complete response ( pCR ) . Results A pCR was observed in 9.7 % in 248 patients r and omised in the study and in 8.6 % in the subset of 196 patients with available tumour tissue . Clinical ly negative axillary lymph nodes , poor tumour differentiation , negative oestrogen receptor status , negative progesterone receptor status , and loss of bcl-2 were significantly predictive for a pCR in a univariate logistic regression model , whereas in a multivariate analysis only the clinical nodal status and hormonal receptor status provided significantly independent information . Backward stepwise logistic regression revealed a response after two cycles , with hormone receptor status and lymph-node status as significant predictors . Patients with a low percentage of cells stained positive for Ki-67 showed a better response when treated with tamoxifen , whereas patients with a high percentage of Ki-67 positive cells did not have an additional benefit when treated with tamoxifen . Tumours overexpressing HER2 showed a similar response to that in HER2-negative patients when treated without tamoxifen , but when HER2-positive tumours were treated with tamoxifen , no pCR was observed . Conclusion Reliable prediction of a pathological complete response after preoperative chemotherapy is not possible with clinical and biological factors routinely determined before start of treatment . The response after two cycles of chemotherapy is a strong but dependent predictor . The only independent factor in this subset of patients was bcl-2.Trial registration Our aim was to determine whether biological molecular markers can predict response to neoadjuvant chemoendocrine therapy in patients with early breast cancer . Ninety patients ( median age 56 years ; range , 28 - 69 years ) with primary operable breast carcinoma were studied . They were treated with four 3-weekly cycles of chemotherapy with mitozantrone , methotrexate ( + /- mitomycin C ) , and tamoxifen prior to surgery . Fine-needle aspiration was used to obtain sample s from patients prior to therapy , and the following parameters were assessed : estrogen receptor ( ER ) , progesterone receptor ( PgR ) , p53 , Ki67 , Bcl-2 , and c-erbB-2 measured by immunocytochemistry , and ploidy and S-phase fraction ( SPF ) by flow cytometry . The tumors of 78 % of the subjects responded ( complete response , 9 % ; partial response , 69 % ) and 22 % did not ( no change , 20 % ; progressive disease , 2 % ) . Response rates according to disease stage and patient age were as follows : T1 , 74 % ; T2 , 79 % ; T3/T4 , 78 % ; age < /=50 years , 76 % ; > 50 , 79 % ( P = not significant ) . Response rates for other parameters were as follows : ER-positive , 82 % , and -negative , 70 % ; PgR-positive , 86 % , and -negative , 71 % ; p53-positive , 74 % , and -negative , 81 % ; Bcl-2-positive , 85 % , and -negative 61 % ; c-erbB-2-positive , 57 % , and -negative , 93 % ; Ki67 high , 77 % , and low , 81 % ; SPF high , 77 % , and low , 77 % ; aneuploid , 71 % ; and diploid , 85 % . Only the difference for c-erbB-2 was statistically significant ( P = 0.007 ) . A trend for higher response rates to neoadjuvant chemoendocrine therapy for tumors that were positive for ER , PgR , and Bcl-2 was observed but did not reach statistical significance . Tumors negative for c-erbB-2 had a higher response rate , which was statistically significant . In contrast , Ki67 , ploidy , SPF , and p53 failed to predict for response INTRODUCTION Response to neoadjuvant chemotherapy for locally advanced breast cancer can be correlated with long-term outcomes . Surrogate end-point biomarkers may be used to assess response to the treatment . Most reported studies assessed the effects of combination chemotherapy . We assessed the feasibility of obtaining serial core breast biopsies , and correlated rates of apoptosis , proliferation , and expression of related proteins at baseline , during , and after neoadjuvant single agent chemotherapy for locally advanced breast cancer with response . EXPERIMENTAL DESIGN Women with a histologically confirmed unresected T(3 ) or T(4 ) infiltrating carcinoma of the breast were eligible . The first 20 patients received three cycles of doxorubicin 90 mg/m(2 ) followed by three cycles of paclitaxel 250 mg/m(2 ) , or the reverse . Nine women received four cycles of each ( doxorubicin 60 mg/m(2 ) and paclitaxel 175 mg/m(2 ) ) . Cycles were administered 14 days apart with filgastrim . End points included : ( a ) . clinical and pathological response ; ( b ) . serial apoptotic [ terminal deoxynucleotidyl transferase (Tdt)-mediated nick end labeling ] and proliferation ( immunohistochemistry , IHC ) rates ; and ( c ) . expression ( IHC ) of estrogen receptor , HER2 , bcl2 , and p53 . RESULTS From April 1997 to June 2001 , 29 women were r and omized . Twelve patients ( 42 % ) had a clinical complete response ( cCR ) , and 16 ( 55 % ) had a clinical partial response . Five women ( 17 % ) had a pathological complete response , 7 ( 24 % ) had microscopic residual disease , and 17 ( 58 % ) had macroscopic residual disease . Higher baseline apoptosis and proliferation were associated with an improved pathological response ( P = 0.006 and 0.003 , respectively ) . Among 14 evaluable patients , apoptosis increased in women who had a cCR to the first agent but not in women without a cCR . Estrogen receptor-positive patients had a worse pathological response ( P = 0.004 ) . CONCLUSIONS The selected regimen is efficacious . It is feasible to obtain serial core biopsies that are informative for studies of apoptosis and IHC . This clinical design can serve as a model for combining st and ard chemotherapy and novel agents BACKGROUND Biological considerations support the use of primary chemotherapy in operable breast cancer ; and despite wide variations of used regimens , clinical studies consistently show a significant tumor response allowing breast conservation in many patients otherwise c and i date s for mastectomy . We investigated the efficacy and the acceptance of a combination chemotherapy with vinorelbine , 5-fluorouracil and high-dose folinic acid in operable breast cancer with favorable prognostic factors and tested the relationship of hormone receptor status , Ki67,p53 , c-erbB2 and bcl-2 with treatment response . PATIENTS AND METHODS Thirty-nine patients ( median age 51 years , range 36 - 71 years ) , eight with T1 , twenty-eight with T2 and two with T3 lesions , were treated with 5-fluorouracil ( 350 mg/m2 , i.v . on day 1 to 3 ) preceded by folinic acid ( 100 mg/m2 i.v . on day 1 to 3 ) and vinorelbine , given on days 1 and 3 at the dose of 20 mg/m2 ( FLN regimen ) . Therapy was administered on an outpatient basis every three weeks . Non responders had surgery after three courses , while complete or partial responders underwent surgery after six courses . All but one were evaluable for response and toxicity . RESULTS Objective responses were observed in 23 of the 38 evaluable patients ( 61 % ; 95 % CI : 46%-76 % ) : three complete responses ( 8 % ) and 20 partial responses ( 53 % ) . Fifteen patients ( 39 % ) had stable disease , of whom nine ( 23 % ) had minor response . None of the patients had disease progression during treatment . Objective responses were significantly associated with no expression of estrogen and /or progesterone receptors and > 50 % decrease in Ki67 after induction chemotherapy . Tolerance was excellent and none of the patients experienced grade 2 alopecia . CONCLUSIONS The ' moderate ' efficacy of this regimen might be partially due to the selection of patients with high expression of steroid hormone receptors and low proliferation rate , which have an unfavorable impact on response to this chemotherapy Aim : To evaluate the relationship between apoptosis induced by chemotherapy and clinical response in breast cancer . Methods : Apoptosis index ( AI ) , mutant p53 and Bcl‐2 protein expression were evaluated in 44 breast tumour sample s from patients su bmi tted to neoadjuvant chemotherapy . Objective response ( OR ) to primary chemotherapy was observed in 37 patients ( 84 % ) and no response ( NR ) in seven . AI was measured by the rate of apoptotic cells identified using morphological criteria . p53 and Bcl‐2 protein expression were evaluated using an immunoperoxidase staining technique . Results : The median AI change observed between pre‐chemotherapy AI and post‐chemotherapy AI was 0.84 in the OR group and 0.01 in the NR group , ( rho = 0.4 ; p = 0.006 ) . There was no change in Bcl‐2 protein expression following chemotherapy . In the OR group , p53 protein expression was positive in 41.6 % of patients before and in 22.2 % after chemotherapy ( difference = 16.6 % ; p = 0.03 ) . No change was detected in the NR group . Conclusion : A positive correlation was found between the increase in AI and clinical response to neoadjuvant chemotherapy in locally advanced breast cancer Abstract Purpose . Primary chemotherapy is commonly used in patients with breast cancer to downstage the primary tumour prior to surgery . There is a need to establish , prior to commencement of chemotherapy , predictors of clinical and pathological response , which may then be surrogate markers for patient survival and thus allow identification of patients who are most likely to benefit from such treatment . Patients and methods . A total of 104 patients with large and locally advanced breast cancers received an anthracycline/docetaxel-based regimen prior to surgery . Immunohistochemistry was carried out on pre-treatment core biopsies of the tumour to detect hormone receptors ( oestrogen-ER ; progesterone-PR ) , a proliferation marker ( MIB-1 ) , the oncoprotein Bcl-2 , an extracellular matrix degradation enzyme ( cathepsin D ) , p53 , and an oestrogen associated protein ( pS2 ) . Both clinical and pathological response were assessed following completion of chemotherapy . Results . Patients whose tumours did not express oestrogen receptor ( p= 0.02 ) or did not express Bcl-2 ( p < 0.01 ) had a better pathological response in a univariate analysis . However , in a multivariate model , it was only the absence of detectable Bcl-2 protein that predicted a better pathological response ( p= 0.001 ) . Conclusions . This study has identified that patients whose breast cancers are most likely to experience the greatest degree of tumour destruction by primary chemotherapy do not express either oestrogen receptors or Bcl-2 . This may have important implication s in the selection of patients with breast cancer for primary chemotherapy who are most likely to gain a survival benefit TP53 status [ mutations , immunostaining , and loss of heterozygosity ( LOH ) ] , expression of c-erbB-2 , bcl-2 , and histological grading were correlated to the response to doxorubicin monotherapy ( 14 mg/m2 ) administered weekly to 90 patients with locally advanced breast cancer . Mutations in the TP53 gene , in particular those affecting or disrupting the loop domains L2 or L3 of the p53 protein , were associated with lack of response to chemotherapy ( P = 0.063 for all mutations and P = 0.008 for mutations affecting L2/L3 , respectively ) . Similarly , expression of c-erbB-2 ( P = 0.041 ) , a high histological grade ( P = 0.023 ) , and lack of expression of bcl-2 ( P = 0.018 ) all predicted chemoresistance . No statistically significant association between either p53 immunostaining or TP53 LOH and response to therapy was recorded , despite the finding that both were associated with TP53 mutation status ( p53 immunostaining , P < 0.001 ; LOH , P = 0.021 ) . Lack of immunostaining for p53 despite mutation of the TP53 gene was particularly seen in tumors harboring nonsense mutations or deletions/splices ( 7 of 10 negative for staining compared with 4 of 16 with missense mutations ) . TP53 mutations ( total/affecting L2/L3 domains ) were associated with expression of c-erbB-2 ( P < 0.001 for both ) , high histological grade ( P = 0.001 and P = 0.025 ) , and bcl-2 negativity ( P = 0.003 and P = 0.002 ) . TP53 mutations , histological grade , and expression of bcl-2 ( but not LOH or c-erbB-2 expression ) all predicted for relapse-free as well as breast cancer-specific survival in univariate analysis ( Ps between < 0.0001 and 0.0155 ) , but only tumor grade was found to be predictive in multivariate analysis ( P = 0.01 and P = 0.0007 , respectively ) . Our data are consistent with the hypothesis that certain TP53 mutations predict for resistance to doxorubicin in breast cancer patients . However , the observation that the majority of patients with TP53 mutations affecting or disrupting the L2/L3 domains with LOH in addition ( n = 12 ) obtained a partial response ( n = 4 ) or stabilization of disease ( n = 5 ) during chemotherapy suggests redundant mechanisms to compensate for loss of p53 function . Our findings are consistent with the hypothesis that other defects may act in concert with loss of p53 function , causing resistance to doxorubicin in breast cancers PURPOSE BCL2 overexpression is a hallmark of chronic lymphocytic leukemia ( CLL ) . The novel BH3 mimetic navitoclax ( ABT-263 ) specifically inhibits BCL2 and related proteins BCL-x(l ) and BCL-w , potently inducing apoptosis of CLL cells in vitro . A phase I trial in patients with CLL was conducted to evaluate the safety , pharmacokinetics , and biologic activity of oral navitoclax . PATIENTS AND METHODS Twenty-nine patients with relapsed or refractory CLL received daily navitoclax for 14 days ( 10 , 110 , 200 , or 250 mg/d ; n = 15 ) or 21 days ( 125 , 200 , 250 , or 300 mg/d ; n = 14 ) of each 21-day cycle . Dose escalation decisions were informed by continual re assessment methodology . RESULTS Lymphocytosis was reduced by more than 50 % in 19 of 21 patients with baseline lymphocytosis . Among 26 patients treated with navitoclax ≥ 110 mg/d , nine ( 35 % ) achieved a partial response and seven maintained stable disease for more than 6 months . Median treatment duration was 7 months ( range , 1 to ≥ 29 months ) . Median progression-free survival was 25 months . Activity was observed in patients with fludarabine-refractory disease , bulky adenopathy , and del(17p ) CLL . Thrombocytopenia due to BCL-x(l ) inhibition was the major dose-limiting toxicity and was dose-related . Low MCL1 expression and high BIM : MCL1 or BIM : BCL2 ratios in leukemic cells correlated with response . We determined that the navitoclax dose of 250 mg/d in a continuous dosing schedule was optimal for phase II studies . CONCLUSION BCL2 is a valid therapeutic target in CLL , and its inhibition by navitoclax warrants further evaluation as monotherapy and in combination in this disease The aim of this study was to evaluate preoperative tumour expression of NAD(P)H : quinone oxidoreductase 1 ( NQO1 ) along with other biological markers as potential predictors of pathological complete response ( pCR ) to neoadjuvant docetaxel , doxorubicin , and cyclophosphamide-containing ( TAC ) chemotherapy in patients with primary breast cancer . Sixty-one patients who received neoadjuvant chemotherapy ( NCT ) with TAC regimen were enrolled in this prospect i ve study . The pre- and post- NCT expression of oestrogen receptor ( ER ) , progesterone receptor ( PR ) , epidermal growth factor receptor 1 and 2 ( EGFR and HER2 ) , NQO1 , Ki-67 proliferation index , multidrug resistance protein 1 ( MDR1 ) , p53 and BCL2 were evaluated by immunohistochemistry . The pCR was reached in 14 patients ( 23 % of the study group ) . Multivariate analysis demonstrated that patients with ER- , PR- , NQO1- negative , and Ki-67-positive tumours had a significantly higher chance to achieve pCR . Within the biological subtypes , the highest pCR rate ( 50 % ) was seen in triple-negative ( i.e. ER- , PR- , HER2- ) tumours . Post-operative evaluation showed that in comparison to pre-operative tissue sample s , NQO1 expression was significantly increased , while Ki-67 and HER2 decreased , in the residual tissue after NCT . In conclusion , the present data suggests that NQO1 expression may be a novel diagnostic biomarker for the prediction of positive response to NCT in patients with breast cancer BACKGROUND Proteins of the BCL-2 family regulate clonal selection and survival of lymphocytes , and are frequently overexpressed in lymphomas . Navitoclax is a targeted high-affinity small molecule that inhibits the anti-apoptotic activity of BCL-2 and BCL-XL . We aim ed to assess the safety and antitumour activity of navitoclax in patients with lymphoid tumours , and establish the drug 's pharmacokinetic and pharmacodynamic profiles . METHODS In this phase 1 dose-escalation study , patients ( aged ≥18 years ) with relapsed or refractory lymphoid malignancies were enrolled and treated at seven sites in the USA between November , 2006 , and November , 2009 . A modified Fibonacci 3 + 3 design was used to assign patients to receive oral navitoclax once daily by one of two dosing schedules : intermittently for the first 14 days of a 21-day cycle ( 14/21 ) at doses of 10 , 20 , 40 , 80 , 110 , 160 , 225 , 315 , or 440 mg/day ; or continuously for 21 days of a 21-day cycle ( 21/21 ) at doses of 200 , 275 , 325 , or 425 mg/day . Study endpoints were safety , maximum tolerated dose , pharmacokinetic profile , pharmacodynamic effects on platelets and T cells , and antitumour activity . This trial is registered with Clinical Trials.gov , number NCT00406809 . FINDINGS 55 patients were enrolled ( median age 59 years , IQR 51 - 67 ) , 38 to receive the 14/21 dosing schedule , and 17 to receive the 21/21 dosing schedule . Common toxic effects included grade 1 or 2 anaemia ( 41 patients ) , infection ( 39 ) , diarrhoea ( 31 ) , nausea ( 29 ) , and fatigue ( 21 ) ; and grade 3 or 4 thrombocytopenia ( 29 ) , lymphocytopenia ( 18 ) , and neutropenia ( 18 ) . On the intermittent 14/21 schedule , dose-limiting toxic effects were hospital admissions for bronchitis ( one ) and pleural effusion ( one ) , grade 3 increase in aminotransferases ( one ) , grade 4 thrombocytopenia ( one ) , and grade 3 cardiac arrhythmia ( one ) . To reduce platelet nadir associated with intermittent 14/21 dosing , we assessed a 150 mg/day lead-in dose followed by a continuous 21/21 dosing schedule . On the 21/21 dosing schedule , two patients did not complete the first cycle and were excluded from assessment of dose-limiting toxic effects ; dose-limiting toxic effects were grade 4 thrombocytopenia ( one ) , grade 3 increase in aminotransferases ( one ) , and grade 3 gastrointestinal bleeding ( one ) . Navitoclax showed a pharmacodynamic effect on circulating platelets and T cells . Clinical responses occurred across the range of doses and in several tumour types . Ten of 46 patients with assessable disease had a partial response , and these responders had median progression-free survival of 455 days ( IQR 40 - 218 ) . INTERPRETATION Navitoclax has a novel mechanism of peripheral thrombocytopenia and T-cell lymphopenia , attributable to high-affinity inhibition of BCL-XL and BCL-2 , respectively . On the basis of these findings , a 150 mg 7-day lead-in dose followed by a 325 mg dose administered on a continuous 21/21 dosing schedule was selected for phase 2 study . FUNDING Abbott Laboratories , Genentech , and National Cancer Institute , National Institutes of Health OBJECTIVE To identify the predictive markers associated with chemotherapy sensitivity , especially those producing pathological complete response ( pCR ) following neoadjuvant chemotherapy ( NACT ) in patients with locally advanced breast cancer . METHODS Core needle biopsy of 50 locally advanced breast cancer patients was analysed for histopathology , grade , oestrogen receptor , progesterone receptor , HER2 , Ki-67 , p53 , Bcl-2 , and BAX before starting NACT . This was correlated with response to NACT using Response Evaluation Criteria in Solid Tumours criteria . RESULTS The mean tumour reduction rate per chemotherapy cycle was significantly higher in BAX-positive ( p = 0.01 ) and Bcl-2-negative ( p = 0.04 ) tumours . BAX expression significantly ( p = 0.043 ) correlated with a response of an at least 30 % reduction in tumour size post-NACT on multivariate analysis . A significant relationship was seen between loss of Bcl-2 expression and pCR on univariate ( p = 0.048 ) analysis . Overall , all of the above 12 parameters had 30.4 % and 28.5 % success in predicting clinical complete response and pCR , respectively , by the Cox and Snell formula . CONCLUSION Of all parameters examined , only the apoptosis-related genes ( Bcl-2 and BAX ) seemed to exert some influence on the response to NACT , and neither by itself was sufficient to predict pCR ; however , 50 patients is not sufficient to simultaneously analyse several predictive markers |
13,831 | 27,538,777 | Globally , we identified uncertainty with regard to the association of the evaluated biomarkers with stroke outcome , with little added value on top of clinical predictors such as age or stroke severity , which makes its implementation unlikely in clinical practice for global outcome prediction . | Stroke represents one of the most important causes of disability and death in developed countries .
However , there is a lack of prognostic tools in clinical practice to monitor the neurological condition and predict the final outcome .
Blood biomarkers have been proposed and studied in this indication ; however , no biomarker is currently used in clinical practice .
The stroke-related neuroinflammatory processes have been associated with a poor outcome in stroke , as well as with poststroke complications .
In this review , we focus on the most studied blood biomarkers of this inflammatory processes , cytokines , and C-reactive protein , evaluating its association with outcome and complications in stroke through the literature , and performing a systematic review on the association of C-reactive protein and functional outcome after stroke . | Objectives : The cytokine interleukin (IL)-1 mediates ischaemic brain damage in rodents . The endogenous , highly selective , IL-1 receptor antagonist ( IL-1ra ) protects against ischaemic cerebral injury in a range of experimental setting s , and IL-1ra causes a marked reduction of cell death when administered peripherally or at a delay in transient cerebral ischaemia . We report here the first r and omised , double blind , placebo controlled trial of recombinant human IL-1ra ( rhIL-1ra ) in patients with acute stroke . Methods : Patients within 6 hours of the onset of symptoms of acute stroke were r and omised to rhIL-1ra or matching placebo . Test treatment was administered intravenously by a 100 mg loading dose over 60 seconds , followed by a 2 mg/kg/h infusion over 72 h. Adverse events and serious adverse events were recorded for up to 3 months , serial blood sample s were collected for biological markers up to 3 months , and 5–7 day brain infa rct volume was measured by computed tomography . Results : No adverse events were attributed to study treatment among 34 patients r and omised . Markers of biological activity , including neutrophil and total white cell counts , C reactive protein , and IL-6 concentrations , were lower in rhIL-1ra treated patients . Among patients with cortical infa rcts , clinical outcomes at 3 months in the rhIL-1ra treated group were better than in placebo treated . Conclusions : These data suggest that rhIL-1ra is safe and well tolerated in acute stroke . In addition , rhIL-1ra exhibited biological activity that is relevant to the pathophysiology and clinical outcome of ischaemic stroke . Our findings identify rhIL-1ra as a potential new therapeutic agent for acute stroke Background and Purpose . Inflammation exists in inception , progression , and reperfusion of acute ischemic stroke . Insightful underst and ing of correlation in inflammatory mediators and stroke severity with intracranial artery stenosis may improve rational stroke therapy . Methods . We prospect ively recruited 977 patients with acute noncardioembolic ischemic stroke with MCA stenosis by MRA as none to mild ( < 50 % ) , moderate ( 50–69 % ) , severe ( 70–99 % ) , or occlusive ( 100 % ) . The peripheral levels of WBC , homocysteine ( HCY ) , and high sensitivity C-reactive protein ( hs-CRP ) were recorded . All patients were assessed of 1-year outcome by mRS as favorable ( 0–2 ) or poor ( 3–6 ) . Results . The levels of WBC , HCY , and hs-CRP had no significant differences in patients with categorized MCA stenosis ( all P > 0.05 ) . Higher levels of WBC , HCY , and hs-CRP were found in patients with 1-year poor outcome ( all P < 0.05 ) , but only hs-CRP is an independent predictor ( OR 1.06 , 95 % CI 1.027–1.093 , P = 0.0003 ) . The combination of any two of increased hs-CRP ( > 3 mg/L ) , WBC ( > 6.91 × 109/L ) , and HCY ( > 15 μmol/L ) had higher power in predicting 1-year poor outcome than the single elevated mediator . Conclusions . Elevated hs-CRP independently predicts 1-year poor outcome in acute stroke . The combination of increased hs-CRP , WBC , or HCY had a stronger predictive value in poor outcome than individual elevated mediator BACKGROUND Statins reportedly have anti-inflammatory effects aside from their cholesterol-lowering effect . We investigated the effects of statins on serum hs-CRP level and clinical outcome of acute ischemic stroke ( IS ) patients . METHODS This prospect i ve cohort study consequently evaluated patients with acute IS in a single medical center . Serum hs-CRP levels were measured at different time points ( within 48 h and 30 days post-stroke ) . The patients ' clinical and laboratory data on admission were analyzed . RESULTS Total 100 patients with acute IS were divided in the statin group ( n=50 ) and the non-statin group ( n=50 ) . Serum hs-CRP level was similar in the 2 groups within 48 h after acute IS , but was significantly lower in the statin group on Day 30 compared to the non-statin group ( p<0.05 ) . The statin group also had favorable 3-month outcome compared to the non-statin group ( p<0.05 ) . After adjustments for covariance using stepwise logistic regression , only NIHSS on admission ( OR=1.38 , 95 % CI=1.06 - 1.80 ; p=0.02 ) and hs-CRP in the acute phase ( OR=1.74 , 95 % CI=1.30 - 2.33 ; p=0.001 ) were significantly and independently predictive of 3-month outcome . CONCLUSION Statin therapy reduces serum hs-CRP level and may be associated with favorable 3-month outcome in patients after acute IS Background Inflammation is known to worsen cerebral damage at the acute phase of stroke . In this setting , cell adhesion molecules ( CAMs ) play a crucial role mediating migration of immune cells into the infa rct ed area . However , their value in long-term outcome prediction for patients with cerebrovascular diseases ( CVD ) is less described . Methods Levels of four CAMs ( E-selectin , P-selectin glycoprotein lig and -1 , intercellular adhesion molecule-1 , and vascular cell adhesion molecule-1 ( VCAM-1 ) ) and six other known biomarkers ( C-reactive protein ( CRP ) , interleukin-6 ( IL-6 ) , N-terminal pro-brain natriuretic peptide ( NT-proBNP ) , troponin I , vasopressin-neurophysin 2-copeptin , and S100 calcium-binding protein B ) were measured in a population of patients presenting CVD . Blood collection s for analysis were performed within different time windows after stroke onset : 0–6 h , 6–36 h , 2–3 days , 5–7 days , and 2–3 weeks . Independent associations with poor outcome at 3 months ( modified Rankin Scale score > 2 ) were sought using univariate and multivariate analysis after adjustments for age and National Institute of Health Stroke Scale score . Predictive ability of each biomarker has also been assessed with ROC analysis . Results One hundred patients were prospect ively included whom 75 presented with ischemic strokes , nine with hemorrhagic strokes and 16 with transient ischemic attacks . During the first 6 h after stroke onset , E-selectin was found to be an independent predictor of 3-month outcome ( odds ratio ( OR ) = 24 ; 95 % confidence interval ( 95 % CI ) , 2–354 ; p = 0.022 ) ( area under the curve ( AUC ) = 78 % ) , as was VCAM-1 during the third week after onset ( OR = 8 ; 95 % CI , 2–37 ; p = 0.01 ) ( AUC = 73 % ) . Associations remained after the exclusion of patients with hemorrhagic strokes and transient ischemic attacks . Independent associations with outcome were also found for CRP ( OR = 5 ; 95 % CI , 1–22 ; p = 0.023 ) and IL-6 ( OR = 5 ; 95 % CI , 1–17 ; p = 0.021 ) at 2–3 days and for NT-proBNP at 6–36 h ( OR = 20 ; 95 % CI , 1–337 ; p = 0.04 ) . Conclusions E-selectin and VCAM-1 were independent predictors of outcome in a population of patients with CVD . The predictive capability of other biomarkers known to be indicators for prognosis also emerged , confirming the study ’s robustness . CAMs levels could be considered as objective biological criteria for prognosis in CVD Background and Purpose — There is growing evidence of the prognostic importance of C-reactive protein ( CRP ) in ischemic stroke . However , the independent value of CRP at different stages after stroke has not been established . Therefore , we assessed the prognostic values of CRP in ischemic stroke . We also compared the relation of CRP at admission and discharge with 1-year outcome . Methods — One hundred ninety-three patients were included in a derivation set ( n=128 ) and a validation set ( n=65 ) . Serum CRP was measured , within 24 hours after index ischemic stroke , within 48 to 72 hours , and at hospital discharge . We examined the association between the level of CRP at different stages after stroke and outcome . We adjusted for the possible confounding effect using a multivariate Cox proportional hazard model . Results — A cutoff point of 1.5 mg/dL for CRP at discharge provided optimum sensitivity and specificity for adverse outcome , based on the receiver operator curves . CRP at admission ( hazard ratio [ HR ] 2.78 , 95 % CI 1.45 to 5.33;P = 0.0021 ) and discharge ( HR 9.42 , 95 % CI 4.27 to 19.05;P < 0.0001 ) were predictors of the combined end point of new vascular events or death at 1 year . CRP at hospital discharge was the strongest independent marker of adverse outcome ( HR 7.42 , 95 % CI 2.75 to 20.03;P = 0.0001 ) . These results were confirmed in the validation set ( HR 15.66 , 95 % CI 3.36 to 72.97;P = 0.0005 ) . Conclusions — CRP is a marker of increased 1-year risk in ischemic stroke . CRP at discharge is better related to later outcome and could be of greater utility for risk stratification . These findings are consistent with the hypothesis that elevated CRP may predict future cardiovascular events or death Background Cerebral ischaemia initiates an inflammatory response in the brain and periphery . We assessed the relationship between peak values of plasma interleukin-6 ( IL-6 ) in the first week after ischaemic stroke , with measures of stroke severity and outcome . Methods Thirty-seven patients with ischaemic stroke were prospect ively recruited . Plasma IL-6 , and other markers of peripheral inflammation , were measured at pre-determined timepoints in the first week after stroke onset . Primary analyses were the association between peak plasma IL-6 concentration with both modified Rankin score ( mRS ) at 3 months and computed tomography ( CT ) brain infa rct volume . Results Peak plasma IL-6 concentration correlated significantly ( p < 0.001 ) with CT brain infa rct volume ( r = 0.75 ) and mRS at 3 months ( r = 0.72 ) . It correlated similarly with clinical outcome at 12 months or stroke severity . Strong associations were also noted between either peak plasma C-reactive protein ( CRP ) concentration or white blood cell ( WBC ) count , and all outcome measures . Conclusions These data provide evidence that the magnitude of the peripheral inflammatory response is related to the severity of acute ischaemic stroke , and clinical outcome Inflammatory markers have been associated with functional outcome and mortality of stroke . We investigated the changes in procalcitonin ( PCT ) and high-sensitivity C-reactive protein ( Hs-CRP ) levels during the acute period of ischemic stroke and evaluated the relationship between these levels and the long-term functional outcome and mortality . We prospect ively studied 376 patients with acute ischemic stroke ( AIS ) who were admitted within 24 h after the onset of symptoms . PCT , Hs-CRP , and NIH Stroke Scale ( NIHSS ) were measured at the time of admission . Long-term functional outcome were measured by modified Rankin scale ( mRS ) at 1 year after admission . The correlations between the levels of PCT , Hs-CRP , and mortality at 1 year after stroke onset were analyzed . Patients with poor with functional outcome and non-survivors had significantly increased PCT and Hs-CRP levels on admission . Multivariate logistic regression analysis showed that PCT was an independent prognostic marker of 1-year functional outcome and death [ odds ratio ( OR ) 2.33 ( 95 % CI , 1.33–3.44 ) and 3.11 ( 2.02–4.43 ) , respectively , P < 0.0001 for both , adjusted for age , NIHSS , other predictors , and vascular risk factors ] in patients with AIS . The area under the receiver operating characteristic curve of PCT was 0.77 ( 95 % CI , 0.72–0.83 ) for functional outcome and 0.88 ( 95 % CI , 0.84–0.93 ) for mortality . PCT improved the area under the receiver operating characteristic curve of the NIHSS score for functional outcome from 0.74 ( 95 % CI , 0.66–0.81 ) to 0.85 ( 95 % CI , 0.76–0.92 ; P < 0.0001 ) and for mortality from 0.77 ( 95 % CI , 0.70–0.83 ) to 0.94 ( 95 % CI , 0.89–0.97 ; P < 0.0001 ) . Serum level of PCT at admission was an independent predictor of long-term functional outcome and mortality after ischemic stroke in Chinese sample Background and Purpose — The prediction of death or disability ( “ poor outcome ” ) after stroke by vali date d clinical models might be improved by the addition of blood biomarker measurements . We investigated whether such measurements improved the classification of patients into 4 categories of predicted risk of poor outcome : very high , intermediate high , intermediate low , and very low . Methods — We prospect ively recruited symptomatic patients within 24 hours of ischemic cerebrovascular events . We measured clinical prognostic variables in each patient . We drew blood soon after admission and measured markers of inflammation , thrombosis , cardiac strain , and cerebral damage . We assessed poor outcome at 3 months with the modified Rankin Scale and recovery of symptoms at 24 hours . We measured the association between blood marker levels and poor outcome after adjustment for stroke severity and age with multivariate logistic regression . Where these associations were statistically significant , we calculated the net reclassification index . Results — We recruited 270 patients with acute ischemic cerebrovascular events . At 3 months , 112 patients had a poor outcome . After adjustment for stroke severity and age , only interleukin-6 and N-terminal pro-brain natriuretic peptide were significantly associated with poor outcome . The addition of either interleukin-6 or N-terminal pro-brain natriuretic peptide to National Institutes of Health Stroke Scale and age did not improve the prediction of a poor outcome . Conclusions — Neither interleukin-6 nor N-terminal pro-brain natriuretic peptide had sufficient predictive power to be of clinical use to predict poor outcome after stroke . The search for better markers to improve the classification of patients across clinical ly relevant boundaries of predicted probabilities of outcome events needs to continue Background Clinical -Diffusion mismatch ( CDM ; NIHSS score ≥8 & DWI lesion volume ≤25 mL ) and Perfusion-Diffusion mismatch ( PDM ; difference > 20 % between initial DWI and MTT lesion volumes ) have been proposed as surrogates for ischemic brains that are at risk of infa rct ion . However , their utility to improve the selection of patients for thrombolytic treatment remains controversial . Our aim was to identify molecular biomarkers that can be used with neuroimaging to facilitate the selection of ischemic stroke patients for systemic thrombolysis . Methods We prospect ively studied 595 patients with ischemic stroke within 12 h of the stroke onset . A total of 184 patients received thrombolytic treatment according to the SITS-MOST criteria . DWI and MTT volumes were measured at admission . The main outcome variable was good functional outcome at 3 months ( modified Rankin scale < 3 ) . Serum levels of glutamate ( Glu ) , IL-10 , TNF-α , IL-6 , NSE , and active MMP-9 also were determined at admission . Results Patients treated with t-PA who presented with PDM had higher IL-10 levels at admission ( p < 0.0001 ) . In contrast , patients with CDM had higher levels of IL-10 ( p < 0.0001 ) as well as Glu and TNF-α ( all p < 0.05 ) and lower levels of NSE and active MMP-9 ( all p < 0.0001 ) . IL-10 ≥ 30 pg/mL predicts good functional outcome at 3 months with a specificity of 88 % and a sensitibity of 86 % . IL-10 levels ≥30 pg/mL independently in both patients with PDM ( OR , 18.9 ) and CDM ( OR , 7.5 ) , after an adjustment for covariates . Conclusions Serum levels of IL-10 facilitate the selection of ischemic stroke patients with CDM and PDM for systemic thrombolysis Background and Purpose The mechanisms for clinical deterioration in patients with ischemic stroke are not completely understood . Several proinflammatory cytokines are released early after the onset of brain ischemia , but it is unknown whether inflammation predisposes to neurological deterioration . We assessed the implication of interleukin (IL)-6 and tumor necrosis factor (TNF)-&agr ; in early neurological worsening in ischemic stroke . Methods Two hundred thirty-one patients consecutively admitted with first-ever ischemic cerebral infa rct ion within the first 24 hours from onset were included . Neurological worsening was defined when the Canadian Stroke Scale ( CSS ) score fell at least 1 point during the first 48 hours after admission . IL-6 and TNF-&agr ; were determined in plasma and cerebrospinal fluid ( CSF ; n=81 ) obtained on admission . Results Eighty-three patients ( 35.9 % ) deteriorated within the first 48 hours . IL-6 in plasma ( > 21.5 pg/mL ; OR 37.7 , CI 11.9 to 118.8 ) or in CSF ( > 6.3 pg/mL ; OR 13.1 , CI 2.2 to 77.3 ) were independent factors for early clinical worsening , with multiple logistic regression . The association was statistically significant in all ischemic stroke subtypes as well as in subjects with cortical or subcortical infa rct ions . IL-6 in plasma was highly correlated with body temperature , glucose , fibrinogen , and infa rct volume . CSF and plasma concentrations of TNF-&agr ; were also higher in patients who deteriorated , but the differences observed did not remain significant on multivariate analysis . Conclusions In addition to participating in the acute-phase response that follows focal cerebral ischemia , IL-6 levels on admission are associated with early clinical deterioration . The association between IL-6 and early neurological worsening prevails without regard to the initial size , topography , or mechanism of the ischemic infa rct ion Background and Purpose — & agr;-Melanocyte stimulating hormone ( & agr;-MSH ) is an endogenously produced neuropeptide derived from the same precursor as adrenocorticotropic hormone . & agr;-MSH has profound immunomodulatory properties and may also be neuroprotective . Nothing is known about & agr;-MSH and changes in its plasma concentrations in patients with acute ischemic stroke . Methods — In this prospect i ve observational study , plasma concentrations of & agr;-MSH , adrenocorticotropic hormone , cortisol , and interleukin 6 were assessed longitudinally over the course of 1 year after stroke onset in 111 patients . Logistic regression was used to the effect of initial plasma & agr;-MSH , adrenocorticotropic hormone , cortisol , and interleukin 6 on long-term outcome . Results — There was an early decrease in plasma & agr;-MSH in patients with severe stroke ( National Institutes of Health Stroke Scale ≥17 ) that normalized over the course of the year ; these same patients evidence d elevations in plasma cortisol and interleukin 6 . Higher initial plasma & agr;-MSH , but not adrenocorticotropic hormone , cortisol , or interleukin 6 , was independently predictive of good long-term outcome . Conclusions — This research is the first to study endogenous changes in plasma & agr;-MSH after stroke . The independent effect of early plasma & agr;-MSH on stroke outcome , as well as a growing body of experimental data demonstrating improved stroke outcome with exogenous & agr;-MSH administration , suggests a potential therapeutic role for & agr;-MSH in the treatment of stroke Abstract Background : Ischemic stroke is one of the most common causes of death worldwide . Early and accurate prediction of outcome in acute ischemic stroke ( AIS ) is important and influences risk-optimized therapeutic strategies . We investigated the changes in high-sensitivity C-reactive protein ( Hs-CRP ) and homocysteine ( HCY ) levels , two of the risk factors , during the acute period of AIS and evaluated the relationship between these levels and short-term prognosis . Methods : We prospect ively studied 189 patients with AIS who were admitted within 24 hours after the onset of symptoms . Serum Hs-CRP , HCY levels , and National Institutes of Health Stroke Scale ( NIHSS ) were measured at the time of admission . Short-term functional outcome was measured by the modified Rankin scale ( mRS ) , 90 days after admission . Results : The median serum Hs-CRP and HCY levels were significantly higher in AIS patients as compared to normal controls ( P < 0·0001 , respectively ) . High-sensitivity C-reactive protein and HCY were independent prognostic markers of functional outcome and death ( adjusted for age and the NIHSS ) in patients with AIS . In receiver operating characteristic curve analysis , the prognostic accuracy of the combined model ( HCY and Hs-CRP ) was higher compared to all measured biomarkers individually and the NIHSS score . Conclusion : High-sensitivity C-reactive protein and HCY are independent predictors of short-term outcome and mortality after AIS . The combined model may provide additional general prognostic information BACKGROUND AND PURPOSE Serological evidence of infection with Chlamydia pneumoniae has been associated with cardiovascular disease in multiple epidemiological studies . The data on its association with ischemic stroke are limited . We sought to determine whether chronic C pneumoniae infection is associated with ischemic stroke in a multi-ethnic population . METHODS The Northern Manhattan Stroke Study contains a population -based , case-control study component . Cases had first ischemic stroke and matched control subjects were derived through r and om digit dialing . Titers of IgG , IgA , and IgM antibodies specific for C pneumoniae were measured with the use of microimmunofluorescence , and titers > /=1:16 were considered positive . Conditional logistic regression was used to calculate odds ratios ( ORs ) and 95 % confidence intervals ( 95 % CIs ) after adjustment for medical , behavioral , and socioeconomic factors . RESULTS Eighty-nine cases and 89 control subjects were selected . Mean age among cases was 68.5+/-12.8 years ; 53 % were women and 15 % of the subjects were white , 28 % were black , and 54 % were Hispanic . Elevated C pneumoniae IgA titers were significantly associated with risk of ischemic stroke after adjusting for other stroke risk factors ( adjusted OR 4 . 51 , 95 % CI 1.44 to 14.06 ) . IgG titers were less strongly associated with stroke risk ( adjusted OR 2.59 , 95 % CI 0.87 to 7.75 ) . The association of IgA with stroke risk was detected in both younger and older groups , in men and women , and in whites , blacks , and Hispanics . There was also a significant continuous increase in risk associated with the log-transformation of the titer for IgA ( adjusted OR 1.32 , 95 % CI 1.05 to 1.66 ) but not IgG. CONCLUSIONS Serological evidence of chronic infection with C pneumoniae is associated with risk of ischemic stroke in an urban , multi-ethnic population . IgA titers may be a better marker of this risk than are IgG titers . This association is independent of other vascular disease risk factors . Further prospect i ve epidemiological studies of the effect of this infection on stroke risk are warranted Background Ischemic stroke patients are prone to infection by stroke-induced immunodepression . We hypothesized that levels of lipopolysaccharide binding protein ( LBP ) , interleukin-10 ( IL-10 ) , IL-6 and C-reactive protein ( CRP ) are early predictors for the development of stroke-associated infection . Methods Fifty-six patients with ischemic stroke ( n = 51 ) and transient ischemic attack ( TIA ) ( n = 5 ) who presented within 6 hours after symptom onset and who were free of detectable infection on admission were included in the study . Of these , 20 developed early infections during the first week . Blood sample s were taken at 6 , 12 , and 24 hours and at 3 and 7 days after stroke onset . Levels of LBP , Il-10 , IL-6 and CRP , as well as S100B , were measured as markers of inflammation and brain damage by commercially available immunometric tests . Results In the univariate analysis , levels of LBP , IL-10 , IL-6 and CRP significantly differed between patients who developed an infection and those who did not . In the binary logistic regression analysis , which was adjusted for National Institutes of Health Stroke Scale ( NIHSS ) on admission , stroke subtype and S100B peak levels , as indicator of the extent of brain damage , IL-10 at 6 hours , CRP at 6 hours and NIHSS on admission were identified as independent predictors of infection ( IL-10 : P = 0.009 ; CRP : P = 0.018 ; NIHSS : P = 0.041 ) . The area under the curve ( AUC ) of the receiver operating characteristic ( ROC ) curves in relation to the dichotomized status of the infection ( infection versus no infection ) was 0.74 ( 95 % confidence interval : 0.59 to 0.88 ) for CRP at 6 hours , 0.76 ( 0.61 to 0.9 ) for IL-10 at 6 hours , 0.83 ( 0.71 to 0.94 ) for NIHSS on admission and 0.94 ( 0.88 to 1 ) for the combination of CRP , IL-10 and NIHSS . In a sub analysis , 16 patients with early infections were matched with 16 patients without infection according to S100B peak levels . Here , the temporal pattern of LBP , IL-10 , IL-6 and CRP significantly differed between the patient groups . Conclusions Our data show that blood levels of inflammation markers may be used as early predictors of stroke-associated infection . We propose prospect i ve studies to investigate if the calculated cut-offs of CRP , IL-10 and NIHSS might help to identify patients who should receive early preventive antibiotic treatment Background and Purpose — Space-occupying brain edema is a life-threatening complication in patients with large hemispheric stroke . The aim of the study was to determine whether molecular markers of endothelial damage may help to predict secondary brain edema and , secondly , to identify patients who could benefit from aggressive therapies such as decompressive hemicraniectomy or hypothermia . Methods — We studied 40 consecutive patients with malignant middle cerebral artery ( MCA ) infa rct ion and 35 controls with massive MCA infa rct ions < 70 years of age and matched by stroke severity on admission . Cranial computed tomography ( CT ) was performed at entry and repeated between days 4 and 7 , or earlier if there was neurological worsening . Malignant MCA ( m-MCA ) infa rct ion was diagnosed when follow-up CT detected a more than two-thirds space-occupying MCA infa rct ion with midline shift , compression of the basal cisterns , and neurological deterioration . Plasma concentrations of glutamate , glycine , γ-aminobutyric acid , interleukin-6 ( IL-6 ) , IL-10 , tumor necrosis factor-α , matrix metalloproteinase-9 ( MMP-9 ) , and cellular-fibronectin ( c-Fn ) were determined in blood sample s obtained at admission . Results — Mean time from stroke onset to blood sampling was 6.3±4.8 in m-MCA and 7.7±6.0 hours in the control group ( P=0.63 ) . Baseline characteristics were comparable in both groups . c-Fn and MMP-9 levels were significantly higher in patients with m-MCA than in controls ( all P<0.001 ) . c-Fn > 16.6 & mgr;g/mL had the highest sensitivity ( 90 % ) , specificity ( 100 % ) , and negative and positive predictive values ( 89 % and 100 % , respectively ) for the prediction of m-MCA infa rct ion . Conclusions — A plasma c-Fn concentration > 16.6 & mgr;g/mL at admission is associated with the development of m-MCA infa rct ion with high sensitivity and specificity , suggesting that c-Fn might be useful in therapeutic decision making Background . The activation of inflammatory cascades triggered by ischemic stroke may play a key role in the development of infections . Methods . Patients admitted with ischemic stroke within 24 hours were prospect ively enrolled . Biomarkers of infection were measured on days 1 , 3 , and 5 . The patients were continuously monitored for predefined infections . Results . Patients with infection were older ( OR 1.06 per year , 95 % CI 1.01–1.11 ) and had a higher National Institute of Health Stroke Scale Score ( NIHSS , OR 1.21 , 95 % CI 1.10–1.34 ) , localization in the insula , and higher stroke volumes on diffusion-weighted imaging . The maximum temperature on days 1 and 3 , leukocytes , interleukin-6 , lipopolysaccharide-binding protein on days 1 , 3 , and 5 , C-reactive protein on days 3 and 5 , and procalcitonin on day 5 were higher and HLA-DR-expression on monocytes on days 1 , 3 , and 5 lower in patients with infection . Age and NIHSS predicted the development of infections . Infection was an independent predictor of poor functional outcome . Conclusions . Severe stroke and increasing age were shown to be early predictors for infections after stroke To determine whether serum procalcitonin ( PCT ) levels at admission were associated with short-term functional outcome after acute ischemic stroke ( AIS ) in a cohort Chinese sample . We prospect ively studied 378 patients with AIS who were admitted within 24 h after the onset of symptoms . PCT and NIH stroke scale ( NIHSS ) were measured at the time of admission . Short-term functional outcome was measured by modified Rankin scale ( mRS ) 90 days after admission . The results indicated that the serum PCT levels were significantly higher in AIS patients as compared to normal controls ( P < 0.0001 ) . In the 114 patients with an unfavorable functional outcome , serum PCT levels were higher compared with those in patients with a favorable outcome ( 2.40 ( IQR , 1.10–3.69 ) ng/mL and 0.42 ( IQR , 0.10–1.05 ) ng/mL , respectively , P < 0.001 ) . PCT was an independent prognostic marker of functional outcome [ odds ratio ( OR ) 3.45 ( 2.29–4.77 ) , adjusted for the NIHSS and other possible confounders ] in patients with ischemic stroke , added significant additional predictive value to the clinical NIHSS score . In receiver operating characteristic curve analysis , the prognostic accuracy of PCT was higher compared to Hs-CRP and NIHSS score . PCT is an independent predictor of short-term functional outcome after ischemic stroke in Chinese sample even after correcting for possible confounding factors Background : The relationship between biochemical aspirin resistance ( AR ) and functional outcome of acute ischemic stroke is uncertain . Methods : Prospect ively , 269 patients with acute ischemic stroke were recruited . Their responsiveness to aspirin was evaluated by platelet function analyzer ( PFA‐100 ) . All patients received blood tests for fibrinogen , high‐sensitivity C‐reactive protein ( hs‐CRP ) , CD40‐lig and , P‐selectin , intercellular adhesion molecule ‐1 , von Willebr and factor ( vWF ) , and D – dimer . The patients ' National Institutes of Health Stroke Scale and modified Rankin Scale scores were recorded on admission , at 30 days , and at 90 days after stroke . Results : Closure‐time measured by PFA‐100 equipped with epinephrine/collagen cartridge ( Epi‐CT ) was < 193 seconds ( defined as AR ) in 83 patients ( 30.9 % ) . Patients with AR were less likely to have favorable outcome at 30 days ( 47.0 % , p = 0.047 ; odds ratio : 0.69 , 0.48–0.99 ) and 90 days ( 57.8 % , p = 0.037 ; odds ratio : 0.69 , 0.47–0.97 ) after stroke compared with those of patients without AR ( 60.2 % and 71.0 % , respectively ) . The Epi‐CT correlated with closure‐time measured by adenosine diphosphate/collagen cartridge ( r = 0.241 , p < 0.001 ) , blood white cell count ( r = −0.125 , p = 0.041 ) , low density lipoprotein cholesterol ( r = 0.120 , p = 0.050 ) , hs‐CRP ( r = −0.150 , p = 0.015 ) , vWF ( r = −0.134 , p = 0.028 ) , and body mass index ( r = 0.143 , p = 0.019 ) . Multivariate logistic regression analysis showed that higher National Institutes of Health Stroke Scale at admission , atrial fibrillation , increased plasma levels of hs‐CRP , and D – dimer were independent predictors for unfavorable stroke outcome at 90 days . Conclusion : Aspirin resistance evaluated by PFA‐100 test was associated with unfavorable 90‐day outcome . However , AR determined by PFA‐100 dose not predict 90‐day functional outcome . The results of PFA‐100 testing represented a complex interaction between drug effect , inflammatory reaction , and prothrombotic activity Objective : C-reactive protein , a well known marker of inflammation is being investigated as a probable marker of predicting acute cardiovascular events and its severity . The aim of the present study was to assess the possible role of highly-sensitivity C-reactive protein ( hs-CRP ) in predicting short-term functional outcome of ischemic stroke . Methodology : A prospect i ve study was conducted on subjects admitted with first attack of confirmed ischemic stroke . It included 50 male and 52 female . Serum hs-CRP was measured in the 2nd ( CRP-D2 ) and 5th days ( CRP-D5 ) post-stroke . Modified Rankin scale ( MRS ) was measured in all subjects in the 2nd ( MRS-D2 ) , 5th days ( MRS-D5 ) and also 3 month ( MRS-M3 ) after stroke to assess the short-term functional outcome and mortality of subjects . Results : The mean age of the patients was 71.75±11.44 years . The mortality rate was 47.1 % in the third months after stroke . There was no significant correlation between CRP-D2 and MRS-M3 and also between CRP-D5 and MRS-M3 ( P>0.05 ) . However there was a significant association between high CRP-D2 ( CRP>3 ) and MRS-M3 and also between high CRP-D5 and MRS-M3 ( P<0.005 ) . Conclusion : This study showed that the value of CRP by itself could not predict the severity of short-term functional disability and it might not be useful as a clinical tool for predicting outcome Background Neuroserpin has shown neuroprotective effects in animal models of cerebral ischemia and has been associated with functional outcome after ischemic stroke . Our aim was to study whether neuroserpin serum levels could be associated to biomarkers of excitotoxicity , inflammation and blood brain barrier disruption . Methods We prospect ively included 129 patients with ischemic stroke ( 58.1 % male ; mean age , 72.4 ± 9.6 years ) not treated with tPA within 12 hours ( h ) of symptoms onset ( mean time , 4.7 ± 2.1 h ) . Poor functional outcome at 3 months was considered as a modified Rankin scale score > 2 . Serum levels of neuroserpin , Interleukin 6 ( IL-6 ) , Intercellular adhesion molecule-1 ( ICAM-1 ) , active Matrix metalloproteinase 9 ( MMP-9 ) , and cellular fibronectin ( cFn ) ( determined by ELISA ) and glutamate ( determined by HPLC ) were measured on admission , 24 and 72 h. The main variable was considered the decrease of neuroserpin levels within the first 24 h. ROC analysis was used to select the best predictive value for neuroserpin to predict poor functional outcome due to a lack of linearity . Results The decrease of neuroserpin levels within the first 24 h was negatively correlated with serum levels at 24 hours of glutamate ( r = -0.642 ) , IL-6 ( r = -0.678 ) , ICAM-1 ( r = -0.345 ) , MMP-9 ( r = -0.554 ) and cFn ( r = -0.703 ) ( all P < 0.0001 ) . In the multivariate analysis , serum levels of glutamate ( OR , 1.04 ; CI95 % , 1.01 - 1.06 , p = 0.001 ) ; IL-6 ( OR , 1.4 ; CI95 % , 1.1 - 1.7 , p = 0.001 ) ; and cFn ( OR , 1.3 ; CI95 % , 1.1 - 1.6 , p = 0.002 ) were independently associated with a decrease of neuroserpin levels < 70 ng/mL at 24 h after adjusting for confounding factors . Conclusions These findings suggest that neuroprotective properties of neuroserpin may be related to the inhibition of excitotoxicity , inflammation , as well as blood brain barrier disruption that occur after acute ischemic stroke Background Chronic risk factors are well understood in cases of stroke as well as myocardial infa rct ion . Till date , several triggers for stroke are still under evaluation . Research ers have previously evaluated the relationship between preceding infection and inflammation and stroke onset . Purpose The purpose of study is to define the stroke triggers in a better way and to provide little more information for early intervention by controlling infections or other trigger factors Methods In this retrospective study , a st and ardized question naire was carried out to evaluate the signs , symptoms of preceding ( < 14 days ) infection , physical/mental health , drug history , TIA etc . of 70 ischemic stroke patients and 80 non-stroke out-patient department patients as control groups . Important biochemical tests e.g. high sensitivity CRP , leukocytes count , blood sugar , lipid profile , etc . were also taken into consideration . Recent ( 15 days ) prior infection , mainly respiratory tract infection and urinary tract infection , which were likely to be important stroke triggers , were compared between the ischemic stroke groups and the non-stroke patients ( control group ) . Results It was found that respiratory tract infection is the most common type of infection ( 48.5 % ) compared with the non-stroke control group ( 30 % ) . Apart from this , there were clinical evidence of infections like gastroenteritis , RTI , UTI etc which were biochemically established by leukocytosis and increased high-sensitivity C-Reactive Protein levels , well-known early diagnostic tools that have good predictive value . This study reveals that well-controlled diabetic , hypertensive or non-diabetic normotensive patients can suddenly develop ischemic stroke following recent infection as evidence d by clinical features , increased levels of high-sensitivity CRP and leukocytosis . Conclusion These diagnostic tools implicate the value of early treatment of febrile illness and introduction or adjustment of doses of antiplatelet agents , antibiotics , etc . to reduce the actual stroke incidence , though it needs multicentre large community based prospect i ve trials to evaluate stroke prone state and effective preventive measures tools at the same time BACKGROUND There is evidence of an association between mediators of inflammation , particularly C-reactive protein ( CRP ) , and outcome of acute ischaemic stroke . This provides a potential opportunity for interventions aim ed at improving outcome . There is sparse data exploring the role of inflammatory markers such as CRP and stroke outcome in Africans . The study objective was to determine the association between admission serum CRP levels and short-term outcome in the Nigerian patient presenting with acute ischaemic stroke . MATERIAL S AND METHODS Consecutive patients hospitalized for first-ever acute ischaemic stroke at the Lagos University Teaching Hospital , Lagos , Nigeria , were prospect ively enrolled between October 2007 and June 2008 . Stroke severity was assessed using the National Institutes of Health Stroke Scale ( NIHSS ) . Serum CRP was determined on sample s obtained within 7 days of stroke onset . All stroke patients were followed up till day 30 post-stroke . Outcome measures were 30 day Glasgow outcome scale score and functional impairment on the modified Rankin Scale ( mRS ) . An age- and gender-matched healthy control group had serum CRP determined at inclusion . Elevated CRP was defined as any level above the cutoff ( mean + 2 x st and ard deviation of CRP level of controls ) . RESULTS Eighty patients with acute ischaemic stroke ( 47 men and 33 women ) and 40 controls ( 27 male and 13 female ) ( P = 0.47 ) were studied . Mean age in cases was 59.1 ± 15.0 years . Mean CRP was significantly higher in stroke cases than controls ( 17.7 ± 14.4 mg/L versus 1.1 ± 1.7 mg/L respectively ) ( P < 0.00001 ) . The frequency of elevated CRP ( > 4.5 mg/L ) was 76.3 % in stroke ( N = 61 ) and 5 % ( N = 2 ) in controls ( P < 0.0001 ) . The case fatality rate in stroke with elevated CRP ( 32.8 % ) was significantly higher than stroke with normal admission CRP ( 0 % ; P = 0.015 ) . The association of higher admission CRP with fatality ( ) was statistically significant ( P < 0.0001 ) . Amongst survivors , mean CRP levels were markedly higher in the patients with unfavorable motor outcome ( moderate/severe disability ; n = 22 ; 21.5 ± 11.1 ) compared to those with favorable outcome ( mild disability ; n = 38 ; 6.5 ± 6.2 ) ( P < 0.00001 ) . In multivariate regression analysis , only high NIHSS score ( P = 0.004 ) and admission CRP ( P = 0.008 ) were independently associated with case fatality . CONCLUSIONS Elevated admission CRP and high NIHSS score are independent predictors of short-term case fatality and adverse functional outcome following acute ischaemic stroke in Nigerians Inflammatory reactions are involved in the pathogenesis of cerebral ischemia . Cytokines exacerbate brain ischemic injury by several mechanisms and they activate the synthesis of acute-phase reactants . We evaluated the association between cytokine-induced inflammation and functional outcome in 41 patients with acute ischemic stroke . Blood sample s for interleukin-1 receptor antagonist ( IL-1ra ) , erythrocyte sedimentation rate ( ESR ) , c-reactive protein ( CRP ) and polymorphonuclear leukocyte ( PMNL ) count were taken within 48 h from stroke onset . Functional outcome was assessed at six months with the Modified Rankin Scale . Patients with a Rankin score > or = 3 were classified as dependent outcome . The effect of inflammatory variables on outcome was analyzed by logistic regression . Mathew score < 75 on admission , atrial fibrillation , non-lacunar infa rct size , ESR>13 mm/h in men or > 20 mm/h in women , PMNL count > 8 x 10(9)/l , CRP>0.8 mg/dl and IL-1ra>500 pg/ml were associated with dependent outcome . On multiple logistic regression , severe stroke on admission , non-lacunar infa rct size and ESR remain in the predictive model of outcome with a sensitivity and specificity of 76 and 80 % , respectively . This study suggests that in addition to clinical evaluation and neuroimaging , measurement of ESR may be useful for the early detection of stroke patients with poor long-term functional outcome Objective Vascular disease recurrence following stroke is the main cause of morbidity and mortality . The MITICO study was design ed to assess the prognostic value of markers of inflammation in relation to the risk of recurrence of vascular disease . Patients and methods Multi-centered prospect i ve observational study , in patients with ischemic stroke not receiving anti-coagulation therapy and who were recruited within 1–3 months from stroke onset . Blood sample s were obtained at baseline and follow- up for the determination of high-sensitive C reactive protein ( CRP ) , IL-6 , IL-10 , ICAM-1 , VCAM- 1 , MMP-9 and cellular fibronectin . Four follow-up visits within the first year were to rule out recurrence . Results Of 965 patients from 65 hospitals , 780 ( aged 67.5±11.2 years , 33.6 % female ) were valid for main analysis . One-hundred and three patients ( 13.2 % ) had a new adverse vascular event and 116 patients ( 14.9 % ) a vascular event or vascular death ( 66.4 % stroke , 21.5 % coronary and 12.1 % peripheral ) . Levels of IL-6 > 5 pg/mL and VCAM-1 > 1350 ng/mL ( ROC curve analyses ) were associated with vascular disease recurrence risk ( OR : 28.7 ; 95 % CI : 14.2–58.0 vs. OR : 4.1 ; 95 % CI : 2.4–7.1 , respectively ) following adjustment for confounding variables . Risk of adverse vascular event or death from vascular disease were associated with IL-6 ( OR : 21.2 ; 95 % CI : 11.6–38.7 ) and VCAM-1 ( OR : 3.8 ; 95 % CI : 2.3–6.4 ) . Conclusions Baseline values of IL-6 > 5 pg/mL and VCAM-1 > 1350 ng/mL increase 21-fold and 4-fold , respectively , the risk of new vascular disease event or death from vascular disease in patients with ischemic stroke not receiving anti-coagulation treatment Experimental studies have recently suggested that acute ischemia may facilitate the appearance of fatal infections as part of a brain-induced immunodepression syndrome . However , the mechanisms and neurological consequences of infections complicating acute ischemic stroke have received much less attention at the bedside . The incidence of infection and death after non-septic stroke was compared in this prospect i ve study with longitudinal changes of cytokines , leukocytes , normetanephrine ( NMN ) and metanephrine ( MN ) in 75 consecutive patients . In multivariate analysis , infection , n = 13 ( 17 % ) , was associated with the upper quartile of MN ( OR 3.51 , 95 % CI 1.30 - 9.51 ) , neurological impairment ( NIHSS ) on admission ( OR 3.99 , 95 % CI 1.34 - 11.8 ) , monocyte count ( OR 1.78 , 95 % CI 1.13 - 2.79 ) , and increased interleukin (IL)-10 ( OR 1.54 , 95 % CI 1.00 - 2.38 ) . Mortality at 3 months , n = 16 ( 21 % ) , was associated with increased levels of NMN on admission ( OR 2.34 95 % CI 1.15 - 4.76 ) , NIHSS score ( OR 2.57 , 95 % CI 1.29 - 5.11 ) , and higher IL-6 levels ( OR 1.29 , 95 % 1.00 - 1.67 ) . These findings suggest that acute ischemic stroke is associated with an early activation of the sympathetic adrenomedullar pathway that lowers the threshold of infection and increases the risk of death . Moreover , these findings are independent of the blood borne effects of pro- and anti-inflammatory cytokines , and circulating leukocytes In a prospect i ve observational study , we assessed the relative value of conventional stroke risk factors and emerging markers in the prediction of functional outcome of patients surviving the acute phase of an ischemic non-embolic stroke . All available eligible patients consecutively admitted due to a first-ever acute ischemic non-embolic stroke during a 2-year period were evaluated . In a total of 105 patients ( 54 males , 51 diabetic ) a series of clinical , biochemical and imaging characteristics were recorded , including demographic data , blood pressure , serum glucose , insulin , lipids , inflammatory markers , intima-media thickness of the carotid arteries ( IMT ) , brain damage location and size of the infa rct volume . Barthel Activities of Daily Living Index ( BI ) scale was used to assess the severity of neurological deficit on admission and the functional outcome 6 months after discharge . Brain infa rct volume , stroke location in the anterior circulation , age , diabetes mellitus , IMT and plasma interleukin-1beta levels proved to be significant determinants of long-term functional outcome , assessed by BI disability score . ROC curve analyses indicated that the infa rct volume is superior to other predictors in the diagnosis of patients with unfavorable functional outcome ( BI<95 ) at 6 months post-discharge ( area under the curve , AUC=0.80 , 95 % confidence interval 0.64 - 0.95 ; p=0.003 ) . Significant differences in the mean infa rct volume were noted among age tertiles , with the diabetic patients in the 3rd tertile of age experiencing the worst outcome ( LSD test , p=0.019 ) . Taken together , the assessment of infa rct volume seems to have a significant predictive value regarding long-term functional outcome , especially in the elderly diabetic patients Background and Purpose — Recent studies described an association between elevated levels of C-reactive protein ( CRP ) and outcome after ischemic stroke . We investigated the impact of early serial CRP measurements in hyperacute ischemic stroke on long-term outcome . Methods — One hundred twenty-seven consecutive patients without thrombolysis with a first ischemic stroke no more than 12 hours after symptom onset were examined . Serial CRP measurements were done at admission ( CRP 1 ) , within 24 hours ( CRP 2 ) , and within 48 hours ( CRP 3 ) after symptom onset . In addition to several cerebrovascular risk factors , the 1-year outcome and the lesion volumes of initial diffusion-weighted images were determined . Results — The CRP concentration increased significantly during the first 48 hours after symptom onset ( CRP 1 , 0.86 mg/dL [ 95 % CI , 0.69 to 1.02 ] ; CRP 2 , 1.22 mg/dL [ 95 % CI , 0.88 to 1.55 ] ; CRP 3 , 1.75 mg/dL [ 95 % CI , 1.25 to 2.25];P = 0.003 ) . Multiple logistic regression analysis identified Barthel Index score at admission and CRP 2 and 3 as independent predictors of an unfavorable outcome . Kaplan-Meier analysis revealed a significantly higher rate of end point events ( adjusted odds ratio , 3.9 [ 95 % CI , 1.4 to 10.7];P = 0.008 ) only in patients with elevated CRP 2 concentrations . Conclusions — The CRP level measured within 12 hours after symptom onset of an acute ischemic stroke is not independently related to long-term prognosis . In contrast , a CRP increase between 12 and 24 hours after symptom onset predicts an unfavorable outcome and is associated with an increased incidence of cerebrovascular and cardiovascular events Objective To test the hypothesis that pre-treatment Creactive protein ( CRP ) predicts outcome in stroke patients undergoing intravenous thrombolysis ( IVT ) treatment . Methods We analyzed the data of 111 consecutive patients with IVT within 6 hours of stroke onset for stroke involving the middle cerebral artery territory and admission CRP ≤ 6 mg/dl . Results CRP levels were consistently , yet non-significantly lower in patients with unfavourable outcome definitions . Median ( range ) CRP levels were 0.3 ( 0–5.9 ) mg/dl vs. 0.4 ( 0–5.7 ) mg/dl ( p = 0.13 ) in patients dependent or dead after 3 months ( modified Rankin Scale score > 2 ; n = 59 ) vs. independent patients ( n = 52 ) ; 0.2 ( 0.1–1.5 ) mg/dl vs. 0.4 ( 0–5.9 ) mg/dl ( p = 0.28 ) in patients dead after 3 months ( n = 14 ) versus survivors ( n = 97 ) ; and 0.2 ( 0.1–0.7 ) mg/dl vs. 0.4 ( 0–5.9 ) mg/dl ( p = 0.09 ) in patients with significant neurological deterioration within 24 hours ( increase in ≥ 4 points on National Institute of Health Stroke scale ; n = 9 ) vs. patients without early deterioration ( n = 102 ) . Independent predictors of dependency/death after 3 months , identified by multivariate logistic regression analyses , were baseline NIHSS score ( OR = 1.31 , 95 % CI 1.16–1.48 , p < 0.001 ) , time from onset to treatment ( OR = 1.01 , 95 % CI 1.0–1.02 , p = 0.024 ) , and presence of diabetes ( OR = 8.16 , 95 % CI 1.18–56.5 , p = 0.033 ) . Conclusion Pre-treatment CRP clearly failed to predict outcome in stroke patients treated with IVT . Our findings contradict previously published work and highlight the need for further research on this topic Abstract Background : Inflammation may not only be the consequence of brain infa rct ion but it may also contribute to ischemic damage . However , the role of inflammatory markers in predicting functional outcome in stroke remains controversial . Objective : This study was conducted to evaluate the predictive value of admission high-sensitivity C-reactive protein ( hs-CRP ) and ferritin levels for functional disability in patients with acute ischemic stroke at 3-month follow-up and investigate the relationship between inflammatory markers and subtypes , severity , and risk factors of ischemic stroke . Methods : Sixty-two patients were examined prospect ively within 48 hours after onset of ischemic stroke . Plasma hs-CRP and ferritin measurements were obtained from patients within 48 hours after onset and at 3-month follow-up . Patients were divided into 2 groups based on the level of hs-CRP : elevated ( serum hs-CRP ≥0.5 mg/dL ) and normal ( serum hs-CRP<0.5 mg/dL ) hs-CRP groups . Stroke severity was analyzed by the National Institutes of Health Stroke Scale ( NIHSS ) and functional disability was assessed by the Functional Independence Measure ( FIM ) and Functional Ambulation Scale ( FAS ) . Stroke subtypes were classified according to the Oxfordshire Community Stroke Project . Results : Except for the correlation between hs-CRP levels and FIM scores on admission , no significant correlation was found between laboratory markers and FIM , FAS , and NIHSS scores and stroke subtypes on admission and at 3-month follow-up ( P > .05 ) . Conclusion : This study revealed that neither hs-CRP nor ferritin levels could predict functional disability 3 months after stroke onset . FIM , FAS , and NIHSS scores were more useful in predicting functional outcome 3 months after stroke onset than the laboratory markers evaluated in this study Although statins are being used for secondary prevention of ischemic stroke , recent experimental data have shown new pleiotropic effects of these drugs responsible for their role in neuroprotection . We conducted a pilot , double-blind , r and omized , multicenter clinical trial to study for the first time safety and efficacy of simvastatin in the acute phase of ischemic stroke . Simvastatin/placebo was given at 3 - 12 h from symptom onset to 60 patients with cortical strokes . Efficacy on the evolution of several inflammation markers [ interleukin (IL)-6 , IL-8 , IL-10 , monocyte chemoattractant protein-1 , intercellular adhesion molecule-1 , vascular cell adhesion molecule-1 , C-reactive protein , sApo/Fas , tumor necrosis factor-alpha , E-selectin , L-selectin and nitrites+nitrates ] and neurological outcome was evaluated at baseline , day 1 , 3 , 5 , 7 and 90 . No differences were found amongst the biomarkers studied regarding treatment allocation . Although simvastatin patients improved significantly by the third day ( 46.4 % vs. 17.9 % , P = 0.022 ) , a non-significant increase in mortality and greater proportion of infections ( odds ratio 2.4 , confidence interval 1.06 - 5.4 ) in the simvastatin group were the main safety concerns . Therefore , a larger clinical trial is needed to confirm the net benefit of this therapeutic approach Background and Purpose — We hypothesized that concentrations of interleukin 6 ( IL-6 ) , serum amyloid A , tumor necrosis factor-&agr ; receptor 1 , CD40 lig and , and monocyte chemoattractant protein 1 would predict recurrent ischemic stroke and major vascular events after recent lacunar stroke . Methods — Levels of Inflammatory Markers in the Treatment of Stroke ( LIMITS ) was an international , multicenter , prospect i ve ancillary biomarker study nested within the Secondary Prevention of Small Subcortical Strokes ( SPS3 ) study , a Phase III trial in patients with recent lacunar stroke . Crude and Adjusted Cox proportional hazards models were used to calculate hazard ratios ( HRs ) and 95 % confidence intervals ( 95 % CI ) for recurrence risks . Results — Among 1244 patients with lacunar stroke ( mean age , 63.3±10.8 years ) , there were 115 major vascular events ( stroke , myocardial infa rct ion , and vascular death ) . The risk of major vascular events increased with elevated concentrations of both tumor necrosis factor-&agr ; receptor 1 ( adjusted HR per SD , 1.21 ; 95 % CI , 1.05–1.41 ; P=0.01 ) and IL-6 ( adjusted HR per SD , 1.10 ; 95 % CI , 1.02–1.19 ; P=0.008 ) . Compared with the bottom quartile ( tumor necrosis factor-&agr ; receptor 1 < 2.24 ng/L ) , those in the top quartile of tumor necrosis factor-&agr ; receptor 1 ( > 3.63 ng/L ) were at twice the risk of major vascular events after adjusting for demographics ( partially adjusted HR , 1.98 ; 95 % CI , 1.11–3.52 ) , though the effect attenuated after adjusting for other risk factors and statin use ( adjusted HR , 1.68 ; 95 % CI , 0.93–3.04 ) . Serum amyloid A , CD40 lig and , and monocyte chemoattractant protein 1 were not associated with prognosis . Conclusions — Among recent lacunar stroke patients , IL-6 and TNF receptor concentrations predict risk of recurrent vascular events , and they are associated with the effect of antiplatelet therapies . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT00059306 |
13,832 | 25,605,584 | QoL was found to be impaired in patients with active disease relative to controls , and generally improved during biochemical cure .
Intervention studies ( predominantly evaluating medical interventions ) have been found to improve QoL. Conclusions The growing number of studies assessing QoL generally described the negative impact of pituitary adenomas .
Surgical and pharmacological interventions improve but not normalize QoL. We postulate that there might be margin for further improvement of QoL , for instance by using psychosocial interventions , in addition to optimal medical treatment | Purpose Pituitary adenomas give rise to physical and psychological symptoms , which may persist after biochemical cure .
Growing attention has been paid to quality of life ( QoL ) in these patients .
We aim ed to systematic ally analyze QoL assessment methods and QoL outcome in these patients . | OBJECTIVE The European Registry on Cushing 's syndrome ( ERCUSYN ) is design ed to collect prospect i ve and follow-up data at EU level on Cushing 's syndrome ( CS ) . DESIGN AND METHODS Baseline data on 481 CS patients ( 390 females , 91 males ; mean age ( ±s.d . ) : 44±14 years ) collected from 36 centres in 23 countries , including new patients from 2008 and retrospective cases since 2000 . Patients were divided into four major aetiologic groups : pituitary-dependent CS ( PIT-CS ) ( 66 % ) , adrenal-dependent CS ( ADR-CS ) ( 27 % ) , CS from an ectopic source ( ECT-CS ) ( 5 % ) and CS from other aetiologies ( 2 % ) . RESULTS Proportion of men in the ECT-CS group was higher than in the other groups ( P<0.05 ) . The ADR-CS group was older than the PIT-CS ( P<0.05 ) . Prevalence of hirsutism ( 92 % ) and diabetes ( 74 % ) in ECT-CS was higher than in the other groups ( P<0.05 and P<0.01 respectively ) . PIT-CS had more skin alterations , menstrual irregularities and hirsutism than ADR-CS ( P<0.01 ) . Reduced libido was more prevalent in men than women ( P<0.01 ) . Prevalence of spine osteoporosis was higher in men than women ( P<0.05 ) , and males had more vertebral and rib fractures than females ( 52 vs 18 % for vertebrae ; P<0.001 and 34 vs 23 % for ribs ; P<0.05 ) . ECT-CS consulted a diabetologist more frequently than ADR-CS ( P<0.05 ) , while a gynaecologist was consulted more often by women with PIT-CS or ADR-CS than with ECT-CS ( P<0.05 ) . Overall , weight gain was more common in women than men ( P<0.01 ) . CushingQoL and EuroQoL visual analogue scale scores did not differ between the groups . CONCLUSIONS The ERCUSYN project demonstrates a heterogeneous clinical presentation of CS at a European level , depending on gender and aetiology The aim of this study was to assess the effects of replacement with recombinant human growth hormone ( rhGH ) in patients with GH deficiency ( GHD ) after treatment of acromegaly . Intervention study . Sixteen patients ( 8 men , age 56 years ) , treated for acromegaly by surgery and radiotherapy , with an insufficient GH response to insulin-induced hypoglycaemia , were treated with 1 year of rhGH replacement . Study parameters were assessed at baseline and after 1 year of rhGH replacement . Study parameters were cardiac function , body composition , bone mineral density ( BMD ) , fasting lipids , glucose , bone turnover markers , and Quality of Life ( QoL ) . During rhGH replacement IGF-I concentrations increased from −0.4 ± 0.7 to 1.0 ± 1.5 SD ( P = 0.001 ) , with a mean daily dose of 0.2 ± 0.1 mg in men and 0.3 ± 0.2 mg in women . Nonetheless , rhGH replacement did not alter cardiac function , lipid and glucose concentrations , body composition or QoL. Bone turnover markers ( PINP and β crosslaps ) levels increased ( P = 0.005 and P = 0.021 , respectively ) , paralleled by a small , but significant decrease in BMD of the hip . The beneficial effects of rhGH replacement in patients with GHD during cure from acromegaly are limited in this study OBJECTIVE To develop and test the psychometric properties of a 25-item version of the National Eye Institute Visual Function Question naire ( NEI VFQ-25 ) . DESIGN Prospect i ve observational cohort study of persons with 1 of 5 chronic eye diseases or low vision who were scheduled for nonurgent visits in ophthalmology practice s and a reference sample of persons without eye disease . SETTING Eleven university-based ophthalmology practice s and the NEI Clinical Center . PATIENTS Eligible participants had to have 1 of the following eye conditions : age-related cataracts , age-related macular degeneration , diabetic retinopathy , primary open-angle glaucoma , cytomegalovirus retinitis , or low vision from any cause . Seven of the 12 sites also enrolled persons in a reference sample . Reference sample participants had no evidence of underlying eye disease but were scheduled for either screening eye examinations or correction of refractive error . All eligible persons had to be 21 years or older , English speaking , and cognitively able to give informed consent and participate in a health status interview . MEASUREMENTS AND MAIN RESULTS To provide the data needed to create the NEI VFQ-25 , all subjects completed an interview that included the 51-item NEI VFQ . Estimates of internal consistency indicate that the subscales of the NEI VFQ-25 are reliable . The validity of the NEI VFQ-25 is supported by high correlations between the short- and long-form versions of the measure , observed between-group differences in scores for persons with different eye diseases of varying severity , and the moderate-to-high correlations between the NEI VFQ-25 subscales that have the most to do with central vision and measured visual acuity . CONCLUSIONS The reliability and validity of the NEI VFQ-25 are comparable to those of the 51-item NEI VFQ field test version of the survey . This shorter version will be more feasible in setting s such as clinical trials where interview length is a critical consideration . In addition , preliminary analyses indicate that the psychometric properties of the NEI VFQ-25 are robust for the eye conditions studied ; this suggests that the measure will provide reproducible and valid data when used across multiple conditions of varying severity Objective To verify whether patients with pituitary disorders in remission and on appropriate treatment display significant differences in psychological distress compared to healthy controls and other patients treated for nonpituitary endocrine disorders OBJECTIVE Vali date the acromegaly quality of life ( AcroQoL ) question naire as a disease-generated question naire , which analyses physical and psychological domains , the latter subdivided into appearance and personal relationship sub-scales , to evaluate health-related quality of life ( HRQoL ) in acromegaly . DESIGN Prospect i ve , observational multicenter study . METHODS One hundred and six patients with acromegaly , 42 with active disease studied basally and 6 months after treatment ( ' sensitivity to change ' group ) , and 64 with treated , stable disease , studied twice within 1 month ( ' reliability ' group ) were included . As controls , a reference Spanish population ( n=12,245 for the EuroQoL question naire ) and 157 obese patients ( body mass index>30 kg/m2 ) were studied basally . Socio-demographic data , clinical activity , co-morbidity , GH , IGF-I , and HRQoL ( overall perception of health state , EuroQoL and AcroQoL in the obese controls and acromegalic patients ) were evaluated . RESULTS Globally , AcroQoL scored worse in the ' sensitivity to change ' group than in the ' reliability ' group ( 56+/-20 vs 65+/-18 , P<0.05 ) , but did not discriminate between patients and obese controls . The psychological domain was worse in the ' sensitivity to change ' group than obese controls ( P<0.05 ) . Appearance was the most affected sub-scale in acromegaly and significantly worse than in obese controls . The sub-scale personal relationships of AcroQoL were less affected in the ' reliability ' group than in obese controls ( P<0.05 ) . Patients with acromegaly and obese controls showed more problems on the EuroQoL than general Spanish population . Significant correlations were observed globally and for each dimension between AcroQoL and the generic question naires . On re-testing , no change was observed in the ' reliability ' group in any question naire , demonstrating good test-re-test reliability . In the ' sensitivity to change ' group after 6 months of treatment , there was improvement in the generic question naires and in AcroQoL score ( P<0.01 ) . Internal consistency of AcroQoL was good ( Cronbach 's alpha>0.7 ) . No correlation between AcroQoL and GH or IGF-I was observed . CONCLUSION AcroQoL question naire is a valid tool for the assessment of HRQoL in clinical practice in patients with acromegaly CONTEXT Cotreatment of acromegaly with pegvisomant and a somatostatin analog ( SA ) has proven feasible . Previous studies in the field have focused on patients with an insufficient response to SA monotherapy in whom pegvisomant was added without changing the SA dose . OBJECTIVE The objective of the study was to study whether patients sufficiently controlled on SA monotherapy can be transferred to combination therapy with low-dose pegvisomant and a reduced SA dose . DESIGN Eighteen acromegalic patients well controlled on SA monotherapy , mean ± se aged 54 ± 3 yr , were r and omized in a parallel study over 24 wk to unchanged SA monotherapy or cotreatment with pegvisomant ( 15 - 30 mg twice a week ) and SA ( half the usual dosage ) . SETTING This was an investigator-initiated study in a single tertiary referral center . MAIN OUTCOME MEASURES Glucose tolerance , substrate metabolism , insulin sensitivity , body composition , and quality of life were measured . RESULTS Median pegvisomant dose was 52.5 mg/wk ( range 30 - 60 ) . IGF-I ( micrograms per liter ) was comparable both at baseline ( P = 0.88 ) and after 24 wk of treatment ( P = 0.48 ) . The change in IGF-I between baseline and wk 24 also did not differ between groups ( P = 0.15 ) . Apart from increased peak insulin levels during the oral glucose tolerance test in the cotreatment group , no substantial differences between the two groups were detected . Moderately elevated liver enzymes were found in 17 % of the patients on pegvisomant therapy . CONCLUSION Acromegalic patients well controlled on SA monotherapy can maintain safe IGF-I levels during 24 wk of cotreatment with low-dose pegvisomant and a 50 % reduced SA dose . This treatment modality , however , does not seem to provide significant benefits for the patients Background There is a paucity of research about health-related quality of life ( HRQL ) among adolescents , as studies have to a large extent focused on adults . The main aim was to provide information for future studies in this growing field by presenting normative data for the Short Form 36 ( SF-36 ) and the Hospital Anxiety and Depression Scale ( HADS ) for Swedish adolescents and young adults . Additionally , the influence of age and gender , as well as method of administration , was investigated . Methods A sample of 585 persons aged 13–23 was r and omly chosen from the general population , and stratified regarding age group ( young adolescents : 13–15 years ; older adolescents : 16–19 years , and young adults : 20–23 years ) and gender ( an equal amount of males and females ) . Within each stratum , the participants were r and omized according to two modes of administration , telephone interview and postal question naire , and asked to complete the SF-36 and the HADS . Descriptive statistics are presented by survey mode , gender , and age group . A gender comparison was made by independent t-test ; and one-way ANOVA was conducted to evaluate age differences . Results Effects of age and gender were found : males reported better health-related quality of life than females , and the young adolescents ( 13–15 years old ) reported better HRQL than the two older age groups . The older participants ( 16–23 years old ) reported higher scores when interviewed over the telephone than when they answered a postal question naire , a difference which was more marked among females . Interestingly , the 13–15-year-olds did not react to the mode of administration to the same extent . Conclusion The importance of taking age , gender , and method of administration into consideration , both when planning studies and when comparing results from different groups , studies , or over time , is stressed The purpose of the study was to evaluate changes in general self-efficacy , health related quality of life ( HRQoL ) , and stress among patients with neuroendocrine tumors ( NET ) following a multidisciplinary educational intervention . Forty-one patients were enrolled in this exploratory pilot study . A total of 37 patients completed the full 26-week intervention based on the principles of self-efficacy . General self-efficacy was measured by the General Self-Efficacy Scale , HRQoL was measured with the SF-36 , and stress was measured with the Impact of Event Scale . Mixed effect models were used to evaluate changes in general self-efficacy , mental and physical components of HRQoL , and stress adjusting for demographic and clinical variables . Results showed significant improvements in patients ' general self-efficacy ( β = 0.71 ; P < 0.05 ) , physical component scores of HRQoL ( β = 3.09 ; P < 0.01 ) , and stress ( β = −2.10 , P = 0.008 ) . Findings suggest that patients with NET have the capacity to improve their ability to cope with their disease , problem-solve , improve their physical status , and reduce their stress following an educational intervention based on the principles of self-efficacy . These preliminary data provide a basis for future r and omized controlled trials to test interventions to improve HRQoL for patients with NET Mifepristone , a glucocorticoid receptor antagonist , improves clinical status in patients with Cushing 's syndrome ( CS ) . We examined the pattern , reliability and correlates of global clinical response ( GCR ) assessment s during a 6‐month clinical trial of mifepristone in CS The objective of this study was to provide normative SF-36 scores in a general population sample in Brazil and to describe differences in mean scores according to socio-demographic characteristics . The SF-36 question naire was distributed to a r and omly selected sample of the general population of Porto Alegre in the State of Rio Gr and e do Sul . The response rate was 68 % and 755 subjects were included ( 38 % male , 62 % female ) . Lower health status was revealed among females in the 30 to 44 year age bracket , from the lower income class , with less education and self-reported chronic medical conditions . The results and percentiles of scores of the SF-36 are reported as normative data for the general population . The SF-36 was an acceptable and practical instrument for measuring health-related quality of life in a sample of Brazilians . The results of this study can be useful for research ers using the SF-36 question naire in other groups to compare the scores with normative data . The SF-36 may prove a valuable tool for discovering vulnerable groups in epidemiological studies due to the ability to discriminate between different population subgroups OBJECTIVE Acromegaly has an important impact on quality of life ( QOL ) . The aim of this study was to evaluate the associations of remission status and lanreotide treatment with QOL in patients with treated acromegaly , by the newly developed disease-generated acromegaly QOL question naire ( ACROQOL ) . DESIGN Cross-sectional study . METHODS Fifty-two patients with treated acromegaly were recruited to complete the Chinese version of the ACROQOL translated and vali date d from the English version . These patients were divided into controlled and uncontrolled groups based on the latest remission criteria and further subdivided into four groups according to the present treatment with lanreotide or not . Comparisons between groups were analyzed . RESULTS There was no difference between controlled and uncontrolled groups in the ACROQOL scores of total score , both scales and psychological subscales . However , in the controlled group , present treatment with lanreotide , in comparison with no treatment , showed worse ACROQOL scores in total score ( P = 0.021 ) , psychological scale ( P = 0.011 ) , psychological subscale ' appearance ' ( P = 0.032 ) and ' personal relations ' ( P = 0.010 ) . CONCLUSIONS The lanreotide treatment was negatively associated with QOL in biochemically controlled acromegalic patients , especially in the psychological aspect A vali date d quality of life ( QOL ) measure , the SF-36 question naire , was used to assess patients ' perception of the impact of a pituitary adenoma , prior to treatment , on his or her physical and mental functioning . Of 270 new patients evaluated for pituitary disease at the University of Virginia Pituitary Clinic , 168 met the criteria for inclusion ( pituitary hormone hypersecretion and /or pituitary adenoma ) into this prospect i ve study . Results of the SF-26 question naire in 36 patients with acromegaly , 42 patients with Cushing 's disease , 39 patients with a prolactinoma and 51 patients with a non functioning macroadenoma prior to treatment were compared with those of the normal population ; a comparison of results among patients with different types of pituitary adenomas was also performed . Patients with a pituitary adenoma had a significantly decreased QOL compared with the normal population in both physical and mental measures ( p < 0.05 ) . There were different degrees of perceived impairment depending on the type of pituitary adenoma . Patients with acromegaly had impairment in measures of physical function while patient with Cushing 's disease had impairment in all but one measures compared with the normal population and with patients with other types of pituitary adenomas . Patients with a prolactinoma had impairment in mental measures and patients with a non-functioning adenoma had impairment in both physical and mental measures compared with the normal population . Patients with a pituitary adenoma have an impaired quality of life that should be routinely assessed in conjunction with endocrine and anatomic studies before and after treatment CONTEXT Recent studies have suggested that long-term exposure to high levels of GH and IGF-I affect brain and cognitive functions . However , very few human studies have challenged this hypothesis . OBJECTIVE The aim of this study is to explore whether GH/IGF-I excess in naive patients with acromegaly alters cognitive functions , particularly memory , and whether these alterations are accompanied by neurophysiological correlates . DESIGN We conducted a comprehensive neuropsychological and neurophysiological exam on 16 naive acromegaly patients and 16 strictly matched healthy controls . Comparative analyses were carried out on major neurocognitive domains ( executive functions , visual/verbal memory , attention , visuoconstructive abilities , and verbal fluency ) and on quantitative electroencephalogram and low-resolution brain electromagnetic tomography sources . Results were correlated with GH and IGF-I hormone concentrations . RESULTS Short- and long-term memory were the most severely impaired cognitive functions . Moreover , memory performance correlated negatively with GH and IGF-I concentrations . No association was detected between depression and memory impairment , and only a marginal association was found with quality of life . Finally , acromegaly patients showed power attenuation in fast frequency electroencephalogram b and s , as well as decreased activity in prefrontal and middle temporal cortices , that was associated to cognitive performance . CONCLUSIONS Results provide evidence of cognitive and neurophysiological impairment , characterized by moderate-to-severe memory impairment and decreased neural activity in specific brain areas . High levels of GH and IGF-I in acromegaly patients could be the basis for these findings BACKGROUND Normalization of IGF-I in patients with acromegaly is associated with a decrease in mortality . Pegvisomant may be more effective in lowering IGF-I than octreotide . SUBJECTS AND METHODS The efficacy and safety of pegvisomant and octreotide long-acting release ( LAR ) were compared in 118 patients with acromegaly in this 52-week , multicenter , open-label , r and omized study . The primary endpoint was IGF-I normalization at week 52 . Secondary endpoints included mean changes from baseline in IGF-I , IGF binding protein 3 , acromegaly signs and symptom scores , ring size , acromegaly quality of life question naire scores , and safety . RESULTS Fifty-six patients received pegvisomant and 57 received octreotide LAR . IGF-I normalized in 51 % of pegvisomant patients and 34 % treated with octreotide LAR ( p=0.09 , ns ) . Patients with baseline IGF-I > or = 2x upper limit of normal had a higher rate of IGF-I normalization with pegvisomant vs octreotide LAR ( p=0.05 ) . Among the patients who did not achieve a normalized IGF-I , pegvisomant-treated patients were more likely to be receiving < 30 mg of study drug ( 71 % vs 16 % ) . Treatment-related adverse events were mild-to-moderate in both groups . Mean fasting glucose decreased in diabetic and non-diabetic patients on pegvisomant whereas octreotide LAR was associated with an increase at week 52 ( p=0.005 and p=0.003 between groups , respectively ) . Mean change in tumor volume during treatment was similar between groups . CONCLUSIONS Pegvisomant and octreotide LAR were equally effective in normalizing IGF-I in the overall population , and pegvisomant was more effective in patients with higher baseline IGF-I levels . Pegvisomant had a more favorable effect on parameters of glycemic control OBJECTIVES To investigate the quality of life ( QoL ) in acromegalic patients in relation to biochemical parameters . DESIGN AND METHODS Single-center , open label study in 14 acromegalic patients ( eight woman and six men , age 33 - 77 years ) , with normal serum IGF-I levels during long-term treatment with monthly injections of 20 mg of long-acting octreotide . We investigated which biochemical parameter might reflect optimal QoL , using the SF-36 question naire . RESULTS We observed that six patients had a low QoL score at baseline in the same range as observed in cancer patients . The other eight patients had a normal QoL. GH , IGF-I nor free IGF-I could discriminate these two subgroups at baseline . After skipping one monthly injection , all six subjects with the low QoL escaped in their free IGF-I concentrations . Also total IGF-I concentrations escaped in four of these six . In the subjects with normal QoL , free IGF-I levels remained normal in all , while total IGF-I levels only escaped in one . CONCLUSIONS This study tells us that the currently used biochemical criteria for disease control in acromegaly might be sufficient in assessing long-term mortality and morbidity , but they are insufficient in addressing the most important parameter from the patient 's perspective -- Abstract Purpose : To develop a mapping algorithm for the estimation of EQ-5D-based utility scores from observed 25-item National Eye Institute Visual Functioning Question naire ( NEI VFQ-25 ) scores , a disease-specific , patient-reported outcome measure used in several retinal disorders to evaluate vision-specific functioning . Methods : The data set comprised 951 paired EQ-5D/NEI VFQ-25 observations from 344 patients in RESTORE , a 12-month , r and omized , double-blind trial in individuals with visual impairment due to diabetic macular edema . EQ-5D index scores ( utilities ) were calculated based on the UK tariff . We evaluated 11 models using predictor sets based on the NEI VFQ-25 subscales to estimate utility as a function of NEI VFQ-25 score , based on four modeling techniques . Model performance was assessed by 10-fold cross-validation comparing root mean squared error ( RMSE ) , mean absolute error ( MAE ) and correlation with EQ-5D score ( Pearson and Spearman correlation coefficients ) . Results : Mapping results were similar across all techniques and predictor sets . The reverse two-part generalized estimating equation model used fewest predictors and had the best predictive performance ( RMSE 0.200 , MAE 0.140 ) . Predicted and original EQ-5D values were not strongly correlated ( squared Spearman correlation coefficient , 0.34 ) . Conclusions : Although mapping disease-specific instruments to EQ-5D utilities is a preferred method by some reimbursement bodies , finding an appropriate mapping equation is not straightforward . In this study , mapping NEI VFQ-25 scores to EQ-5D utilities provided low predictive power , independent of the modeling methodology applied , suggesting an inability of the EQ-5D to discriminate vision-related activities , and highlighting that mapping exercises may lead to inaccurate utility values that do not represent patients ’ preferences Objective : To evaluate efficacy and safety of lanreotide autogel ( ATG ) 120 mg injections every 4–8 weeks in somatostatin analogue-na"ive patients with acromegaly . Design : Open , non-comparative , phase III , multicenter clinical study . Methods : Fifty-one patients ( 28 women , aged 19–78 yr ) : 39 newly diagnosed ( de novo ) and 12 who had previously undergone unsuccessful surgery ( post-op , 11 macro and 1 micro ) were studied . ATG 120 mg was initially given every 8 weeks for 24 weeks and subsequently changed according to GH levels : if ≤2.5 μg/l every 8 weeks ( group A , 17 patients ) ; if 2.5–5 μg/l every 6 weeks ( group B , 15 patients ) ; and if > 5 μg/l every 4 weeks ( group C , 19 patients ) . Treatment duration was 48–52 weeks . The primary objective was to control GH and IGF-I levels ( GH≤2.5 μg/l and IGF-I normalized for age/gender ) . Secondary objectives were to assess GH , IGF-I , and acid-labile subunit ( ALS ) decrease , improvement of clinical symptoms and quality of life ( QoL ) . Results : GH levels normalized in 32 patients ( 63 % ) , similarly in de novo and post-op patients ( 72 % vs 50 % , p=0.48 ) ; in 100 % of group A , in 73 % of group B and in 21 % of group C ( p<0.0001 ) . IGF-I levels normalized in 19 patients ( 37 % ) , similarly in the de novo and post-op patients ( 33 % vs 50 % , p=0.48 ) : in 65 % of group A , 33 % of group B , and in 16 % of group C. Circulating GH levels decreased by 80±17 % , IGF-I levels by 44±27 % , and ALS by 30±17 % . Symptoms ( hyperhidrosis ( 68.6 % ) , swelling ( 68.6 % ) , asthenia ( 58.8 % ) , spine arthralgia ( 54.9 % ) , and paresthesias ( 52.9 % ) and QoL ( from 9.1 ±7.9 to 6.1 ±6.6 ) significantly improved ( p<0.001 ) . No patient withdrew from the study because of adverse events ( AE ) . The most frequent AE was diarrhea ( 76.2 % of patients ): at study end 16 mild and 1 moderate diarrhea were recorded . Gallstones developed in 12 % of patients . Conclusion : ATG 120 mg in somatostatin-naïve patients with acromegaly controls GH secretion in 63 % and IGF-I secretion in 37 % during a 48–52 week period without any difference between de novo and post-op patients . The treatment was associated with improvement in clinical symptoms and QoL and with a good , safe profile BACKGROUND The Medical Outcomes Study 36-item Short Form ( SF-36 ) is a widely used measure of health-related quality of life . Normative data are the key to determining whether a group or an individual scores above or below the average for their country , age or sex . Published norms for the SF-36 exist for other countries but have not been previously published for Canada . METHODS The Canadian Multicentre Osteoporosis Study is a prospect i ve cohort study involving 9423 r and omly selected Canadian men and women aged 25 years or more living in the community . The sample was drawn within a 50-km radius of 9 Canadian cities , and the information collected included the SF-36 as a measure of health-related quality of life . This provided a unique opportunity to develop age- and sex-adjusted normative data for the Canadian population . RESULTS Canadian men scored substantially higher than women on all 8 domains and the 2 summary component scales of the SF-36 . Canadians scored higher than their US counterparts on all SF-36 domains and both summary component scales and scored higher than their UK counterparts on 4 domains , although many of the differences are not large . INTERPRETATION The differences in the SF-36 scores between age groups , sexes and countries confirm that these Canadian norms are necessary for comparative purpose s. The data will be useful for assessing the health status of the general population and of patient population s , and the effect of interventions on health-related quality of life OBJECTIVE To compare the response in quality of life ( QoL ) to growth hormone ( GH ) replacement in women with GH deficiency ( GHD ) and a history of acromegaly with that in women with GHD of other causes . METHODS Fifty-five women with GHD were studied : 17 with prior acromegaly and 38 with other causes of GHD . We compared two 6-month , r and omized , placebo-controlled studies of GH therapy in women with hypopituitarism conducted with use of the same design -one in women with a history of acromegaly and one in women with no prior acromegaly . QoL was assessed with the following question naires : the QoL- Assessment of Growth Hormone Deficiency in Adults ( AGHDA ) , the Symptom Question naire , and the 36-Item Short-Form Health Survey ( SF-36 ) . RESULTS The 2 groups had comparable mean pretreatment age , body mass index , and QoL scores and comparable mean GH dose at 6 months ( 0.61 ± 0.30 versus 0.67 ± 0.27 mg daily ) . After 6 months of GH replacement therapy , women with GHD and prior acromegaly demonstrated a greater improvement in AGHDA score , four SF-36 sub-scales ( Role Limitations due to Physical Health , Energy or Fatigue , Emotional Well-Being , and Social Functioning ) , and the Somatic Symptoms subscale of the Symptom Question naire than did women with GHD of other causes . Poorer pretreatment QoL was associated with a greater improvement in QoL after administration of GH . CONCLUSION In this study , GH replacement therapy improved QoL in women with GHD and a history of acromegaly but not in women with GHD due to other hypothalamic and pituitary disorders . Further studies are needed to determine the long-term risks versus benefits of GH replacement in patients who develop GHD after definitive treatment for acromegaly Anchoring health-related quality of life ( HRQOL ) measures in population norms makes clinical interpretations more meaningful and is in accordance with practice in other fields of medicine . In this paper norms for the Short Form 36 ( SF-36 ) are presented in a r and om sample , representative of the general Norwegian population . In addition , sociodemographic variables affecting the scale scores are explored and discussed . The response rate was 67 % , being lowest among subjects aged 70 years or over . Data -completeness strongly declined with increasing age . Physical health scales were also strongly affected by age . In all scales , with the exception of general health perceptions , women reported having poorer health than men . Marital status affected the four mental health scales . Educational status affected all the scales , but the effect was smallest in the mental scales . These norms can be employed for comparison in case-control studies , or to interpret HRQOL changes in prospect i ve studies . Differences in social status should be given special attention . Caution should be exercised when assessing subjective health or employing the norms among subjects aged 70 years or over The long-term efficacy and tolerability of CV 205 - 502 , a non-ergot dopamine agonist with D-2 receptor affinity , were studied for up to 36 months in 16 patients with macroprolactinomas . Prolactin values were reduced in all cases , becoming either normalized or suppressed in 12 . The pituitary tumor size was reduced in the 13 patients with an obvious tumor and visual function normalized in all six patients with initial defects . Concomitantly we observed improvement in gonadal function , galactorrhea , headache , libido and general well-being . Adverse reactions were experienced by 15 patients during dosage increment and caused one patient to discontinue the medication . Seven patients had persistent adverse effects which prohibited a dosage increase of CV 205 - 502 , sufficient to normalize PRL levels in three . Two patients experienced serious adverse events , causing the discontinuation of treatment in one case . In eight patients treatment with CV 205 - 502 and bromocriptine could be compared . Three patients responded better to CV 205 - 502 than to bromocriptine treatment . Only one patient preferred bromocriptine to CV 205 - 502 for long-term treatment . We conclude that CV 205 - 502 is an effective and in most cases well-tolerated treatment for patients with macroprolactinomas . CV 205 - 502 is preferable to bromocriptine as an initial treatment and should also be tried in patients where treatment with bromocriptine has failed Background Generic measures of quality of life have a wide application in health research . They measure disease impact by comparing scores in patient groups with a healthy population . They also facilitate comparative studies between different : patient groups . The SF-36 Health Survey quantifies respondents ’ perceptions of their functioning in eight dimensions of daily life . Aim The aim of this study was to set normative values for the SF-36 in the Irish population aged 18 years and over . Method A r and om sample of 800 subjects was drawn from the electoral register using the RANSAM method of sampling . Results Two hundred and ninety five ( 37 % ) valid question naires were returned for analysis . The SF-36 was found to have acceptable internal consistency and validity . Normative values for the total population are presented , in addition to results for males and females across seven age groups . Ageing was associated with a decline in the physical dimensions of health . Conclusions There was no evidence to suggest that there were significant differences in health status between mates and females , or between this Irish sample and the published norms for the US population Quality of life ( QoL ) may be affected in acromegalic patients , although the role of disease activity is still unsettled . The aim of the study was to assess the QoL of acromegalic patients with a specific question naire ( ACROQOL ) . ACROQOL was evaluated in a prospect i ve study ( at baseline , at 6 and 24 months ) in 23 active untreated acromegalic patients . Control of acromegaly was defined by normal age-matched serum IGF-I concentrations . Patient groups were defined as controlled or uncontrolled at 6 months and at 24 months : controlled or uncontrolled during the entire study period ( ACROCC or ACRONC , respectively ) or uncontrolled at 6 months and controlled thereafter ( ACROC ) . At 6 months , ACROQOL scores improved globally ( from 54.3±21 to 65.1±19 , p=0.04 ) as did subdomains and were inversely related to IGF-I variation ( r=−0.50 , p=0.052 ) . At 24 months , ACROQOL improved globally ( from 54.3±21 to 65.7±18.0 , p=0.04 ) and this was also seen in the appearance subdomains ; however , no correlation was revealed between variation of serum IGF-I concentrations and changes in ACROQOL total score ( r=0.008 , p=0.87 ) . ACROQOL scores did not significantly change in ACRONC ( p=0.310 ) and in ACROC ( p=0.583 ) , whereas it improved globally ( from 42.1±22.1 to 58.8±16.04 , p=0.021 ) and in psychological subdomains in ACROCC ; however , it reflected the improvement occurred within the first 6 months of disease control . In conclusion , successful treatment , which normalizes disease activity , improves QoL in acromegaly in the short term . However , the lack of correlation between the ACROQOL score in the long term might suggest that factors other than serum IGF-I participate in the well-being of acromegalic patients ; however , due to the small sample size , our results need to be confirmed in larger studies Objectives To evaluate QOL in women with microprolactinomas treated with dopamine agonists , comparing the patients with normal versus those with elevated prolactin levels , and to identify clinical and biochemical influences on patients ’ QOL . Material and methods A cross-sectional evaluation was performed in two University referral centers . Fifty women with microprolactinoma answered the SF-36 question naire by the time of their clinical evaluation . Their biochemical analysis included PRL , estradiol , testosterone , and SHBG . Fifty women of similar age distribution served as controls . Results Patients had lower scores than controls in all SF-36 categories : physical functioning , physical role , pain , general health , vitality , social functioning , emotional aspect , and mental health . Within the patients ’ group , the ones with normal PRL levels had higher scores than those with high PRL levels in all categories but the physical role . The physical functioning score correlated with the free and rogen index , while the pain , vitality , social functioning , emotional aspect , and mental health scores were associated with the prolactin levels obtained at study entry . Conclusions QOL is impaired in women with microprolactinoma treated with dopamine agonists , and was inversely associated with the PRL levels . This latter finding reinforces the importance of providing adequate disease control for these patients in order to avoid the adverse consequences of hyperprolactinemia on QOL OBJECTIVE The objective of the study was to assess whether weekly administration of 40 mg pegvisomant ( PEG-V ) improves quality of life ( QoL ) and metabolic parameters in acromegalic patients with normal age-adjusted IGF-I concentrations during long-acting somatostatin analog ( SSA ) treatment . DESIGN This was a prospect i ve , investigator-initiated , double blind , placebo-controlled , crossover study . Twenty acromegalic subjects received either PEG-V or placebo for two consecutive treatment periods of 16 wk , separated by a washout period of 4 wk . Efficacy was assessed as change between baseline and end of each treatment period . QoL was assessed by the Acromegaly Quality of Life Question naire ( AcroQoL ) and the Patient-Assessed Acromegaly Symptom Question naire ( PASQ ) . RESULTS The AcroQoL ( P = 0.008 ) and AcroQoL physical ( P = 0.002 ) improved significantly after PEG-V was added . The addition of PEG-V also significantly improved the PASQ ( P = 0.038 ) and the single PASQ questions , perspiration ( P = 0.024 ) , soft tissue swelling ( P = 0.036 ) , and overall health status ( P = 0.035 ) . No significant change in Z-score of IGF-I ( P = 0.34 ) was observed during addition of PEG-V. Transient liver enzyme elevations were observed in five subjects ( 25 % ) . CONCLUSION Improvement in quality of life was observed without significant change in IGF-I after the addition of 40 mg pegvisomant weekly to monthly SSA therapy in acromegalic patients who had normalized IGF-I on SSA monotherapy . These data question the current recommendations in how to assess disease activity in acromegaly . Moreover , the findings question the validity of the current approach of medical treatment in which pegvisomant is used only when SSA therapy has failed to normalize OBJECTIVE To assess the efficacy of different dosing intervals of lanreotide , Somatuline Autogel ® ( Lan-ATG ) 120 mg in patients with acromegaly , previously treated with octreotide , long-acting release ( Oct-LAR ) . PATIENTS AND STUDY DESIGN Patients previously on Oct-LAR 10 , 20 , or 30 mg were switched to 6 repeated deep subcutaneous injections of Lan-ATG 120 mg at intervals of 56 , 42 , or 28 days , respectively . After the third injection , dose intervals were adjusted on the basis of insulin-like growth factor 1 ( IGF-1 ) levels . RESULTS The ITT ( Intention To Treat ) population comprised 35 patients who received at least one dose of study medication and at least one post-baseline efficacy assessment . Overall , 62.9 % ( n=22 ) of patients had normalised IGF-1 levels with Lan-ATG at study end ( one injection interval after the 6 ( th ) injection of Lan-ATG ) , which was similar to the proportion at baseline ( 60.0 % [ n=21 ] ) . QoL did not change from baseline to study end . Patient preference for Lan-ATG was highest in the 56-day dosing interval group : 71 % , 54 % and 41 % of the patients in the 56 , 42 and 28 day groups , respectively , expressed a preference for treatment with Lan-ATG ( preference for Oct-LAR : 29 % , 9 % and 35 % , respectively , while the remainder had no preference ) . CONCLUSION Lan-ATG 120 mg injected at intervals of 56 , 42 and 28 days provided equivalent hormonal control and QoL to Oct-LAR 10 , 20 and 30 mg injected every 28 days , respectively . The proportion of patients preferring Lan-ATG treatment was greater in the longer injection interval groups |
13,833 | 21,601,591 | Meta- analysis shows that computer-based interventions were effective in increasing FV consumption .
Multicomponent interventions and free/subsidized FV interventions were not effective .
Although these results are preliminary , computer-based interventions could be considered in schools , given that they are effective and cheaper than other alternatives | OBJECTIVE The consumption of fruits and vegetables ( FV ) may contribute to the prevention of many diseases .
However , children at school age do not eat an enough amount of those foods .
We have systematic ally review ed the literature to assess the effectiveness of school interventions for promoting the consumption of FV . | Aims : To estimate the impact of school fruit tuck shops on children ’s consumption of fruit and sweet and savoury snacks . Design : Cluster r and omised effectiveness trial with school as the unit of r and omisation . Setting : 43 primary schools in deprived areas in south Wales and south-west Engl and with a range of school food policies . Intervention : Schools operated fruit tuck shops throughout one academic year . Control schools did not do so . Measures : Repeated cross-sections of children aged 9–11 years completed a computerised 24-hour recall question naire at baseline ( n = 1902 ) and at 1-year follow-up ( n = 1924 ) , when a brief question naire was also completed ( n = 1976 ) . Results : Approximately 70 000 fruits were sold in the 23 intervention schools over the year , equivalent to 0.06 fruits per student per day . Children in intervention schools were more likely to report eating fruit as a snack at school ‘ often ’ ( OR 1.49 , 95 % CI 1.15 to 1.95 ) . There were no significant differences in children ’s intake of fruit or other snacks . There was a significant interaction ( p<0.02 ) between the intervention group and school food policy : where students were only allowed to bring fruit to school , fruit consumption was 0.37 portions per day ( 0.11 to 0.64 ) higher in intervention schools , compared to 0.14 portions ( −0.30 to 0.58 ) where no food was allowed and −0.13 portions ( −0.33 to 0.07 ) where there were no restrictions . Conclusions : In isolation , fruit tuck shops were not effective in changing children ’s snacking behaviour in schools . However , the results suggest that fruit tuck shops had a greater impact when reinforced by school policies restricting the types of foods students were allowed to bring to school Study objective : To examine associations between food and nutrient intake , measured in childhood , and adult cancer in a cohort with over 60 years follow up . Design and setting : The study is based on the Boyd Orr cohort . Intake of fruit and vegetables , energy , vitamins C and E , carotene , and retinol was assessed from seven day household food inventories carried out during a study of family diet and health in 16 rural and urban areas of Engl and and Scotl and in 1937–39 . Participants : 4999 men and women , from largely working class background s , who had been children in the households participating in the pre-war survey . Analyses are based on 3878 traced subjects with full data on diet and social circumstances . Main results : Over the follow up period there were 483 incident malignant neoplasms . Increased childhood fruit intake was associated with reduced risk of incident cancer . In fully adjusted logistic regression models , odds ratios ( 95 % confidence intervals ) with increasing quartiles of fruit consumption were 1.0 ( reference ) , 0.66 ( 0.48 to 0.90 ) , 0.70 ( 0.51 to 0.97 ) , 0.62 ( 0.43 to 0.90 ) ; p value for linear trend=0.02 . The association was weaker for cancer mortality . There was no clear pattern of association between the other dietary factors and total cancer risk . Conclusions : Childhood fruit consumption may have a long term protective effect on cancer risk in adults . Further prospect i ve studies , with individual measures of diet are required to further eluci date these relations Abstract Objective : To assess if a school based intervention was effective in reducing risk factors for obesity . Design : Group r and omised controlled trial . Setting : 10 primary schools in Leeds . Participants : 634 children aged 7 - 11 years . Intervention : Teacher training , modification of school meals , and the development of school action plans targeting the curriculum , physical education , tuck shops , and playground activities . Main outcome measures : Body mass index , diet , physical activity , and psychological state . Results : Vegetable consumption by 24 hour recall was higher in children in the intervention group than the control group ( weighted mean difference 0.3 portions/day , 95 % confidence interval 0.2 to 0.4 ) , representing a difference equivalent to 50 % of baseline consumption . Fruit consumption was lower in obese children in the intervention group ( −1.0 , −1.8 to −0.2 ) than those in the control group . The three day diary showed higher consumption of high sugar foods ( 0.8 , 0.1 to 1.6 ) ) among overweight children in the intervention group than the control group . Sedentary behaviour was higher in overweight children in the intervention group ( 0.3 , 0.0 to 0.7 ) . Global self worth was higher in obese children in the intervention group ( 0.3 , 0.3 to 0.6 ) . There was no difference in body mass index , other psychological measures , or dieting behaviour between the groups . Focus groups indicated higher levels of self reported behaviour change , underst and ing , and knowledge among children who had received the intervention . Conclusion : Although it was successful in producing changes at school level , the programme had little effect on children 's behaviour other than a modest increase in consumption of vegetables . What is already known on this topic Obesity is increasing among school children and dem and s preventive strategies R and omised controlled trials of school based primary prevention programmes have all used a prescriptive approach What this study adds Behavioural changes were disappointing with this programme based on the health promoting schools philosophy , despite changes at school level The only positive outcome was a modest increase in vegetable consumption The discrepancy between changes achieved at the individual and school level raises issues regarding the problems inherent in such Reports of cluster r and omised trials require additional information to allow readers to interpret them accurately The effective reporting of r and omised controlled trials has received useful attention in recent years . Many journals now require that reports conform to the guidelines in the Consoli date d St and ards of Reporting Trials ( CONSORT ) statement , first published in 1996 and revised in 2001 . The statement includes a checklist of items that should be included in the trial report . These items are evidence based whenever possible and are regularly review ed . The statement also recommends including a flow diagram to show the flow of participants from group assignment through to the final analysis . The CONSORT statement focused on reporting parallel group r and omised trials in which individual participants are r and omly assigned to study groups . However , in some situations it is preferable to r and omly assign groups of individuals ( such as families or medical practice s ) rather than individuals . Reasons include the threat of contamination of some interventions ( such as dietary interventions ) if individual r and omisation is used . 5 Also , in certain setting s r and omisation by group may be the only feasible method of conducting a trial . Trials with this design are variously known as field trials , community based trials , place based trials , or ( as in this paper ) cluster r and omised trials . In an earlier discussion paper we considered the implication s of the CONSORT statement for the reporting of cluster r and omised trials . Here we present up date d guidance , based on the 2001 revision of the CONSORT statement OBJECTIVE To measure the effect of a school fruit and vegetable subscription on children 's intake of fruit and vegetables after 5 weeks of intervention . SETTING Seven primary schools in Denmark . DESIGN AND METHODS Intervention schools ( n=4 ) were offered a fruit and vegetable subscription comprising one piece per day . Control schools situated in another municipality were not offered the subscription . Intake of fruit and vegetables was measured at baseline and 5 weeks after the start of the subscription . Two methods were used for dietary assessment : a pre-coded 24-hour recall form including total food intake and a food-frequency question naire ( FFQ ) including only fruit and vegetables . SUBJECTS Children aged 6 - 10 years ( n=804 from intervention schools and n=689 from control schools ) . Response rate in the dietary assessment was 31 % . RESULTS At intervention schools 45 % of the children enrolled in the subscription . After 5 weeks of intervention , both subscribers and non-subscribers had increased their intake of fruit by 0.4 ( P=0.019 ) and 0.3 ( P=0.008 ) pieces per school day , respectively , but no change was observed in vegetable intake . Total intake increased only for non-subscribers by 0.4 piece/school day ( P=0.008 ) mainly due to the consistent increase in fruit intake . No change in intake was measured at control schools . Only the 24-hour recall question naire was sensitive enough to pick up the changes of the subscription , whereas the FFQ was not . CONCLUSION Five weeks with the subscription affected both subscribers and non-subscribers to increase intake of fruit . This may indicate that the subscription had an additional effect of stimulating parents of non-subscribers to supply their children with fruit . The results stress the importance of evaluating the effect of this type of programme , and the carefulness needed in design ing the evaluation study OBJECTIVE To assess the impact of a school-based nutrition education intervention aim ed at increasing the consumption of fruits and vegetables . DESIGN The intervention programme increased the provision of fruits and vegetables in schools and provided a range of point-of-purchase marketing material s , newsletters for children and parents , and teacher information . Curriculum material s at age 6 - 7 and 10 - 11 years were also developed and utilised . Evaluation was undertaken with groups of younger ( aged 6 - 7 years ) and older ( aged 10 - 11 years ) children . Methods included 3-day dietary records with interview and cognitive and attitudinal measures at baseline , with follow-up at 9 months , in intervention and control schools . SETTING The work was undertaken in primary schools in Dundee , Scotl and . SUBJECTS Subjects comprised 511 children in two intervention schools with a further 464 children from two schools acting as controls . RESULTS Children ( n=64 ) in the intervention schools had an average increase in fruit intake ( 133+/-1.9 to 183+/-17.0 g day(-1 ) ) that was significantly ( P<0.05 ) greater than the increase ( 100+/-11.7 to 107+/-14.2 g day(-1 ) ) estimated in children ( n=65 ) in control schools . No other changes in food or nutrient intake were detected . Increases in scores for variables relating to knowledge about fruits and vegetables and subjective norms were also greater in the intervention than in the control group , although taste preferences for fruits and vegetables were unchanged . CONCLUSIONS It is concluded that a whole school approach to increasing intakes of fruits and vegetables has a modest but significant effect on cognitive and attitudinal variables and on fruit intake BACKGROUND This study evaluated the effects of a school-based dietary intervention program to increase fruit and vegetable consumption among fourth- grade rs . METHODS Twenty-eight elementary schools were r and omized to an immediate intervention condition or to a delayed intervention control condition . Measures of diet and psychosocial variables were collected at base line and 1 and 2 years post-baseline . The intervention included classroom , parent , and cafeteria components . RESULTS Mean daily consumption of fruit and vegetables was higher for the intervention children compared with controls at Follow-up 1 ( X(t ) = 3.96 , X(c ) = 2.28 ) and at Follow-up 2 ( X(t ) = 3.20 , X(c ) = 2.21 ) . Macro- and micronutrient changes favoring the intervention children were also observed at both Follow-up 1 and Follow-up 2 . Mean daily consumption of fruit and vegetables was higher for intervention parents compared with controls at Follow-up 1 ( X(t ) = 4.23,X(c ) = 3.94 ) but not at Follow-up 2 . CONCLUSIONS Strong effects were found for the High 5 intervention on fruit and vegetable consumption , on macro- and micro-nutrients , and on psychosocial variables . Future work is needed to enhance the intervention effects on parents ' consumption and to test the effectiveness of the intervention when delivered by classroom teachers This study identified fruit , 100 % juice and vegetables ( FJV ) consumption changes by meal among fourth grade students participating in Squire 's Quest ! , a 10-session individually focused psychoeducational multimedia game with many meal/environment specific behavioral change techniques incorporated into the programming . Participants in 26 elementary schools were r and omly assigned to treatment or control groups . Four days of dietary intake were assessed before and after the intervention to determine FJV servings consumed by meal . Overall , students receiving the intervention consumed 1.0 serving FJV more per day compared with control condition students . Using mixed model analysis of covariance , significant increases were found for servings of fruit and 100 % fruit juice at snacks , and regular vegetables at lunch for intervention school children compared with children in control condition schools . These meals and snacks were targeted by the intervention activities and appear to represent eating occasions for which the children might have had more control . Interventions need to incorporate new procedures to more directly target intake at breakfast and dinner OBJECTIVE To measure the effects of two school-based interventions on children 's intake of fruit and vegetables ( F&V ) . DESIGN AND METHODS A total of six primary schools were r and omly assigned to ( 1 ) a free F&V distribution programme , or ( 2 ) a multicomponent programme , consisting of a classroom curriculum and parental involvement . The two interventions were evaluated on their effects and compared with six control schools in a pre-test-post-test design . Two methods were used for dietary assessment : a pre-structured food recall and a food-frequency question naire including only F&V. SUBJECTS A total of 939 parents of children aged 4 - 12 years filled out the question naire at both pre-test and post-test . The response rate was 54 % . RESULTS Multilevel analyses showed that both programmes were equally effective in increasing children 's fruit consumption by 0.2 portions per day . The free F&V distribution increased vegetable intake among non-native children and the oldest age group , and the multicomponent programme among the oldest children and girls . The distribution also caused an increased 24 h fruit , juice and vegetable intake among the youngest and the oldest age groups , and the multicomponent programme among all children . CONCLUSION The results of this study indicate that both interventions were shown to be effective for different subgroups regarding age , gender and ethnicity . When comparing both interventions , the distribution programme was shown to be more effective , especially in increasing vegetable consumption . An important next step will be to investigate which intervention has the greatest potential to be implemented in primary schools OBJECTIVES A r and omized school based trial sought to increase fruit and vegetable consumption among children using a multicomponent approach . METHODS The intervention , conducted in 20 elementary schools in St. Paul , targeted a multiethnic group of children who were in the fourth grade in spring 1995 and the fifth grade in fall 1995 . The intervention consisted of behavioral curricula in classrooms , parental involvement , school food service changes , and industry support and involvement . Lunchroom observations and 24-hour food recalls measured food consumption . Parent telephone surveys and a health behavior question naire measured psychosocial factors . RESULTS The intervention increased lunchtime fruit consumption and combined fruit and vegetable consumption , lunchtime vegetable consumption among girls , and daily fruit consumption as well as the proportion of total daily calories attributable to fruits and vegetables . CONCLUSIONS Multicomponent school-based programs can increase fruit and vegetable consumption among children . Greater involvement of parents and more attention to increasing vegetable consumption , especially among boys , remain challenges in future intervention research This study reports the effect of a school-r and omized fruit and vegetable intervention consisting of a subscription to the Norwegian School Fruit Programme at no parental cost , and the Fruit and Vegetables Make the Marks ( FVMM ) educational programme , both delivered in the school year of 2001 - 02 . Nine r and omly chosen schools received the intervention and 10 schools served as control schools . Participating pupils completed question naires at baseline ( September 2001 ) , at Follow-up 1 ( May-June 2002 ) and at Follow-up 2 ( May 2003 ) . A total of 517 pupils ( 84 % ; mean age , 11.3 years at baseline ) participated in all three surveys . At both Follow-up 1 and Follow-up 2 , strong intervention effects were observed for all-day fruit and vegetable intake ( effect sizes were 0.6 and 0.5 portions , respectively ) . The sustained effect at Follow-up 2 , 1 year after the end of the intervention , can partly be explained by greater participation rates in the School Fruit Programme ( st and ard paid subscription ) . We conclude that the effects observed are most likely due to the no-cost subscription and not due to the FVMM educational programme , and that providing pupils with a piece of fruit or a vegetable at school at no cost for the parents is an effective strategy to increase school children 's intake of fruit and vegetables . The effect is also sustained 1 year after the end of the no-cost subscription , providing increased health benefits Background / Objectives : Previous research in the United Kingdom , where there is a school canteen system , has shown that the Food Dudes intervention substantially increases children 's fruit and vegetable consumption . The current study evaluated its effectiveness in Irel and where school meals are not provided and children bring food to school in lunchboxes . Subjects/ Methods : Participants were 4- to 11-year-old children attending two primary schools ; the schools were r and omly assigned to experimental or control conditions ( n=228 and 207 , respectively ) . During the 16-day intervention in the experimental school , children watched video adventures featuring the heroic Food Dudes , and received small rewards for eating fruit and vegetables provided . In both schools , parental provision and children 's consumption of fruit and vegetables in the lunchboxes were assessed at baseline and 12-month follow-up ( Lunchbox measures ) . Fruit and vegetables were provided in both schools over an 8-day baseline phase and the 16-day intervention , and children 's consumption was measured ( school-provided food measures ) . Results : Relative to baseline , consumption of the school-provided foods increased during the intervention in the experimental school ( P<0.001 ) , whereas in the control school it showed a significant decline . At 12-month follow-up , parents in the experimental school provided and their children consumed significantly more lunchbox fruit , vegetables and juice relative to baseline and to the control school ( P<0.001 in all instances ) . Conclusions : The Food Dudes intervention was effective in changing parental provision and children 's consumption of lunchbox fruit and vegetables in Irel and OBJECTIVE Children 's fruit/vegetable intake is still below recommended levels . This study applied Internet-tailored advice for schoolchildren and Internet-supported brief dietary counselling ( with child and parent ) within preventive health care to promote fruit/vegetable intake . SETTING /SUBJECTS The study involved 30 seventh- grade classes ( 16 in the intervention group and 14 in the control group ) with a total of 675 children aged 9 - 12 years , of whom 495 were allowed to participate . DESIGN A cluster-r and omised baseline-post-test experimental design was applied . During school hours , all children completed Internet-administered question naires on fruit/vegetable intake and related determinants . Children in the intervention group received immediate online individually tailored nutrition feedback . For each child in the intervention group , a nurse received information concerning the assessment of fruit/vegetable intake via the Internet to support a 5 min counselling protocol to promote fruit/vegetable intake . Children completed a similar post-test question naire 3 months after the first assessment . Intention-to-treat analyses were conducted using multilevel regression analyses . RESULTS A total of 486 children ( 98 % of 495 ) participated ( 263 in the intervention group , 223 in the control group ) ; 240 child-parent couples in the intervention group attended the counselling . Awareness of inadequate fruit intake ( odds ratio ( OR ) = 3.0 ; 95 % confidence interval ( CI ) = 1.8 - 5.3 ) and knowledge of recommended vegetable intake levels ( OR = 2.7 ; 95 % CI = 1.8 - 4.1 ) were significantly more likely at post-test in the intervention group than in the control group . No significant effects were found on intake or other determinants . CONCLUSIONS A compact , integrated two-component intervention can induce positive changes in knowledge and awareness of intake levels of fruit/vegetables among schoolchildren . To induce changes in intake levels , more comprehensive interventions may be needed Introduction Prevention of obesity and overweight is an important target for health promotion . Early prevention requires an intervention during childhood and adolescence . At these stages , the game could be an appropriate means to teach nutrition knowledge and to influence dietary behaviour . To this end , the authors developed Kalèdo , a new board-game . Objective The aim of the present study was to test the efficacy of Kalèdo on changes in nutrition knowledge and dietary behaviour in a pilot study conducted in three middle schools in Naples , Italy . Material s and Methods A simple two-group design ( treatment and control ) with pre- and post- assessment was employed . The classroom was the unit of recruitment and r and om assignment to groups . All students ( 307 ) in the participating schools were invited to participate . Data analysis was performed on 241 subjects . During 24 weeks , a group of 153 children from 8 classrooms ( 11–14 year old Caucasian subjects ; 78 male , 75 female ) was involved in 15–30 minute-long play sessions once a week . A question naire was given to the participants at the beginning and at the end of the study to evaluate nutrition knowledge ( 31 questions ) , physical activity ( 8 questions ) and food intake ( 34 questions ) . Anthropometric measurements were also carried out . A second group of 88 children from 5 classrooms ( same age and ethnicity ; 55 male , 33 female ) was investigated at the same times with the same question naire and anthropometric measures but they did not receive any play sessions with Kalèdo . ObservationChildren playing Kalèdo showed a significant increase in nutrition knowledge ( p<0.05 ) and in weekly vegetable intake ( p<0.01 ) with respect to the control . Conclusion The results suggest that Kalèdo could be an effective instrument to teach children about healthy diet . More research is needed to study the long term effect of this intervention OBJECTIVE To evaluate the impact of a school-based interdisciplinary health behavior intervention on diet and physical activity among children in grade s 4 and 5 . DESIGN A quasiexperimental field trial with 6 intervention and 8 matched control schools . Outcomes were assessed longitudinally using preintervention ( fall 1995 ) and follow-up ( spring 1997 ) student survey food frequency and activity measures and follow-up 24-hour recall measures of diet and activity . Change was also assessed using yearly repeated cross-sectional surveys of all grade 5 students from 1995 through 1997 . PARTICIPANTS Longitudinal data were collected from 479 students initially in grade 4 in Baltimore , Md , public schools ; 91 % were African American . Repeated 24-hour recall measures in 1997 were collected for a r and om sub sample of 336 students . Cross-sectional survey data were collected from all grade 5 students in 1995,1996 , and 1997 ( n = 2103 ) . INTERVENTION The Eat Well and Keep Moving Program was taught by classroom teachers over 2 years in math , science , language arts , and social studies classes . Material s provided links to school food services and families and provided training and wellness programs for teachers and other staff members . Intervention material s focused on decreasing consumption of foods high in total and saturated fat and increasing fruit and vegetable intake , as well as reducing television viewing and increasing physical activity . MAIN OUTCOME MEASURES Dietary intake and physical activity measured via repeated 24-hour recall were primary end points , with additional food frequency and activity measures . RESULTS The 24-hour recall measures indicated that , after controlling for baseline covariates , the percentages of total energy from fat and saturated fat were reduced among students in intervention compared with control schools ( -1.4 % ; 95 % confidence interval [ CI ] , -2.8 to -0.04 ; P = .04 and -0.60 % ; 95 % CI , -1.2 to -0.01 ; P = .05 ) . There was an increase in fruit and vegetable intake ( 0.36 servings/4184 kJ ; 95 % CI , 0.10 - 0.62 ; P=.01 ) , in vitamin C intake ( 8.8 mg/4184 kJ ; 95 % CI , 2.0 - 16 ; P=.01 ) , and in fiber consumption ( 0.7 g/4184 kJ ; 95 % CI , 0.0 - 1.4 ; P=.05 ) . Television viewing was marginally reduced ( -0.55 h/d ; 95 % CI , -1.04 to 0.04 ; P=.06 ) . Analysis of longitudinal and repeated cross-sectional food frequency data indicated similar significant decreases in the percentages of total energy from fat and saturated fat . CONCLUSION Evaluation of the Eat Well and Keep Moving Program indicates effectiveness in improving dietary intake of students and reducing television viewing OBJECTIVE This study sought to evaluate the effectiveness of a multidisciplinary elementary school-based intervention entitled Wellness , Academics & You . The primary areas of impact examined were BMI , consumption of fruits and vegetables , and physical activity . RESEARCH METHODS AND PROCEDURES The sample consisted of 1013 students in fourth and fifth grade s from 69 classes in four states . Intervention and comparison classes were r and omly selected at each school . Intervention teachers participated in workshops on the intervention and received program material s. BMI was calculated for baseline and post- data points based on measured height and weight collected by trained research teams . Baseline surveys were administered by the students ' teacher in the presence of one of the research team members and collected . RESULTS SPSS ( SPSS , Inc. , Chicago , IL ) analysis of post- data shows significant positive shifts ( p = 0.01 ) in BMI in the intervention group compared with the comparison group . Notable increases in the consumption of fruits and vegetables and increased physical activity levels were reported in the intervention group . DISCUSSION Data from this study indicate that this school-based program may contribute to the reduction of overweight and obesity . The intervention was well received by the classroom teachers and shows promise for a school-based obesity prevention initiative . This program has shown the capacity to effect positive changes in BMI through consumption of fruits and vegetables and physical activity . The evaluation covered a limited time period and , therefore , warrants additional studies to determine whether long-term program fidelity will result in continued improvement The Cafeteria Power Plus project examined whether a cafeteria-based intervention would increase the fruit and vegetable ( FV ) consumption of children . Twenty-six schools were r and omly assigned to either an intervention or control condition . Baseline lunch observations of a sample ( N = 1668 ) of first- and third- grade students occurred in the spring of 2000 ; follow-up was in the spring of 2002 . The intervention took place during two consecutive school years beginning in the fall of 2000 and consisted of daily activities ( increasing the availability , attractiveness , and encouragement for FV ) and special events ( kick-offs , samplings , challenge weeks , theater production , and finale meal ) . Training of food-service staff and cook managers was ongoing throughout the intervention phase . Students in the intervention schools significantly increased their total fruit intake . Process measures indicated that verbal encouragement by food-service staff was associated with outcomes . The outcomes suggest that multicomponent interventions are more powerful than cafeteria programs alone with this age group The " Kids Choice " school lunch program used token reinforcement , food choice , and peer participation to increase children 's fruit and vegetable consumption without later drops in food preference sometimes found in past research and often called ' overjustification effects . ' Participants included 188 school children ( 92 boys , 96 girls ; mean age = 8.0 ; 95 % Caucasian ) . After four baseline meals , children were r and omly assigned for 12 meals to receive token reinforcement for eating either fruits or vegetables . Observers recorded fruit and vegetable consumption and provided token reinforcement by punching holes into nametags each day children ate their assigned foods , then once a week children could trade these tokens for small prizes . Fruit and vegetable preference ratings were gathered with child interviews during baseline , and during follow-up conditions two weeks and seven months after the token reinforcement program . Consumption increased for fruit and for vegetables and the increases lasted throughout reinforcement conditions . Two weeks after the program , preference ratings showed increases for fruit and for vegetables . Seven months later , fruit and vegetable preferences had returned to baseline levels , suggesting the need for an ongoing school lunch program to keep preferences high , but also showing no signs of " overjustification effects " from the token reinforcement used in the " Kids Choice " school lunch program Objective : Evaluation of the impact on diet of the school fruit and vegetable scheme ( SFVS ) . Design : Non-r and omised controlled trial . Setting : Infant and primary schools in the north of Engl and . Participants : 3703 children aged four to six years ( reception , year 1 , and year 2 ) . Intervention : One portion of fruit or vegetable provided per child on each school day between February and December 2004 . Main outcome measures : Fruit and vegetables consumed and intake of nutrients . Results : The SFVS was associated with an increase in fruit intake across reception and year 1 pupils of 0.4 portions ( 95 % confidence interval , 0.2 to 0.5 ) and 0.6 portions ( 0.4 to 0.9 ) , respectively , at three months , which fell to 0.2 ( 0.1 to 0.4 ) and 0.3 ( 0.1 to 0.6 ) at seven months . In year 2 it was associated with an increase of 0.5 portions ( 0.2 to 0.7 ) of fruit at three months , which fell to baseline values at seven months when these children were no longer eligible for the scheme . Overall , at seven months there were no changes in vegetable consumption , no associations between the SFVS and energy , fat , or salt intake , and small changes in carotene and vitamin C intake . Conclusions : The SFVS promoted an increase in fruit intake after three months . At seven months the effect remained significant but reduced , and it returned to baseline in year 2 when pupils were no longer part of the scheme . There was a small impact on the intake of some nutrients across the children surveyed The objective of the present study was to evaluate the effects of the Pro Children intervention on schoolchildren 's fruit and vegetable ( FV ) intake after 1 and 2 years of follow-up . The intervention combined a FV curriculum with efforts to improve FV availability at schools and at home . Effects were examined in a group-r and omised trial among 1,472 10 - 11-year-old children from sixty-two schools in Norway , the Netherl and s and Spain . FV intake was assessed by means of vali date d self-administered question naires completed before the intervention ( September 2003 ) , immediately after the first year of the intervention ( May 2004 ) and 1 year later ( May 2005 ) . Data were analysed using multilevel linear regression analyses with age and sex as covariates . Significant intervention effects for FV intake were found at first follow-up in the total sample . The adjusted FV intake reported by the children from intervention schools was 20 % higher than FV intake reported by children from control schools . At 1 year later , a significant impact was only observed in Norway . Positive intervention effects on FV intake occurred both at school and outside school . We conclude that the Pro Children intervention is a promising means to promote European schoolchildren 's FV intakes , but mainly fruit intake , in the short term . As shown in Norway , where the intervention was best implemented , the intervention might also result in longer-term effects . Further strategies need to be developed that can improve implementation , have an impact on vegetable intake and can secure sustained effects A theory-based multicomponent intervention ( Gimme 5 ) was design ed and implemented to impact fourth- and fifth- grade children ’s fruit , juice , and vegetable ( FJV ) consumption and related psychosocial variables . Gimme 5 was a r and omized controlled intervention trial with school ( n = 16 elementary ) as unit of r and om assignment and analysis . Participants included the cohort of students who were in the third grade in the winter of 1994 and students who joined them in the fourth and fifth grade s. The intervention included a curriculum , newsletters , videotapes , and point-of-purchase education . Evaluation included 7-day food records and psychosocial measures from students , telephone interviews with parents , and observational assessment s. Favorable results were observed for consumption of FJV combined , FJV consumed at weekday lunch , eating FJV self-efficacy , social norms , asking behaviors , and knowledge . A theory-based school nutrition education program can help change children ’s FJV consumption and impact factors at home that predispose to FJV consumption , but changes were small , and their persistence is unknown BACKGROUND Fruit , juice , and vegetable ( FJV ) consumption among children is low . Innovative programs are needed to enable children to increase FJV intake . Psychoeducational multimedia permits the delivery of interventions as design ed and capitalizes on known behavior change principles . DESIGN Elementary school was the unit of recruitment , assignment , and analysis . Twenty-six elementary schools were pair matched on size and percentage of free or reduced-price lunch , and r and omly assigned to treatment or control groups . Data were collected just before and just after the program . SETTING / PARTICIPANTS All fourth- grade students in participating elementary schools were invited to participate . Data were collected on 1578 students . MAIN OUTCOME Servings of fruit , 100 % juice , and vegetables consumed . INTERVENTION Squire 's Quest ! is a ten-session , psychoeducational , multimedia game delivered over 5 weeks , with each session lasting about 25 minutes . Based on social cognitive theory , educational activities attempted to increase preferences for FJV through multiple exposures and associating fun with their consumption , increase asking behaviors for FJV at home and while eating out , and increase skills in FJV preparation through making virtual recipes . MEASURES Four days of dietary intake were assessed before and after the intervention . Assessment was made by the Food Intake Recording Software System ( FIRSSt ) , which conducts a multiple pass , 24-hour dietary intake interview directly with the children . RESULTS Children participating in Squire 's Quest ! increased their FJV consumption by 1.0 servings more than the children not receiving the program . CONCLUSIONS Psychoeducational multimedia games have the potential to substantially change dietary behavior . More research is warranted The object of this study was to determine whether students attending schools with self-service salad bars consume a greater amount of fruits and vegetables compared with students using preportioned servings and to evaluate the relationship between number of items offered and fruit and vegetable consumption . Two hundred ninety-four students in first through fifth grade were r and omly selected from two schools with salad bars and two with preportioned servings . Weights of fruit and vegetable items were measured pre- and postconsumption and interobserver agreement + /-1 g was > or = 95 % . Presence of a salad bar was not associated with greater fruit and vegetable consumption . Fruit and vegetable consumption was positively related to the number of fruit and vegetable items offered at salad bars ( P < .05 ) , adjusting for sex and grade . Fruit and vegetable variety was associated with elementary school-age children 's fruit and vegetable consumption when using salad bars R and omised controlled trials are widely accepted as the most reliable method of determining effectiveness , but most trials have evaluated the effects of a single intervention such as a drug . Recognition is increasing that other , non-pharmacological interventions should also be rigorously evaluated.1 - 3 This paper examines the design and execution of research required to address the additional problems result ing from evaluation of complex interventions —that is , those “ made up of various interconnecting parts.”4 The issues dealt with are discussed in a longer Medical Research Council paper ( www.mrc.ac.uk/complex_packages.html ) . We focus on r and omised trials but believe that this approach could be adapted to other design s when they are more appropriate . # # # # Summary points Complex interventions are those that include several components The evaluation of complex interventions is difficult because of problems of developing , identifying , documenting , and reproducing the intervention A phased approach to the development and evaluation of complex interventions is proposed to help research ers define clearly where they are in the research process Evaluation of complex interventions requires use of qualitative and quantitative evidence There are specific difficulties in defining , developing , documenting , and reproducing complex interventions that are subject to more variation than a drug . A typical example would be the design of a trial to evaluate the benefits of specialist stroke units . Such a trial would have to consider the expertise of various health professionals as well as investigations , drugs , treatment guidelines , and arrangements for discharge and follow up . Stroke units may also vary in terms of organisation , management , and skill mix . The active components of the stroke unit may be difficult to specify , making it difficult to replicate the intervention . The box gives other examples of complex interventions . # # # # Examples of complex interventions Service delivery and organisation : Stroke units Hospital at home Interventions directed at health professionals ' behaviour : Strategies for implementing guidelines Computerised decision support Community interventions : Community |
13,834 | 26,001,751 | Conclusion Postoperative recovery was significantly faster after desflurane than after sevoflurane , isoflurane , or propofol anesthesia in obese patients .
No clinical ly relevant differences were observed regarding PACU discharge time , incidence of PONV , or postoperative pain scores .
Conclusion La récupération postopératoire a été significativement plus rapide après desflurane qu’après une anesthésie par sévoflurane , isoflurane ou propofol chez des patients obèses .
Aucune différence cliniquement pertinente n’a été observée concernant les délais de congé de la salle de réveil , l’incidence des nausées et vomissements postopératoires , ou des scores de douleur postopératoire . | Purpose Obese patients present a challenge to safe general anesthesia because of impaired cardiopulmonary physiology and increased risks of aspiration and acute upper airway obstruction .
Since studies are lacking regarding the postoperative effects on recovery from general anesthesia in morbidly obese patients , we conducted a systematic review and meta- analysis of recovery outcomes in morbidly obese patients who had undergone general anesthesia .
The systematic review was registered with PROSPERO (CRD42014009480).RésuméObjectifLes patients obèses constituent un défi pour une anesthésie générale sécuritaire en raison d’une physiologie cardiopulmonaire altérée et de risques accrus d’aspiration et d’obstruction aiguë des voies aériennes hautes . | We compared postoperative recovery after desflurane ( n = 25 ) versus sevoflurane ( n = 25 ) anesthesia in morbidly obese adults ( body mass index ≥35 ) who underwent gastrointestinal bypass surgery via an open laparotomy . After premedication with midazolam and metoclopramide 1 h before surgery , epidural catheter placement , induction of anesthesia with fentanyl and propofol , and tracheal intubation facilitated with succinylcholine , anesthesia was maintained with age-adjusted 1 minimum alveolar concentration ( MAC ) desflurane or sevoflurane . Fentanyl IV , morphine or local anesthetics epidurally , and vasoactive drugs as needed were used to maintain arterial blood pressure at ±20 % of baseline value and to keep bispectral index of the electroencephalogram values between 40 to 60 U. Although patients were anesthetized with desflurane for a longer time ( 261 ± 50 min versus 234 ± 37 min , mean ± sd ; P < 0.05 , desflurane versus sevoflurane , respectively ) and for more MAC-hours ( 4.2 ± 0.9 h versus 3.7 ± 0.8 h ; P < 0.05 ) , significantly earlier recovery of response to comm and and tracheal extubation occurred in patients given desflurane than in patients given sevoflurane . The modified Aldrete score was greater in desflurane-anesthetized patients on admission to the postanesthesia care unit ( PACU ) ( P = 0.01 ) but not at discharge ( P = 0.47 ) . On admission to PACU , patients given desflurane had higher oxygen saturations ( 97.0 % ± 2.4 % ) than patients given sevoflurane ( 94.8 % ± 4.4 % , P = 0.035 ) . Overall , the incidence of postoperative nausea and vomiting and the use of antiemetics did not differ between the two anesthetic groups . We conclude that morbidly obese adult patients who underwent major abdominal surgery in a prospect i ve , r and omized study awoke significantly faster after desflurane than after sevoflurane anesthesia and the patients anesthetized with desflurane had higher oxygen saturation on entry to the PACU Background Previous studies have noted a high incidence of adverse outcomes in the postanesthesia care unit ( PACU ) , but few have examined associated factors and patient outcomes . To determine the frequency of acute , unanticipated respiratory problems and to examine the associated patient , surgical , and anesthetic factors , we prospect ively collected preoperative , intraoperative , and postoperative data on 24,157 consecutive PACU patients who received a general anesthetic during a 33-month period . Methods A PACU critical respiratory event ( CRE ) , was defined as any unanticipated hypoxemia ( hemoglobin oxygen saturation < 90 % ) , hypoventilation ( respiratory rate < 8 breaths/min or arterial carbon dioxide tension > 50 mmHg ) or upper-airway obstruction ( stridor or laryngospasm ) requiring an active and specific intervention ( ventilation , tracheal intubation , opioid or muscle relaxant antagonism , insertion of oral/nasal airway or airway manipulation ) . These problems were documented by PACU nurses whereas data on case-mix , surgical factors , and intraoperative management were retrieved from the anesthetic record . Significant patient , surgical , and anesthetic factors were identified by logistic regression analysis . Other morbidity experienced by patients with a CRE was also noted . Results For patients given general anesthesia the risk of a CRE was 1.3 % ( hypoxemia 0.9 % , hypoventilation 0.2 % , airway obstruction 0.2 % ) . Preoperative factors that increase risk were age > 60 yr , male gender , diabetes , and obesity ( P < 0.05 ) . Patients who underwent operative procedures on an emergency basis and whose operation was longer than 4 h were also at increased risk , but those undergoing perineal procedures were at lower risk ( P < 0.05 ) . Anesthetic risk factors ( P < 0.05 ) included opioid premedication ( relative odds 1.8 ) , sedatives preoperatively ( 2.0 ) , fentanyl > 2.0 μg.kg–1.h–1 as the sole opioid ( 1.9 ) , fentanyl used in combination with morphine ( 1.6 ) and atracurium ≥ 0.25 mg.kg–1.h–1 ( 2.2 ) . Patients in whom anesthesia was induced with thiopental ( relative odds 2.5 ) , compared with those who received propofol for induction , were also at increased risk of a CRE . Patients with a CRE stayed longer in PACU , had higher rates of unanticipated admissions to the intensive care unit and were more likely to have PACU cardiac problems ( P < 0.01 ) . Conclusions A CRE is relatively rare . Multiple patient and surgical factors and specific aspects of anesthetic management are associated with the occurrence of a CRE in the PACU Background : The choice of anesthetic technique for general anesthesia in morbidly obese patients remains controversial . We aim ed to compare blood gases , recovery and hemodynamic parameters using TIVA and sevoflurane anesthesia in bariatric surgery . Methods : The study was performed with permission of the ethics committee . We studied 40 morbidly obese patients allocated to 2 groups . The total I.V. anesthesia ( TIVA ) group was named Group T , and the sevoflurane group was named Group S. In Group T , anesthesia induction was achieved with propofol . In Group S , anesthesia induction was achieved by sevoflurane with single breath technique , with maintenance provided with 1 - 2 % volume sevoflurane . Student t , Chi square and ANOVA tests were used for data analysis ; p-value < 0.05 was considered statistically significant . Results : There was no significant difference between the 2 groups in demographic data , blood gas values and recovery characteristic . Hemodynamic values were significantly lower in Group T than Group S , during and after the operative period . Conclusion : While sevoflurane induction and maintenance is a suitable anesthetic modality for obese patients , TIVA can be applied easily in those patients possessing no extra risk factors other than morbid obesity STUDY OBJECTIVE To determine if desflurane results in a faster emergence as measured by time to eye opening compared to sevoflurane in morbidly obese patients undergoing laparoscopic gastroplasty . STUDY DESIGN Prospect i ve , r and omized , double-blinded study . SETTING Tertiary care hospital . PATIENTS 70 patients with a body mass index of 35 or higher undergoing laparoscopic gastroplasty . INTERVENTIONS Patients were r and omized into two groups to receive either desflurane or sevoflurane for maintenance of general anesthesia . MEASUREMENTS Intraoperative measured variables included the time from when the inhalation agent was turned off ( no agent delivered ) to eye opening and the time from when the inhalation agent was turned off to extubation . Postanesthesia care unit (PACU)-measured variables on admission and at 15 minute intervals until discharge included oxygen saturation ( Spo2 ) , blood pressure , heart rate , pain and nausea Visual Analog Scale ( VAS ) scores , emesis , modified Aldrete score , and Mini-Mental Status ( MMS ) examination score . MAIN RESULTS No differences were noted in demographic data , total surgical operative time , times from turning inhalation agent off to eye opening and extubation , or average length of stay in PACU . No differences were noted with respect to pain VAS , treatment for pain , modified Aldrete scores , emesis , or treatment for postoperative nausea or emesis . Differences were noted in PACU nausea VAS at 15 minutes , PACU nausea VAS at discharge , and PACU-MMS score at 45 minutes ; however , multivariate analysis of variance revealed no differences between groups over the repeated PACU measured time periods in nausea VAS ( P=0.17 ) or in MMS ( P=0.34 ) . Higher heart rates in the desflurane group were observed during PACU admission ( 82.3+/-9.8 vs 74.4+/-13.4 bpm , P<0.01 ) and 15 minutes post PACU admission ( 79.4+/-12.1 vs 71.3+/-13.2 bpm , P=0.01 ) . CONCLUSIONS In morbidly obese patients undergoing laparoscopic gastroplasty , emergence , as measured by time to eye opening , did not differ between desflurane and sevoflurane , with similar recovery characteristics Context : Morbidly obese patients are prone for intraoperative hemodynamic disturbances and postoperative airway complications . Aim : Comparison of intraoperative hemodynamics and postoperative recovery characteristics of desflurane versus sevoflurane in morbidly obese patients undergoing laparoscopic bariatric surgery . Setting s and Design : R and omized controlled trial Material s and Methods : After institutional ethics committee approval and written informed consent , 40 morbidly obese patients ( BMI > 35 kg/m2 ) were r and omized to receive desflurane or sevoflurane as part of a st and ardized general anesthesia technique . Volatile anesthetic concentration was titrated to maintain electroencephalographic bispectral index score ( BIS ) in the range of 40 - 60 . Mean arterial pressure ( MAP ) and heart rate ( HR ) were recorded preoperatively , at induction and intubation , then at regular intervals . After extubation , early recovery was recorded by time to emergence and orientation to time and place . In post anesthesia care unit , intermediate recovery was assessed by modified Aldrete Score and Digit Symbol Substitution Test ( DSST ) . Results : Intraoperative MAP and HR did not differ between the two groups ( P > 0.05 ) . The time to response to painful stimuli , obeying verbal comm and s and spontaneous eye opening was shorter ( P = 0.001 ) and modified Aldrete Score was higher after desflurane anesthesia than after sevoflurane anesthesia ( P = 0.049 ) . DSST also returned towards normal faster after desflurane ( 28.50 ± 6.30 min vs. 35.0 ± 5.62 min , P = 0.03 ) . Conclusions : Both desflurane and sevoflurane produce similar hemodynamic changes but the immediate and intermediate recovery was significantly faster after desflurane thus contributing to fast tracking and early discharge of patients STUDY OBJECTIVE Morbid obesity is associated with significant comorbidities . Desflurane has a low fat-blood solubility coefficient and may be better suited in this population to achieve a rapid emergence ; however , sevoflurane has favorable cardiorespiratory properties that might also prove advantageous in the morbidly obese ( MO ) patient . This study used careful drug titration to determine if emergence differences between sevoflurane and desflurane could be minimized in MO patients . DESIGN A r and omized , prospect i ve blinded study to determine the emergence profiles of desflurane and sevoflurane in MO patients when anesthetic drug titration is used . SETTING Operating room of the VA Medical Center , Milwaukee , Wis. PATIENTS Forty American Society of Anesthesiologists II and III , MO patients ( body mass index > or = 35 kg/m2 ) , who were scheduled for elective surgery predicted to last for more than 2 hours , were studied . INTERVENTIONS Patients were induced with fentanyl , midazolam , and propofol and maintained with desflurane or sevoflurane , mixed in air and oxygen . Intraoperative bispectral index ( BIS ) was targeted to 45 to 50 and to 60 in the last 15 minutes of surgery . MEASUREMENTS Intraoperative anesthetic concentration , BIS , and hemodynamics were recorded . During emergence , time to follow comm and and extubation were noted , with assessment s of cognitive function via the Mini-Mental Status Test and psychomotor performance via the Digit Symbol Substitution Test . A blinded observer recorded key recovery events . MAIN RESULTS Demographic data ( age , 61 [ 36 - 83 ] years ; body mass index , 38 [ 35 - 47 ] kg/m2 ) , surgical procedures , length of anesthesia ( approximately 3.5 hours ) , adjuvant drugs , and intraoperative BIS , heart rate , and mean arterial pressure were not significantly different . Hemodynamics , time to follow comm and s and to extubation , and results of Digit Symbol Substitution Test and Mini-Mental Status Test did not differ between anesthetic groups during recovery . CONCLUSIONS There were no differences in emergence and recovery profiles in MO patients receiving desflurane or sevoflurane when anesthetic concentration was carefully titrated BACKGROUND : In this study , we evaluated the influence of propofol versus desflurane anesthesia in overweight patients on postoperative lung function and pulse oximetry values . METHODS : We prospect ively studied 134 patients with body mass indices of 25 to 35 kg/m2 undergoing minor peripheral surgery lasting 40 to 120 minutes . Patients were r and omly assigned to receive propofol ( total IV anesthesia ) or desflurane anesthesia via a tracheal tube targeting bispectral index values of 40 to 60 . Premedication , adjuvant drug usage , and ventilation were st and ardized . We measured oxyhemoglobin saturation and lung function preoperatively ( baseline ) , and at 10 minutes , 0.5 hour , 2 hours , and 24 hours after tracheal extubation . All values were measured with the patient supine , in a 30 ° head-up position . Changes from preoperative baseline values were first analyzed for the impact of body mass index and type of anesthesia using univariate methods , followed by linear regression and multivariate analysis of variance . RESULTS : Within the first 2 hours after surgery , the propofol group displayed lower oxyhemoglobin saturation ( at 2 hours , mean ± SD , 93.8 % ± 2.0 % vs 94.6 % ± 2.1 % ; P < 0.007 ) and lung function ( forced vital capacity , forced expiratory volume exhaled in 1 second [ FEV1 ] , peak expiratory flow , midexpiratory flow [ MEF ] , forced inspiratory vital capacity , and peak inspiratory flow ; between 11 % and 20 % larger reduction from baseline in the propofol group , all P < 0.001 ) compared with the desflurane group . Even 24 hours after surgery , FEV1 , peak expiratory flow , MEF , forced inspiratory vital capacity , and peak inspiratory flow were reduced more in the propofol group ( all P < 0.01 ) . At 2 hours after extubation , increasing obesity was associated with decreasing FEV1 and MEF in patients anesthetized with propofol but not desflurane ( P < 0.01 ) . CONCLUSION : We conclude that , for superficial surgical procedures of up to 120 minutes , maintenance of anesthesia with propofol impairs early postoperative lung function and pulse oximetry values more than with desflurane . Furthermore , increasing obesity decreases pulmonary function at 2 hours after propofol anesthesia but not after desflurane anesthesia Recovery from anesthesia might be compromised in obese patients . Because of its pharmacological properties , desflurane might allow rapid postoperative recovery for these patients . We compared postoperative recovery for 36 obese patients r and omized to receive either desflurane , propofol , or isoflurane to maintain anesthesia during laparoscopic gastroplasties . Anesthesia was induced with propofol and succinylcholine IV and was maintained with rocuronium , alfentanil , inhaled nitrous oxide , and the study drug . Immediate recovery ( i.e. , times from the discontinuation of anesthesia to tracheal extubation , eye opening , and the ability to state one ’s name ) was measured . At the time of postanesthesia care unit ( PACU ) admission , arterial saturation and the ability of patients to move were recorded . In the PACU , intermediate recovery was measured by using sedation and psychometric evaluations , 30 , 60 , and 120 min postoperatively . Data were compared between groups by using the Kruskal-Wallis and & khgr;2 tests . Results were reported as means ± sd . P < 0.05 , compared with desflurane , was considered significant . Immediate recovery occurred faster , and was more consistent , after desflurane than after propofol or isoflurane ( times to extubation were 6 ± 1 min , 13 ± 8 min [ P < 0.05 , compared with desflurane ] , and 12 ± 6 min [ P < 0.05 , compared with desflurane ] , respectively ) . At PACU admission , Spo2 values were significantly higher and patient mobility was significantly better after desflurane than after isoflurane or propofol . Sedation was significantly less pronounced with desflurane at 30 and 120 min postoperatively . In morbidly obese patients , postoperative immediate and intermediate recoveries are more rapid after desflurane than after propofol or isoflurane anesthesia . This advantage of desflurane persists at least for 2 h after surgery and is associated with both an improvement in patient mobility and a reduced incidence of postoperative desaturation . Implication s In morbidly obese patients , postoperative immediate and intermediate recoveries are more rapid and consistent after desflurane than after propofol or isoflurane anesthesia BACKGROUND The concept of an ' inhalation bolus ' can be used to optimize inhaled drug administration . We investigated the depth of anaesthesia , haemodynamic stability , and recovery time in morbidly obese patients result ing from bispectral index (BIS)-guided sevoflurane or desflurane administration and BIS-triggered inhalation boluses of sevoflurane or desflurane combined with titration of remifentanil . METHODS Fifty morbidly obese patients undergoing laparoscopic gastroplasty received either BIS-guided sevoflurane or desflurane anaesthesia in combination with a remifentanil target-controlled infusion . Intraoperative haemodynamic stability and BIS control were measured . Immediate recovery was recorded . RESULTS Intraoperatively , the BIS was between 40 and 60 for a greater percentage of time in the sevoflurane ( 78 (13)% of case time ) than in the desflurane patients ( 64 (14)% of case time ) , owing to too profound anaesthesia in the desflurane patients at the start of the procedure . However , fewer episodes of hypotension were found in the desflurane group , without the occurrence of more hypertensive episodes . During immediate recovery , eye opening , extubation , airway maintenance , and orientation occurred sooner in the desflurane group . CONCLUSIONS Immediate recovery was significantly faster in the desflurane group . Overall hypnotic controllability measured by BIS was less accurate with desflurane . Overall haemodynamic controllability was better when using desflurane . Fewer episodes of hypotension were found in the desflurane group . The use of the inhalation bolus was found to be appropriate in both groups without causing severe haemodynamic side effects . Minimal BIS values were significantly lower after a desflurane bolus BACKGROUND The aim of this study was to compare desflurane vs sevoflurane kinetics and dynamics in morbidly obese patients and their recovery profile when no premedication had been used . METHODS Twenty-eight unpremedicated obese patients were r and omly allocated to receive either sevoflurane ( n = 14 ) or desflurane ( n = 14 ) as the main anaesthetic agent . After induction of anaesthesia , either sevoflurane 2 % or desflurane 6 % was administered for 30 min via a non-rebreathing circuit . The kinetics of sevoflurane and desflurane were determined by measuring and recording end-tidal sample s during this time . The bispectral index was used to indicate the level of hypnosis . At the end of the procedure , the end-tidal concentrations of sevoflurane and desflurane were recorded during the first 5 min after stopping their administration . Time from discontinuation of the anaesthetic drugs to eye opening on verbal comm and , squeezing the observer 's h and on comm and , extubation , stating their name , giving their correct date of birth , discharge from the recovery room , and duration of the surgery and anaesthesia were also recorded . RESULTS The F(A)/F(I ) ratio was significantly higher in the desflurane group from the 15th to the 30th min . The wash-out phase was faster for desflurane during the total observation period . When desflurane was used , recovery was also faster . CONCLUSIONS Desflurane provides faster wash-in and wash-out than sevoflurane in morbidly obese patients , and recovery is much faster after desflurane administration when no premedication has been used STUDY OBJECTIVE To compare the efficacy and recovery profile of sevoflurane and isoflurane as the main anesthetics for morbidly obese patients . DESIGN R and omized , blinded study . SETTING In patients . PATIENTS 30 ASA physical status II and III obese patients [ body mass index ( BMI ) > 35 kg/m(2 ) ] undergoing laparoscopic gastric b and ing for morbid obesity . INTERVENTIONS After st and ard intravenous induction of general anesthesia and tracheal intubation , anesthesia was maintained with either sevoflurane or isoflurane as the main anesthetics . The end-tidal concentrations of the volatile drugs were adjusted to maintain systolic arterial blood pressure within + /-20 % from baseline values . When the surgeon started the skin suture , the end-tidal concentration of the inhalational drug was reduced to 0.5 minimum alveolar concentration in both groups . At the last skin suture , the inhalational drug was discontinued and the vaporizator was removed to allow blinded evaluation of the emergence times . MEASUREMENTS AND MAIN RESULTS No differences in anesthetic exposure , hemodynamic parameters , incidence of untoward events , or postoperative pain relief were reported between the two groups . Extubation , emergence , and response times were shorter after sevoflurane [ 6 min ( 3 - 15 min ) , 8 min ( 5 - 18 min ) , and 12 ( 6 - 25 min ) ] than isoflurane [ 10 min ( 6 - 26 min ) , 14 min ( 6 - 21 min ) , and 21 min ( 14 - 41 min ) ] ( p = 0.001 , p = 0.03 , and p = 0.0005 , respectively ) . The median time for postanesthesia care unit discharge was 15 minutes ( 25th-75th percentiles : 10 - 18 min ) after sevoflurane and 27 minutes ( 25th-75th percentiles : 20 - 30 min ) after isoflurane ( p = 0.0005 ) . CONCLUSIONS Sevoflurane provides a safe and effective intraoperative control of cardiovascular homeostasis in morbidly obese patients undergoing laparoscopic gastric b and ing , with the advantage of a faster recovery and earlier discharge from the postanesthesia care unit than isoflurane This study was design ed to test the hypothesis that using the less soluble volatile anesthetics , desflurane and sevoflurane , as alternatives to propofol for maintenance of anesthesia facilitates the ability of out patients to achieve postanesthesia care unit ( PACU ) discharge criteria ( i.e. , fast-track eligibility ) on arrival in the PACU after laparoscopic surgery . One hundred-twenty consenting women undergoing laparoscopic tubal ligation procedures were r and omly assigned to one of three treatment groups . After a st and ardized induction of anesthesia and tracheal intubation sequence , anesthesia was maintained with either desflurane 2%-6 % , sevoflurane 0.6%-1.75 % , or propofol 50 - 150 micro g [ center dot ] kg-1 [ center dot ] min-1 in combination with nitrous oxide 60 % in oxygen . Recovery times , postanesthesia recovery scores , and the number and type of therapeutic interventions in the PACU were recorded . Compared with the propofol group , the times to awakening and to achieve a recovery score of 10 were significantly shorter , and the percentage of patients judged fast-track eligible on arrival in the PACU was significantly higher , in the desflurane and sevoflurane groups ( 90 % and 75 % vs 26 % ) . In conclusion , compared with propofol , the use of desflurane and sevoflurane for the maintenance of general anesthesia result ed in a higher percentage of patients being judged fast-track eligible after outpatient laparoscopic tubal ligation procedures . Implication s : Bypassing the recovery room by transferring out patients directly to the step-down unit after ambulatory surgery ( " fast-tracking " ) could result in significant cost-savings . We examined the effects of three different maintenance anesthetics-desflurane , sevoflurane , and propofol-on the fast-track eligibility of out patients after laparoscopic tubal ligation surgery . Compared with propofol , desflurane and sevoflurane result ed in a higher percentage of out patients being judged eligible for fast-tracking . ( Anesth Analg 1998;86:267 - 73 Background : This r and omized prospect i ve study with blinded postanesthesia care unit ( PACU ) observers compared the recovery profiles in morbidly obese patients who received sevoflurane or desflurane for maintenance of anesthesia in combination with a remifentanil target controlled infusion ( TCI ) . Methods : 50 morbidly obese patients scheduled for laparoscopic gastric b and ing were included to receive BIS-guided sevoflurane or desflurane anesthesia with BIS-triggered inhalation boli in combination with remifentanil TCI . In the PACU , the following recovery scores were investigated : Modified Aldrete score , a modified Observers ' Assessment of Alertness/Sedation Scale ( OAA/S ) , pain numerical rating scale ( NRS ) , oxygen saturation ( SpO2 ) and postoperative nausea and vomiting ( PONV ) . Results : OAA/S and NRS pain scores showed a similar evolution in both groups from the moment of PACU admission up to 120 minutes after admission . In both groups , patients showed no serious hypoxemia during PACU stay . Incidence of PONV was shorter lasting in the sevoflurane group compared to the desflurane group . Conclusions : No clinical ly relevant difference was found in recovery in the PACU between morbidly obese patients anesthetized with desflurane or sevoflurane . Both agents result ed in satisfactory recovery in morbidly obese patients BACKGROUND The solubility of desflurane compared with sevoflurane suggests more rapid recovery from desflurane anaesthesia . This could be important after prolonged anaesthesia and fast recovery may be advantageous in the elderly where slow recovery of mental function is a concern . We compared emergence from desflurane vs sevoflurane in elderly patients undergoing two or more hours of anaesthesia . METHODS Fifty ASA physical status I , II , or III patients , 65 yr of age or older , undergoing anaesthesia expected to last two or more hours were r and omly assigned to receive desflurane/nitrous oxide or sevoflurane/nitrous oxide anaesthesia . Patients were given 1 - 2 microg x kg(-1 ) fentanyl i.v . and anaesthesia was induced with propofol 1.5 - 2.5 mg x kg(-1 ) i.v . and maintained with either desflurane 2 - 6 % or sevoflurane 0.6 - 1.75 % with nitrous oxide 65 % in oxygen . Inspired anaesthetic concentrations were adjusted to obtain adequate surgical anaesthesia and to maintain mean arterial pressure within 20 % of baseline values . Early and intermediate recovery times were recorded . Digit-Symbol Substitution Test ( DSST ) scores and Visual Analog Scale ( VAS ) scores for pain and nausea were recorded before pre-medication and every 15 min in the Post Anaesthesia Care Unit ( PACU ) until patients were discharged . RESULTS Early recovery times are given as median , quartiles . The times to extubation ( 5 ( 4 - 9 ) ; 9 ( 5 - 13 ) min ) , eye opening ( 5 ( 3 - 5 ) ; 11 ( 8 - 16 ) min ) , squeezing fingers on comm and ( 7 ( 4 - 9 ) ; 12 ( 8 - 17 ) min ) ; and orientation ( 7 ( 5 - 9 ) ; 16 ( 10 - 21 ) min ) were significantly less ( P<0.05 ) for desflurane than for sevoflurane . Intermediate recovery , as measured by the DSST and time to ready for discharge from the PACU ( 56 ( 35 - 81 ) ; 71 ( 61 - 81 ) min ) was similar in the two groups . CONCLUSIONS Early but not intermediate recovery times of elderly patients undergoing a wide range of surgical procedures requiring two or more hours of anaesthesia is significantly ( P < or=0.05 ) faster after desflurane Specific postoperative outcomes were assessed in 67 morbidly obese subjects who received general anesthesia for gastric stapling . Each patient was r and omly assigned to receive N2O;O2 combined with fentanyl ( n = 20 ) , enlurane ( n = 24 ) , or halothane ( n = 23 ) . Time from last skin stitch until the patient opened eyes on comm and was significantly less for the fentanyl group ( 3.0 ± 0.7 min ) than for the enflurane group ( 13.2 ± 1.9 min ) or the halothane group ( 17.4 ± 2.9 min ) with P < 0.05 . However , no significant differences in time from last skin stitch to extubation were noted among the fentanyl ( 16.2 ± 7.4 min ) , enflurane(15.2 ± 1.6 min ) , and halothane ( 21.6 ± 5.8 min ) groups ( P > 0.05 ) . Recovery room ( RR ) admission temperatures were similar for the three groups : fentanyl , 36.1 ± 0.1 ° C ; enflurane , 35.7 ± 0.2 ° C ; and halothane , 36.0 ± 0.1 ° C ( P > 0.05 ) . Total RR time was not significantly different : fentanyl , 108 ± 6 min , enflurane , 118 ± 4 min ; and halothane , 112 ± 10 min ( P > 0.05 ) . In addition , no difference in RR and 24-hour postoperative narcotic ( meperidine ) requirements was demonstrated among the anesthetic groups . These data suggest that increased lipid solubility of volatile anesthetics ( halothane or enflurane ) produces neither delayed awakening nor prolonged recovery time in morbidly obese subjects . Considering the early ( 24 hour ) postoperative outcomes studied , there is little to commend one general anesthetic technique over another in the obese subset of the population Backgroud Sevoflurane has a lower blood : gas partition coefficient than isoflurane , which may cause a more rapid recovery from anesthesia ; it also might cause faster emergence times than for propofol‐based anesthesia . We evaluated a data base that included recovery endpoints from controlled , r and omized , prospect i ve studies sponsored by Abbott Laboratories that compared sevoflurane to isoflurane or propofol when extubation was planned immediately after completion of elective surgery in adult patients . Methods Sevoflurane was compared to isoflurane in eight studies ( N = 2,008 ) and to propofol in three studies ( N = 436 ) . Analysis of variance was applied using least squares method mean values to calculate the pooled mean difference in recovery endpoints between primary anesthetics . The effects of patient age and case duration also were determined . Results Sevoflurane result ed in statistically significant shorter times to emergence ( ‐3.3 min ) , response to comm and ( ‐3.1 min ) , orientation ( ‐4.0 min ) and first analgesic ( ‐8.9 min ) but not time to eligibility for discharge ( ‐1.7 min ) compared to isoflurane ( mean difference ) . Times to recovery endpoints increased with increasing case duration with isoflurane but not with sevoflurane ( patients receiving isoflurane took 4‐5 min more to emerge and respond to comm and s and 8.6 min more to achieve orientation during cases longer than 3 hr in duration than those receiving sevoflurane ) . Patients older than 65 yr had longer times to orientation , but within any age group , orientation was always faster after sevoflurane . There were no differences in recovery times between sevoflurane and propofol . Conclusions Recovery from sevoflurane was 3‐4 min faster than with isoflurane in all age groups , and the difference was magnified in longer‐ duration surgical cases ( > 3 hr ) |
13,835 | 27,589,694 | Subgroup analysis by method of nerve location showed that the effect size was greater when neurostimulation was used rather than the transarterial technique .
Otherwise there were no statistically significant differences between groups in any of the three comparisons on secondary analgesia failure , complications and patient discomfort .
AUTHORS ' CONCLUSIONS This review provides evidence that multiple-injection techniques using nerve stimulation for axillary plexus block produce more effective anaesthesia than either double or single-injection techniques .
However , there was insufficient evidence to draw any definitive conclusions regarding differences in other outcomes , including safety | BACKGROUND Regional anaesthesia comprising axillary block of the brachial plexus is a common anaesthetic technique for distal upper limb surgery .
This is an up date of a review first published in 2006 and previously up date d in 2011 and 2013 .
OBJECTIVES To compare the relative effects ( benefits and harms ) of three injection techniques ( single , double and multiple ) of axillary block of the brachial plexus for distal upper extremity surgery .
We considered these effects primarily in terms of anaesthetic effectiveness ; the complication rate ( neurological and vascular ) ; and pain and discomfort caused by performance of the block . | BACKGROUND AND OBJECTIVES High-dose transarterial technique results in highly effective axillary block . The multiple nerve stimulation technique ( MNS ) requires more time and experience . This prospect i ve study aim ed at comparing onset and success rate of multiple-injection axillary brachial plexus block using two methods of nerve location : transarterial or multiple nerve stimulation technique . METHODS Axillary block was initially induced with 800 mg lidocaine with epinephrine . The transarterial group received deeply injected 30 mL of 1.6 % lidocaine with epinephrine , and 20 mL superficially to the axillary artery . For the multiple nerve stimulation group , three terminal motor nerves were electrolocated and blocked with 20 mL , 20 mL and 10 mL. Blockade was considered effective when analgesia was present in all sensory nerves distal to the elbow . RESULTS Onset ( 8.8 + /- 2.3 min versus 10.2 + /- 2.4 min ; p-value = 0.010 ) was significantly shorter in the transarterial group . Complete sensory block of all four nerves ( median , ulnar , radial and musculocutaneus ) was achieved in 92.5 % versus 83.3 % for multiple nerve stimulation group and transarterial group , respectively , without significant difference ( p = 0.68 ) . Musculocutaneous nerve was significantly easier to be blocked with the aid of peripheral nerve stimulator ( p = 0.034 ) . CONCLUSIONS Both MNS technique for axillary block with nerve stimulator ( 3 injections ) and transarterial technique ( 2 injections ) promote similar results . Musculocutaneous nerve is more easily blocked with the aid of peripheral nerve stimulator . MNS technique has required less supplementary blocks and has delayed beginning of surgery Background and Objectives : A triple-injection technique ( injections at the median , musculocutaneous , and radial nerves ) for axillary block affords a high incidence of complete block ( all the nerves below the elbow ) . However , in certain surgeries , only 1 or 2 nerves are involved in the surgical field . The aim of this prospect i ve r and omized study was to test the effectiveness of surgical anesthesia of a " selective " approach in which only the nerves involved in surgery were electrically located and injected . Methods : Three types of surgery were selected . Type 1 included surgery on the fifth finger , type 2 included superficial surgery ( without bone involvement ) on the palm or on the dorsum of the h and , and type 3 included any surgery on the first 3 fingers . For each type , 138 patients were enrolled and divided into 2 groups : group SEL in which only the nerves involved in the surgical field ( 1 or 2 ) were located and injected and group TNS in which a st and ard triple-nerve stimulation technique was used . Results : A lower rate of surgical anesthesia ( 84 % vs 92 % ; P < 0.05 ) was recorded in group SEL considered as a whole : this was mainly due to the significant difference recorded in type 2 surgery ( 75 % vs 93 % ; P < 0.05 ) . More patients needed intravenous administration of fentanyl for tourniquet pain ( 18 % vs 8 % ; P < 0.005 ) and of midazolam for intraoperative anxiety ( 20 % vs 8 % ; P < 0.005 ) in group SEL considered as a whole . In type 1 , improved patient comfort at block performance ( P < 0.05 ) , a 7-min saving on total anesthetic time ( P < 0.001 ) , and a higher need for midazolam administration ( P < 0.05 ) were recorded in group SEL . In type 2 , a higher need for midazolam administration ( P < 0.05 ) was recorded in group SEL . In type 3 , no clinical ly significant differences between the groups were recorded . Conclusions : A st and ard triple-nerve stimulation technique seems to be preferable to the selective approach even when a limited number of nerves are involved in the surgical field The perivascular technique of axillary brachial plexus block results in incomplete block of radial and musculocutaneous nerves in 10 - 20 % of patients . With the transarterial technique and a large dose of mepivacaine , success rates of 99 % have been reported . We have compared the clinical efficacy of these techniques in 50 patients using 1 % mepivacaine 45 ml with adrenaline . If required , the block was supplemented with additional blocks of single nerves or i.v . alfentanil . Additionally , eight patients in each group were studied with computed tomography after contrast medium was added to 0.5 % bupivacaine 40 ml . There were no statistically significant differences in sensory or motor block between the groups at 20 min or in the plasma concentrations of mepivacaine measured 0 - 45 min after injection . In the CT scans , both proximal and distal spread of the contrast medium were more common after perivascular than after transarterial block . The distribution of the contrast medium was not related to the efficacy of the block Perivascular axillary blockade was performed on 90 patients with the aid of a catheter technique . The patients were r and omly allocated to receive either 40 , 50 or 60 ml of 1 % mepivacaine with adrenaline 1:200,000 . Blood concentrations of mepivacaine were measured up to 90 min after injection in seven , eight and ten of the patients from the three groups . Sensory and motor blockade was evaluated 20 , 30 and 40 min after injection . All groups showed the same temporal development of the blockade , i.e. improval of the blockade during the period from 20 to 40 min after injection , but no difference was found in the sensory or motor blockade between the three groups . However , a further analysis of the incomplete blockades showed a better quality of the sensory blockade in the groups given 50 and 60 ml than in the group given 40 ml . None of the 90 patients showed any signs of systemic toxic reactions . The mean peak values of blood concentrations were 0.5‐1.0 μg/ml higher in the groups A given 50 ml and 60 ml than in the group given 40 ml . On the basis of the present and two previous investigations on the dose response in perivascular axillary blockade , a dose of 50 ml 1 % mepivacaine with adrenaline or I r another equivalent drug with vasoconstrictor is recommended Endoscopic carpal tunnel release has the advantage over open release of reduced tissue trauma and postoperative morbidity . Limited open carpal tunnel release has also been shown to have comparable results , but is easier to perform and is safer . We have compared the results of both techniques in a prospect i ve , r and omised trial . Thirty patients with bilateral carpal tunnel syndrome had simultaneous bilateral release . The technique of release was r and omly allocated to either two-portal endoscopic release ( ECTR ) or limited open release using the Strickl and instrumentation ( LOCTR ) . The results showed that the outcome was similar at follow-up of one year using both techniques . However , the LOCTR group had significantly less tenderness of the scar at the second and fourth postoperative week ( p < 0.01 ) . There was also less thenar and hypothenar ( pillar ) pain after LOCTR . Subjective evaluation showed a preference for LOCTR OBJECTIVE To investigate the clinical effects and safety of the technique of axillary approach brachial plexus blocking by ultrasound-guided four points via one-puncture . METHODS Eighty patients scheduled for elective operation were r and omly divided into 2 equal groups to undergo axillary approach brachial plexus blocking by ultrasound-guided four points via one-puncture technique ( Group U ) or nerve stimulator-guided brachial plexus blocking ( Group N ) . The main branches of brachial plexus ( radial , median , ulnar , and musculocutaneous nerves ) were localized by ultrasound-guided or nerve stimulator-guided techniques . In Group U 8 ml of mixed anesthetic solution containing isovolumetric 0.75 % ropivacaine and 2 % lidocaine was injected into the 4 main branches of brachial plexus , with a total volume of 32 ml . The ultrasonic manifestations of the brachial plexus and its surrounding tissues were observed . The values of diameter and depth of the 4 nerves and the distance of the musculocutaneous nerve to the midpoint of axillary artery were measured . The manipulation time , onset time , maintaining time , efficacy of blocking , and incidence of complication were recorded . RESULTS The manipulation time of Group U was 5.2 + /- 2.1 min , significantly shorter than that of Group N ( 14.6 + /- 3.2 min , P = 0.000 ) , The onset times of the median , radial , and ulnar nerves of Group U were 3.3 + /- 1.9 min , 3.0 + /- 1.7 min , and 3.4 + /- 1.9 min respectively , all significantly shorter than those of Group N ( 4.6 + /- 2.0 min , 7.3 + /- 7.4 min , and 6.4 + /- 6.1 min respectively , P < 0.01 or P < 0.05 ) . The anesthetic success rate of Group U was 100 % , significantly higher than that of Group N ( 77.5 % , P = 0.005 ) . The rate of accidental puncture to blood vessel of Group U was 0 , significantly lower than that of Group N ( 40 % , P = 0.000 ) . CONCLUSION With significantly higher anesthetic success rate , shorter manipulation time and onset time , and lower complication rate , the technique of axillary approach brachial plexus blocking by ultrasound-guided four points via one-puncture is a safe and reliable blocking method in comparison with the nerve stimulator-guided method Perivascular axillary blockade was performed on 90 patients with the aid of a catheter technique . All blockades were performed by the same anaesthetist , who practised perivascular axillary blockade three or four times a day . The patients were r and omly allocated to three groups . The injected volume of local anaesthetic was constant in each group : 40 ml mepivacaine with adrenaline . The concentration and , consequently , the amount ( mg ) were variable factors : ½% ( 200 mg ) , 1 % ( 400 mg ) and 1½% ( 600 mg ) . Sensory and motor blockade were tested 30 min after each injection . All three groups showed a high incidence of analgesia ( 70%‐100 % ) in all cutaneous segments , and none of the blockades showed total failure of the sensory blockade . The lowest incidence of sensory blockade was found in the areas innervated by the axillary , the radial and the musculocutaneous nerves , but no difference was found between the groups . However , the motor blockade was found to improve with increasing concentration of local anaesthetic solution BACKGROUND Axillary plexus blocks are usually guided by ultrasound , but alternative methods may be used when ultrasound equipment is lacking . For a nonultrasound-guided axillary block , the need for three injections has been question ed . OBJECTIVES Could differences in block success between single , double and triple deposits methods be explained by differences in local anaesthetic distribution as observed by MRI ? DESIGN A blinded and r and omised controlled study . SETTING Conducted at Oslo University Hospital , Rikshospitalet , Norway from 2009 to 2011 . PATIENTS Forty-five ASA 1 to 2 patients scheduled for surgery were r and omised to three equally sized groups . All patients completed the study . INTERVENTIONS Patients in the single-deposit group had an injection through a catheter parallel to the median nerve . In the double-deposit group the patients received a transarterial block . In the triple-deposit group the injections of the two other groups were combined . Upon completion of local anaesthetic injection the patients were scanned by MRI , before clinical block assessment . The distribution of local anaesthetic was scored by its closeness to terminal nerves and cords of the brachial plexus , as seen by MRI . The clinical effect was scored by the degree of sensory block in terminal nerve innervation areas . MAIN OUTCOME MEASURES Sensory block effect and MRI distribution pattern . RESULTS The triple-deposit method had a higher success rate ( 100 % ) than the single-deposit method ( 67 % ) and the double-deposit method ( 67 % ) in blocking all cutaneous nerves distal to the elbow ( P = 0.04 ) . The patients in the triple-deposit group most often had the best MRI scores . For any nerve or cord , at least one of the single-deposit or double-deposit groups had a similarly high MRI score as the triple-deposit group . CONCLUSION Distal to the elbow , the triple-deposit method had the highest sensory block success rate . This could be explained to some extent by analysis of the magnetic resonance images . TRIAL REGISTRATION Clinical Trials.gov identifier : NCT01033006 This prospect i ve , r and omized , double-blind study was undertaken to evaluate the success rates of axillary brachial plexus block performed with the help of a peripheral nerve stimulator when either one , two or four of the major nerves of the brachial plexus were located . Seventy-five patients undergoing upper limb surgery were r and omly allocated to one of the following five groups according to the nerve and number of nerves to be located ; G-1 : musculo-cutaneous , radial , median and ulnar nerves ; G-2 : musculo-cutaneous plus one of the other three nerves ; G-3 : radial nerve ; G-4 : median nerve ; G-5 : ulnar nerve . The sensory block was evaluated before surgery and cutaneous anaesthesia was considered to be present when the needles of a Wartenberg Pinwheel were no longer felt in all the dermatomes of the nerves implicated in the surgical site . Otherwise , the block was considered to need completion before surgery . Only one out of the 15 patients in G-1 and G-2 needed completion of their block before surgery whereas seven out of 15 for G-3 and eight out of 15 for G-4 and G-5 needed completion of their block ( P < 0.01 ) . We conclude that when performing an axillary block with the help of a peripheral nerve stimulator , stimulation of the musculo-cutaneous nerve and one other nerve or stimulation of all four major nerves of the brachial plexus gives a higher success rate than stimulation of only one nerve , whether the stimulated nerve is the median , radial or ulnar . RésuméLa présente étude en est une prospect i ve , avec distribution au hasard , et à double insu . Elle avait pour but d’évaluer l’influence du nombre et de la nature des nerfs stimulés lorsque le bloc du plexus brachial est réalisé par approche axillaire à l’aide d’une technique de neurostimulation . Soixante et quinze patients soumis à une chirurgie du membre supérieur ont été distribués de façon aléatoire dans l’un des cinq groupes suivants selon le nerf et le nombre de nerfs localisés par neurostimulation ; G-1 : nerfs musculo-cutané , radial , médian et cubital ; G-2 : nerfs musculo-cutané , et l’un des trois autres nerfs majeurs du plexus brachial ( médian , radial ou cubital ) ; G-3 : nerf radial ; G-4 : nerf median ; G-5 : nerf cubital . Le bloc sensitif a été évalué avant la chirurgie et une anesthésie cutanée était considérée présente qu and les aiguilles d’une roulette de Wartenburg n ’ étaient plus perçues dans tous les territoires cutanés des nerfs impliqués dans le site chirurgical . Sinon , le bloc a été considéré comme devant être complété . Un seul patient sur 15 dans les G-1 et 2 a necessite un complément de son bloc avant la chirurgie , alors que sept patients sur 15 dans le G-3 et huit sur 15 dans les G-4 et 5 ont necessite un tel complement avant la chirurgie ( P < 0.01 ) . Nous concluons que lorsque nous réalisons un bloc axillaire avec l’aide d’un stimulateur nerveux périphérique , la stimulation du nerf musculo-cutané et de l’un des trois autres nerfs majeurs du plexus brachial , ou la stimulation des quatre principaux nerfs du plexus brachial conduisent à un taux de réussite plus élevé que la stimulation d’un seul nerf que ce soit le médian , le radial ou le cubital Comparison of the trans-arterial and Winnie techniques of axillary brachial plexus block was made in two groups of patients . This study did not find any statistical difference between the two techniques This prospect i ve , r and omized , double-blind study compared two techniques of axillary brachial plexus block using a peripheral nerve stimulator . Both groups received initial musculocutaneous nerve block followed by either a single injection on median nerve stimulation ( group 1 ) or a double injection divided between median and radial nerves ( group 2 ) . All 60 patients received a total of 30 ml of lidocaine 15 mg/ml with epinephrine 5 microg/ml . Complete sensory blockade of all six peripheral nerves occurred in 53 % and 97 % of patients in groups 1 and 2 , respectively ( P<0.001 ) , with a more rapid onset of blockade occurring in group 2 patients ( P<0.001 ) . Complete motor blockade was evident in 30 % and 83 % of patients in groups 1 and 2 , respectively ( P<0.001 ) Background and Objectives The multiple-injection technique for axillary block , in which the main 4 nerves of the plexus are located by a nerve stimulator and separately injected , has been shown to produce a high success rate . However , this technique may prove to be more difficult and time-consuming than other methods . Therefore , a simplified technique , with a reduced number of injections , might be desirable . A comparison between 2- and 3-injection techniques was made in the present double-blind study . Methods One hundred patients were r and omly allocated to 2 groups . In group 3N , the radial , median , and musculocutaneous nerves were located by a nerve stimulator and injections made . In group 2N , the radial and median nerves were located and injections made . Forty milliliters of local anesthetic was used . Results A greater success rate for anesthetizing the musculocutaneous nerve was found in group 3N ( 98 % v 80 % ; P < .005 ) . No differences between the groups were found in the success rate for blocking the radial , median , and ulnar nerves . The rate of complete block ( all the sensory areas distal to the elbow ) was 90 % in group 3N and 76 % in group 2N . The time to perform the block was shorter in group 2N ( 5 ± 1 v 6 ± 1 minutes ; P < .001 ) . Conclusions The 2-injection technique offers a success rate in blocking the 3 nerves innervating the h and similar to that obtained with the 3-injection technique . The latter approach should be considered when the musculocutaneous nerve distribution is involved in the surgical area STUDY OBJECTIVE To investigate the comfort and satisfaction of patients with trauma of the upper limb during two different techniques of axillary brachial plexus block , electrical nerve stimulation and fascial pop . DESIGN R and omized- prospect i ve , observational study . SETTING University surgical center . PATIENTS 100 ASA physical status I and II patients undergoing surgery for trauma of the h and and forearm . INTERVENTIONS Patients received axillary brachial plexus block with a mixture of 0.5 % bupivacaine and 2 % lidocaine . They were then allocated to one of two groups to receive either electrical nerve stimulation ( Group 1 , n = 50 ) , or fascial pop technique ( Group 2 , n = 50 ) for nerve location . MEASUREMENTS Data were collected on patient demographics , surgery , frequency of complications , and sedation required during the block . Discomfort during the block and surgical comfort were quantified by visual analog scale ( 0 - 10 ) . Satisfaction was determined by the following scale : very satisfied , satisfied , dissatisfied , and very dissatisfied . Patients also indicated if in the future they would like to receive the same method of anesthesia . MAIN RESULTS No differences in demographic or surgical data were found . No serious complications were observed . Eighteen Group 1 patients ( 36 % ) and none in Group 2 needed sedation during the blocks . Discomfort during the procedures was greater in Group 1 than Group 2 ( 4.5 + /- 1.2 vs 1.5 + /- 1 , P < 0.05 ) , while patients reported good surgical comfort with both techniques ( 2.4 + /- 2.9 vs 2.2 + /- 2.1 , NS ) . Eighteen patients in Group 1 and 48 patients in Group 2 would accept the same block for future surgery . CONCLUSIONS In trauma patients , the fascial pop technique is effective , reduces sedation during axillary brachial plexus block , and has a higher patient acceptance rate than the electrical nerve stimulation technique BACKGROUND AND OBJECTIVES The multiple-injection technique for axillary block , in which the 4 distal nerves of the plexus are located by a nerve stimulator and separately injected , has been shown to produce a rapid onset and a high success rate . However , this technique may be more difficult and time consuming than other axillary block methods . A simplified multiple-nerve stimulation technique , in which the ulnar nerve was not located , was compared in the present double-blind study to the 4-injection approach . METHODS Eighty-four patients were r and omly allocated to 2 groups . In group IV , all 4 distal nerves of the plexus were located by a nerve stimulator and injections made . In group III , all the nerves but the ulnar were located and injections made . The block was defined as complete when analgesia was present in all the sensory areas distal to the elbow . RESULTS The time to perform the block was shorter in group III ( 5 + /- 2 v 8 + /- 3 minutes ; P < .001 ) . Block performance pain was lower in group III patients ( 8 + /- 2 v 13 + /- 2 mm ; P < .001 ) . The onset time ( 15 + /- 6 v 16 + /- 7 minutes ) and the frequency ( 90 % v 92 % ) of complete block were not different between the groups . CONCLUSIONS A triple-injection method of axillary block in which the ulnar nerve was not purpose ly located provides a spread and a latency of sensory block equal to that obtained with a 4-injection technique . A shorter performance time is an advantage of this approach INTRODUCTION : In this prospect i ve , r and omized , double-blind study , we compared the effectiveness and time efficiency of perioperative axillary blocks performed via 2 different techniques , 1 involving 2 and the other 4 separate skin punctures . METHODS : One hundred twenty patients undergoing upper limb surgery were r and omized to receive either ( 1 ) an axillary brachial plexus block involving 2 injections , with 30 mL local anesthetic injected posterior to the axillary artery ( with redirection , as needed , to achieve circumferential spread ) , plus 10 mL local anesthetic to the musculocutaneous nerve , guided by ultrasound ( group 1 , n = 56 ) ; or ( 2 ) 4 separate 10-mL injections to the median , ulnar , radial , and musculocutaneous nerves , using a combined ultrasound and neurostimulation technique ( group 2 , n = 58 ) . All patients received 40 mL of 0.5 % ropivacaine with 1:400,000 epinephrine . The primary outcome was the success rate of the block , defined as anesthesia adequate for surgery . Secondary outcomes were the time to administer the block , time to the onset of motor-sensory block , time to surgical readiness , and incidence of adverse events . RESULTS : The 2-injection technique was slightly faster to administer ( 8 vs 11 minutes , P = 0.003 ) . The mean nerve block score was slightly higher for the 4-injection group at the 10- , 15- , 20- , and 30-minute time points , but the cumulative percentages of blocks having taken effect were not significantly different over these time points , at 0.0 % , 5.4 % , 12.5 % , and 37.5 % among those who had received a 2-injection block versus 6.9 % , 10.4 % , 19.0 % , and 48.3 % , respectively , with the 4-injection block ( P = 0.20 ) . There was no difference in the percentage of patients with complete block by 30 minutes ( 32.1 % vs 37.5 % , P = 0.55 ) or in final block success rates ( 89.3 % vs 87.9 % , P = 0.99 ) . CONCLUSIONS : An ultrasound-guided 2-injection axillary block may be as effective as , and more time efficient than , a 4-injection technique Perivascular axillary blockade was performed on 60 patients with the aid of a catheter technique . The patients were r and omly allocated to two groups . All patients received the same dose of local anaesthetic : 60 ml of mepivacaine 1 % with adrenaline , but one group received the dose as a bolus injection , whereas the other group received the dose as fractional injections of 30 + 30 ml with an interval of 20 min . Blood concentrations of mepivacaine were measured up to 90 min after injection of local anaesthetic . Sensory and motor blockade were evaluated 20 , 30 and 40 min after injection . Forty minutes after the last injection of local anaesthetic , there was no difference between the blockades of the two groups , except for the sensory blockade of the lower lateral cutaneous nerve of the arm , in which the frequency of analgesia was 90 % after bolus injection and 63 % after fractional injections . There was no difference in blood concentrations of mepivacaine between the two groups . None of the 60 patients showed any sign of systemic toxic reactions . Fractional injection of local anaesthetic in perivascular axillary blockade does not offer any advantage over bolus injection with regard to the result ing blockade We undertook this prospect i ve , r and omized study to compare the success rate , time spent performing the blocks , onset time of surgical anesthesia , presence of complete motor blockade , and lidocaine plasma concentrations between conventional axillary block and a new approach at the midhumeral level . Both techniques were performed using a peripheral nerve stimulator . Two nerves were located at the axillary crease , whereas four nerves were located at the midhumeral level . Sixty patients undergoing upper limb surgery were assigned to one of the two techniques . The sensory block was evaluated before surgery for all of the distributions of the four major nerves of the upper extremity . A subset of patients had lidocaine plasma concentrations determined . Times to perform the blocks , mean maximum plasma lidocaine concentration , and time to peak concentration were not different between groups . The success rate of the block , as well as the incidence of complete motor blockade , was greater with the midhumeral approach compared with the axillary approach . However , the onset time to complete anesthesia of the upper extremity was shorter in the axillary approach . For brachial plexus anesthesia , we conclude that the midhumeral approach provided a greater success rate than the traditional axillary approach . ( Anesth Analg 1997;84:1058 - 62 Surgical procedures to the distal humerus , elbow , and proximal forearm are ideally suited to regional anesthetic techniques . Selection of the preferred approach is determined by the innervation of the surgical site , the risks of regional anesthesia-related complications , and the preference and experience of the anesthesiologist . The axillary approach to the brachial plexus is the most commonly used because of its ease of performance , patient acceptance , safety , and reliability , particularly for h and and forearm surgery . Nerve location technique does not affect success rate with the supraclavicular and interscalene approaches but it does with axillary approaches . The purpose of this study was to evaluate three techniques of plexus identification in axillary blockade . Sixty-nine American Society of Anesthesiologists grade I to II patients who had undergone orthopedic or traumatological surgical procedures on the upper extremity during a period of 1 year were chosen . After premedication , patients were divided r and omly into three groups according to the technique of plexus identification . Group A ( n = 23 ) consisted of those treated with the Winnie technique ; group B ( n = 23 ) consisted of those treated with the transarterial technique ; group C ( n = 23 ) consisted of those treated with the combination technique . Axillary blockade performed using the combined technique had higher a success rate than blockade performed with the transarterial and Winnie techniques . Our results suggest that all three techniques are reliable for axillary blockade . But the onset , complete blockade time , and quality of analgesia were better with the combined technique than with the transarterial and Winnie techniques Perivascular axillary blockade was performed on 233 patients with the aid of a catheter technique . All patients received a primary injection of 50 ml of mepivacaine 1 % with adrenaline . Sensory blockade was evaluated 20 , 30 and 40 min after injection , and a complete sensory blockade was found in 90 ( 39 % ) , 131 ( 57 % ) and 146 ( 63 % ) , respectively . The blockade effect of a supplementary perivascular injection of 20 ml of the same agent was investigated on the remaining 87 blockades , which could be divided into three categories : 1 ) blockades which at 20 min showed lack of analgesia in several cutaneous segments of the h and ( 34 patients ) ; 2 ) blockades which at 30 min showed a total lack of sensory blockade within a limited area ( 29 patients ) ; and 3 ) blockades which at 40 min showed signs of blockade of all cutaneous segments , but one or several segments were not blocked with an intensity compatible with surgery ( 24 patients ) . Blockades of categories 1 and 2 were at 20 and 30 min , respectively , r and omly allocated to control or to perivascular supplementation groups , while blockades of category 3 all had supplementation at 40 min . Sensory blockade was reevaluated 10 and 20 min after group allocation , and it was found that perivascular supplementation had no significant effect on the sensory blockade in category 1 and 2 , while 68 % of the blockades in category 3 improved to a complete blockade . It was concluded that the effect of a supplementary perivascular dose of local anaesthetic could be judged as acceptable with regard to intensifying an insufficient sensory blockade , but that it was incapable of extending the blockade into areas which were totally unblocked after the primary injection . On the basis of a previous and the present investigation , we have suggested practical , simple guidelines which might help the anaesthetist in deciding on his course of action when faced with an inadequate axillary blockade Background : Brachial plexus block by the coracoid approach does not require arm abduction and may be more effective than the axillary approach because of a more proximal injection of local anaesthetic . However , the clinical usefulness of the coracoid approach has not been tested in prospect i ve controlled trials . The present r and omized , observer‐blinded study compared success rates , time to obtain a complete block , frequency of adverse effects and block discomfort in two groups of 30 patients , anaesthetized for h and surgery using either the coracoid or the axillary approach to the brachial plexus Background This prospect i ve , r and omized , observer-blinded study compared double- , triple- , and quadruple-injection ultrasound (US)–guided axillary brachial plexus block ( AXB ) for upper-extremity surgery . Methods One hundred twenty patients were r and omly allocated to receive a double- ( n = 40 ) , triple- ( n = 40 ) , or quadruple-injection ( n = 40 ) US-guided AXB . The local anesthetic agent ( lidocaine 1.5 % with epinephrine 5 & mgr;g/mL ) and total volume ( 35 mL ) were identical in all subjects . For all 3 groups , the musculocutaneous nerve was identified and anesthetized first . Subsequently , a perivascular technique was performed . Lidocaine was deposited at the 6-o’clock position of the axillary artery for the 2-injection group . For the 3- and 4-injection groups , injections were carried out at the 12-/6-o’clock and 2-/10-/6-o’clock positions , respectively . During the performance of the block , the performance time , number of needle passes , and complications ( vascular puncture , paresthesia ) were recorded . Subsequently , a blinded observer assessed the onset time , block-related pain scores , and success rate ( surgical anesthesia ) . The main outcome variable was the total anesthesia-related time ( sum of performance and onset times ) . Results No differences were observed among the 3 groups in terms of total anesthesia-related time ( 29.2–31.4 mins ) , success rate ( 90.0%–97.5 % ) , block-related pain scores , vascular puncture , and paresthesia . Compared with its 3- and 4-injection counterparts , the double-injection technique required fewer needle passes ( 4.0 ± 1.6 vs 5.2–6.0 ± 1.7–2.8 ; both P ⩽ 0.001 ) . Conclusions Double- , triple- , and quadruple-injection US-guided perivascular AXB result in comparable success rates and total anesthesia-related times . Because it requires fewer needle passes , the double-injection technique provides a simple alternative for US-guided AXB Background : High‐dose transarterial ( TA ) technique results in high effectiveness of the axillary block . The technique is fast and simple , but does not produce a satisfactory success rate when using the manufacturer ’s recommended dose of mepivacaine . The multiple nerve stimulation ( MNS ) technique requires more time and experience . This double‐blind study compared effectiveness , safety and the time used to obtain an effective analgesia in 101 patients , having an axillary block by either TA or MNS techniques BACKGROUND The aim of this study was to compare the efficacy of axillary brachial plexus block using an ultrasound-guided method with the nerve stimulator-guided method . We also compared the efficacy of ultrasound-guided single-injection with those of double-injection for the quality of the block . METHODS Ninety patients scheduled for surgery of the forearm or h and were r and omly allocated into three groups ( n = 30 per group ) , i.e. , nerve stimulator-guided and double-injection ( ND ) group , ultrasound-guided and double-injection ( UD ) group , and ultrasound-guided and single-injection ( US ) group . Each patient received 0.5 ml kg(-1 ) of 1.5 % lidocaine with 5 mg kg(-1 ) epinephrine . Patients in the ND group received half the volume of lidocaine injected near the median and radial nerves after identification using a nerve stimulator . Patients in the UD group received half the volume of lidocaine injected around the lateral and medial aspects of the axillary artery , while those in the US group were given the entire volume near the lateral aspect of the axillary artery . The extent of the sensory blockade of the seven nerves and motor blockades of the four nerves were assessed 40 min after the performance of axillary brachial plexus block . RESULTS Seventy percent of the patients in the ND and US groups as well as 73 % of the patients in the UD group obtained satisfactory sensory and motor blockades . The success rate of performing the block was 90 % in patients in the ND and UD groups and 70 % in the US group . The incidence of adverse events was significantly higher in the ND group ( 20 % ) compared with that in the US group and the UD group ( 0 % ; p = 0.03 ) . CONCLUSIONS Ultrasound-guided axillary brachial plexus block , using either single- or double-injection technique , provided excellent sensory and motor blockades with fewer adverse events Background This prospect i ve , r and omized , observer-blinded study compared perivascular ( PV ) and perineural ( PN ) ultrasound-guided axillary brachial plexus block ( AXB ) for upper extremity surgery . Methods Fifty patients were r and omly allocated to receive a PV ( n = 25 ) or PN ( n = 25 ) ultrasound-guided AXB . The local anesthetic agent ( lidocaine 1.5 % with epinephrine 5 & mgr;g/mL ) and total volume ( 32 mL ) were identical in all subjects . For both groups , the musculocutaneous nerve was first located and then anesthetized using 8 mL. Subsequently , in the PV group , 24 mL was deposited dorsal to the axillary artery ( 6-o’clock position ) . In contrast , for the PN group , the median , ulnar , and radial nerves were individually anesthetized with volumes of 8 mL. During the performance of the block , the performance time , number of needle passes , and complications ( vascular puncture , paresthesia ) were recorded . Subsequently , a blinded observer assessed the onset time , block-related pain scores , and success rate ( surgical anesthesia ) . The main outcome variable was the total anesthesia-related time ( sum of performance and onset times ) . Results No differences were observed between the 2 groups in terms of success rate ( 92%–96 % ) , total anesthesia-related time ( 27.1–29.0 min ) , and block-related pain scores . However , the PV technique required fewer needle passes ( 3.5 [ SD , 1.0 ] vs 8.2 [ SD , 2.2 ] ; P = 0.000 ) as well as a shorter performance time ( 8.2 [ SD , 2.3 ] vs 15.7 [ SD , 3.2 ] min ; P = 0.000 ) and was associated with a lower incidence of paresthesia ( 8 vs 52 % ; P = 0.001 ) . In contrast , the PN technique result ed in a quicker onset time ( 13.8 [ SD , 7.0 ] vs 18.9 [ SD , 7.0 ] min ; P = 0.021 ) and a decreased incidence of vascular puncture ( 0 vs 24 % ; P = 0.01 ) . Conclusions Perivascular and PN ultrasound-guided AXBs result in comparable success rates and total anesthesia-related times . Because of fewer needle passes and a shorter performance time , the PV technique provides a simple alternative for ultrasound-guided AXB Background : The single‐injection axillary block is rapidly performed but gives unpredictable results . Axillary block by multiple nerve stimulation technique ( MNS ) gives better results , but takes longer to perform . Transarterial ( TA ) injections of high doses of local anaesthetics are very successful . This double‐blind study compared both block effectiveness and anaesthesiologic time consumption in 100 patients , having an axillary block by either TA or MNS techniques Purpose To compare anesthetic time , success rate and adverse effects of axillary block by single or multiple injections of local anesthetic . Methods Two groups of patients were studied . In group T ( targeted injections , n = 53 ) the four terminal nerves were located by electrical stimulation , and anesthetized with 5 ml mepivacaine 1 % with epinephrine 5 μg·ml−1 ( MEPE ) . In group S ( single injection , n = 53 ) 80 mL MEPE 1 % were injected into the neurovascular sheath , transarterially or after eliciting paresthesia . Patchy blocks were supplemented after 30 min . The patient was ready for surgery when analgesia was present in all areas distal to the elbow . Results The block was complete at 11 min ( 6–15 ) in Group T and 7 min ( 5–13 ) in group S , P < 0.01 . Supplementation was required in 46 % in group S compared with 13 % in group TP < 0.001 : anesthesia time was 32 min ( 19–52 ) in group T and 39 min ( 16–58 ) in group S , P=0.02 . The average doses of MEPE were 3.5 mg·kg−1 ( 2.4–5.6 ) in T group and 12.0 mg·kg−1 ( 8.9–16.4 ) , in S group . However , 22 % of patients in group T and 4 % in group S reported tourniquet pain , P=0.02 . Paresthesia was elicited in 42 % of patients in group S and 8 % in group TP < 0.001 . Conclusions Small targeted injections of MEPE reduce total anesthetic time , give better spread of analgesia in the h and and forearm , and may be safer than a single large injection . RésuméObjectifComparer la durée de l’anesthésie , le taux de succès et les effets indésirables à la suite d’un blocage axillaire au moyen d’injections uniques ou multiples d’anesthésique local . MéthodeLes patients ont été répartis en deux groupes : dans le groupe C ( injections ciblées , n = 53 ) , les quatre nerfs terminaux ont été localisés par stimulation électrique et insensibilisés avec 5 ml de mépivacaïne 1 % et 5 μg·ml−1 d’épinéphrine ( MEPE ) ; dans le groupe U ( injection unique , n = 53 ) , 80 ml de MEPE 1 % ont été injectés dans la gaine neurovasculaire , de façon transartérielle ou après avoir provoqué la paresthésie . Les blocages parcellaires ont été complétés après 30 min . Le patient était prêt pour l’opération qu and l’analgésie était présente dans toutes les aires distales au coude . RésultatsLe blocage a été complet après 11 min ( 6–15 ) dans le groupe C et 7 min ( 5–13 ) dans le groupe U , P < 0,01 . Ladministration d’un supplément a été nécessaire chez 46 % des patients du groupe U et 13 % du groupe C , P < 0,001 : la durée de l’anesthésie a été de 32 min ( 19–52 ) dans le groupe C , et de 39 min ( 16–58 ) dans le groupe U , P = 0,02 . Les doses moyennes de MEPE ont été de 3,5 μg·ml−1 ( 2,4–5,6 ) dans le groupe C et de 12,0 μg·ml−1 ( 8,9–16,4 ) , dans le groupe U. Toutefois , 22 % des patients du groupe C et 4 % du groupe U se sont plaints de douleur liées au garrot , P = 0,02 . La paresthésie a été provoquée chez 42 % des patients du groupe U et 8 % du groupe C , P < 0,001 . Conclusion Des doses faibles et ciblées de MEPE réduisent la durée totale de l’anesthésie , fournissent une plus gr and e étendue de l’analgésie dans la main et l’avant-bras et peuvent être plus sûres que l’injection unique d’une forte dose Background Axillary brachial plexus block under neurostimulation is commonly used for upper limb surgery , but it is sometimes recognized as an uncomfortable technique , with most patients identifying electrical stimulation as an unpleasant moment . Ultrasound-guided regional anaesthesia , which becomes an increasingly popular technique , does not require electrical stimulation and then should theoretically improve axillary block placement comfort . The aim of this study was to compare the comfort of the patients during axillary block placement with neurostimulation and ultrasound guidance using either the out-of-plane or the in-plane approach . Methods Consecutive patients were prospect ively enrolled in three equal groups : neurostimulation , ultrasound out-of-plane and ultrasound in-plane approaches . A score was used to measure the comfort of the patients during axillary blocks placement . This score included three criteria : maximum pain intensity perceived during block placement measured using a visual analogue scale ( 0 , no pain and 100 , maximal or worse imaginable pain ) , the number of unpleasant events declared by the patients and the satisfaction of the patient ( unsatisfied , acceptable , satisfied , very satisfied ) . The comfort score was calculated as the sum of each criterion , which was attributed a value of 0 or 1 : visual analogue scale ( ≤30/100 , 1 ; > 30/100 , 0 ) , number of unpleasant events ( 0 , 1 ; ≥1 , 0 ) and satisfaction ( satisfied or very satisfied , 1 ; acceptable or unsatisfied , 0 ) . Procedures of axillary blocks placement result ing in a comfort score of 3 and 2 were arbitrary considered as very comfortable and comfortable , respectively . Success rate of axillary blocks , time to perform block and complications related to procedures were noted . Results One hundred and twenty patients were included . In the ultrasound out-of-plane group , 55 % ( 22/40 ) and 25 % ( 10/40 ) of the procedures were very comfortable and comfortable as compared with 32 % ( 13/40 , P < 0.05 ) and 20 % ( 8/40 , P < 0.01 ) in the ultrasound in-plane group and 25 % ( 10/40 , P < 0.01 ) and 8 % ( 3/40 , P < 0.01 ) in the neurostimulation group , respectively . Duration of axillary placement was significantly smaller in the ultrasound out-of-plane group as compared with that of in-plane approaches ( P < 0.05 ) and neurostimulation ( P < 0.01 ) . Conclusion The present study showed that the ultrasound approaches were less painful and more comfortable than neurostimulation to place axillary blocks . We also showed that , although pain intensity result ing from blocks placement was similar with the ultrasound approaches , very comfortable procedures were more frequent with the out-of-plane than with the in-plane approach Background and Objectives . The present study was performed at the Crystal Clinic Surgery Center , an outpatient free-st and ing surgicenter specializing in orthopedic surgery , to determine the incidence of both neurologic and vascular sequelae associated with exclusive use of a transarterial approach to axillary brachial plexus block in order to assess the technique 's safety and efficacy . Methods . The prospect i ve consecutive study involved 1,000 adult patients scheduled for surgery using axillary brachial plexus block . The transarterial approach was performed on all patients using a medium-bevel 24-gauge Jelco 1 - 5-inch needle . Data tabulated included the incidence of neurovascular complications and the outcome of successful axillary brachial plexus anesthesia . Results . Two patients presented with a sensory paresthesia ( 0.2 % ) in the distribution of the ulnar nerve and the musculocutaneous nerve that most likely occurred during supplementation of an incomplete block . Three patients presented with upper-arm myalgias ( 0.3 % ) related to tourniquet injury . After the operation , two patients developed reflex sympathetic dystrophy , which responded to stellate ganglion blocks . Vascular complications , including transient arterial spasm in 10 of 996 ( 1 % ) , unintentional intravascular injection in 2 of 996 ( 0.2 % ) , and small ( 0 - 2 cm ) hematoma formation in 2 of 996 ( 0.2 % ) , were recognized but did not require any intervention other than close observation . The study revealed a complete block in 88.8 % of cases , an incomplete block requiring supplemental local anesthesia in 10 % of cases , and a complete block failure in 1.2 % . Conclusions . This study demonstrated the safety and efficacy of the transarterial technique in achieving brachial plexus block We have assessed prospect ively the time to readiness for surgery following axillary block ( sum of block performance and latency times ) in 80 patients . The brachial plexus was identified using a nerve stimulator , and anaesthetized with 45 mL of mepivacaine 1 % with adrenaline 5 micrograms mL-1 . In group 1 ( single injection ) the whole volume of mepivacaine was injected after locating only one of the plexus nerves . In group 2 ( multiple injections ) at least three plexus nerves were located , and the volume of mepivacaine was divided between them . Sensory block was assessed by a blinded observer every 10 min . Patchy analgesia was supplemented after electrolocating the unblocked nerves after 20 , 30 or 40 min . The patient was pronounced ready for surgery when analgesia was present in all areas to be operated upon , which always included the three nerves to the h and . The single injection technique required less time for block performance ( mean 5.5 min ) than multiple injections ( mean 9.5 min ) , P < 0.0001 . However , latency of the block was longer and the requirement for supplemental nerve blocks was greater , after single injections ( 33 min and 57 % ) than after multiple injections ( 15.5 min and 7 % , respectively ) , P < 0.0001 . As a result , readiness for surgery was achieved faster in group 2 ( 25 min ) , than in group 1 ( 38.5 min ) , P < 0.0001 . After supplementation , block effectiveness was 100 % in group 1 and 98 % in group 2 ( NS ) . The frequency of adverse effects ( vessel puncture or paraesthesia ) was similar in both groups . No neurological sequelae were observed . We conclude that the multiple injection technique takes longer to perform than single injection , but that readiness for surgery is faster because of shorter block latency and better spread of analgesia A perivascular catheter technique ( PVT ) and a nerve stimulator technique ( NST ) for axillary brachial plexus block were compared in terms of quality : complete , incomplete or failed blocks . In a r and omised series , 30 PVT blocks and 30 NST blocks were performed by three staff anaesthetists . In the NST group , surgical anaesthesia was always achieved , whereas in the PVT group , four blocks required supplementation with general anaesthesia . In both groups eight patients needed supplementation with addilioncd conduction blocks of 1–3 peripheral nerves . It is concluded that a nerve stimulator technique may increase the success rate of axillary brachial plexus block to some extent Background and Objectives . This study evaluates the effects of clonidine added to mepivacaine on the duration of anesthesia and analgesia after axillary brachial plexus block . Methods . Thirty patients scheduled for elective h and surgery were divided into three equal groups in a r and omized , double-blinded fashion . An axillary perivascular brachial plexus block was performed with 40 ml 1 % mepivacaine plus 1:200,000 epinephrine in the three groups . Group B also received 150 μg clonidine subcutaneously and Group C had the same dose of clonidine mixed with the local anesthetic and injected into the plexus sheath . The following variables were recorded : onset time , duration of anesthesia , duration of analgesia , postoperative pain score , intake of analgesics , and adverse effects . Results . The three groups were comparable in terms of age , sex , weight , height , onset time of anesthesia , postoperative pain score , and analgesic requirement . The duration of anesthesia and analgesia was comparable in Groups A and B , but both variables were significantly increased in Group C : the duration of anesthesia and analgesia were prolonged , respectively , by 37 ± 6 % and 103 ± 16 % when compared to Group A and by 32 ± 7 % and 89 ± 15 % when compared to Group B. No side effects were reported . Conclusions . One hundred fifty micrograms clonidine added to mepivacaine for brachial plexus block prolongs the duration of anesthesia and analgesia . Our results suggest that this effect of clonidine is local rather than systemic The goal of this double-blind prospect i ve study was to compare the effect of a single injection versus multiple fractionated doses on the onset time and quality of motor and sensory block , obtained in 70 children anaesthetized with axillary block alone . The brachial plexus was identified with a peripheral nerve stimulator , and blocked with 0.5 ml.kg-1 of 1.5 % lignocaine with adrenaline . In Group S ( single injection ) , the total volume was injected after location of one nerve . In Group M ( multiple fractionated doses ) , two nerves were located , including necessarily one nerve implicated in the surgical territory . Motor and sensory blocks were assessed according to Lanz 's scale before surgery by a blinded observer . A block was considered complete if there was no feeling in at least three nerve territories at 30 min . No difference was found between groups for motor and sensory block quality . However the onset time of the block was faster after multiple fractionated doses ( Group M , 25+/-7 min vs Group S , 29+/-4 min ) and was faster in younger children ( 5 - 9 years : M=23+/-7 min vs S=28+/-5 min , 10 - 15 years : no difference ) . There was a significant difference in the quality of the sensory blockade of the musculocutaneous nerve : 18 versus 8 complete blocks , 10 versus 14 incomplete blocks , respectively for Group M versus Group S. No adverse effect was observed and analgesia was prolonged for more than 4 h. We can conclude that , unlike adults , fractionated doses in chilren bring no benefit to the quality of sensory and motor block . Selective block of the musculocutaneous nerve is recommended when a surgical procedure takes place in this territory Background and Objectives Insufficient spread of the local anesthetic toward the retroarterial region of the neurovascular space may be responsible for inconsistent anesthesia of the upper limb after single-injection axillary block . We hypothesized that injection of the local anesthetic on a single radial-nerve stimulation would produce the same extent of anesthesia as either a single median-nerve stimulation , a double-stimulation technique ( radial and musculocutaneous nerves ) , or a triple-stimulation technique ( radial , musculocutaneous , and median nerves ) . Methods One hundred twenty patients were r and omly assigned to receive an axillary block by either median-nerve , radial-nerve , radial-nerve plus musculocutaneous-nerve , or triple-nerve stimulation with 40 mL of plain 1.5 % mepivacaine . Patients were assessed for sensory block by the pinprick method at 5 and 20 minutes . Results Radial-nerve stimulation produced more extensive anesthesia than did median-nerve stimulation . The rate of anesthesia at 20 minutes in the median-nerve cutaneous distribution was similar after median-nerve stimulation or radial-nerve stimulation . The ulnar nerve was more frequently blocked at 20 minutes after radial-nerve stimulation than after median-nerve stimulation . Extent of anesthesia at 20 minutes after radial-nerve plus musculocutaneous-nerve stimulation was similar to that produced by triple-nerve stimulation , except for lower rates of anesthesia that corresponded to the median nerve . All of the differences were statistically significant . Conclusions Musculocutaneous-nerve stimulation and radial-nerve stimulation play predominant roles in the success of axillary brachial plexus block , although a triple-nerve stimulation technique is still required to produce complete anesthesia of the upper limb BACKGROUND AND OBJECTIVES Axillary block using a single-injection method does not always provide effective analgesia . This study examined whether a double axillary block injection technique is superior to a single injection axillary block . METHOD Fifty patients were r and omly allocated to two groups . In group I ( single injection ) , the whole volume of local anesthetic ( 0.7 mL/kg ) was injected after locating only one of the median , radial , or ulnar nerves . In group 2 ( double injection ) , half of the volume was injected after locating one nerve and the other half after locating another peripheral nerve . Bupivacaine 0.5 % and prilocaine 1 % ( 1:1 volumes ) were used as local anesthetic . A peripheral nerve stimulator was used to identify the nerves . Sensory block of seven nerves and motor block of four nerves were tested after 40 minutes . RESULTS Complete sensory and motor block ( scores 2 or 3 on scale 0 - 3 ) in all four main nerves ( median , ulnar , radial , musculocutaneous ) was achieved in 3 ( 12 % ) versus 20 ( 80 % ) patients in groups 1 and 2 , respectively ( P = .000001 ) . Primary success rate ( no need for supplemental nerve block ) was 52 % in group 1 and 92 % in group 2 ( P = .0016 ) . CONCLUSIONS A double-injection method in axillary block provides excellent analgesia and motor block compared with a single-injection method . Moreover , the need for supplemental nerve blocks is significantly decreased STUDY OBJECTIVE To compare the extent of sensory and motor block with two different nerve stimulation techniques in axillary blocks . DESIGN Prospect i ve , r and omized , investigator-blinded study . SETTING Ambulatory surgery unit of a university hospital . PATIENTS 60 ASA physical status I , II , and III patients undergoing surgery at or below the elbow . INTERVENTIONS Patients receiving axillary block were r and omized into two nerve stimulation groups with either radial plus musculocutaneous or triple nerve stimulation ( radial , median , and musculocutaneous nerves ) . Thirty milliliters of plain 2 % mepivacaine was given to all patients either in a single or fractionated dosing for radial or for radial and median nerves , according to group assignment . Five milliliters of plain 1 % mepivacaine for the musculocutaneous nerve was given to all patients . MEASUREMENTS Blocks were assessed at 10 , 20 , and 30 minutes . Rates of supplementation given as a result of insufficient surgical anesthesia were also noted . MAIN RESULTS Statistically significantly higher rates of anesthesia at the cutaneous distributions of median and medial cutaneous of the arm nerves with multiple nerve stimulation at 30 minutes were found as compared with radial plus musculocutaneous nerve stimulation . The rate of supplementation was lower with multiple nerve stimulation . CONCLUSIONS Radial plus musculocutaneous nerve stimulation showed lower efficacy of axillary block than did triple nerve stimulation when using 2 % mepivacaine |
13,836 | 27,117,282 | Subgroup analyses suggest a more prominent effect for M1 stimulation .
Meta-regression revealed that a greater number of total stimulation pulses were associated with more UPDRS III improvements over the long-term .
The pooled evidence suggests that rTMS improves upper limb function in the short-term , walking performance and UPDRS III in the short- and long-terms in PD sufferers . | BACKGROUND The short-term beneficial effects of repetitive transcranial magnetic stimulation ( rTMS ) on motor signs in Parkinson 's disease ( PD ) have been addressed by previous meta-analyses while its long-term effects remain undetermined .
Although deterioration of walking and upper limb function greatly affects the participation in activities and quality of life of PD sufferers , the effect of rTMS thereon has not been systematic ally studied .
OBJECTIVE This systematic review aim ed to examine the efficacy of rTMS on improving physical function and motor signs over the short- and long-terms in people with PD . | We evaluated the effect of low-frequency rTMS on motor signs in Parkinson 's disease ( PD ) , under a double-blind placebo-controlled trial design . PD patients were r and omly assigned to received either real ( n = 9 ) or sham ( n = 9 ) rTMS for 10 days . Each session comprises two trains of 50 stimuli each delivered at 1 Hz and at 90 % of daily rest motor threshold using a large circular coil over the vertex . The effect of the stimulation , delivered during the ON-period , was evaluated during both ON and OFF periods . Tests were carried out before and after the stimulation period , and again 1 week after . The effect of the stimulation was evaluated through several gait variables ( cadence , step amplitude , velocity , the CV(stride-time ) , and the turn time ) , h and dexterity , and also the total and motor sections of the UPDRS . Only the total and motor section of the UPDRS and the turn time during gait were affected by the stimulation , the effect appearing during either ON or OFF evaluation , and most importantly , equally displayed in both real and sham group . The rest of the variables were not influenced . We conclude the protocol of stimulation used , different from most protocol s that apply larger amount of stimuli , but very similar to some previously reported to have excellent results , has no therapeutic value and should be ab and oned . This contrasts with the positive reported effects using higher frequency and focal coils . Our work also reinforces the need for sham stimulation when evaluating the therapeutic effect of rTMS OBJECTIVE Several studies have shown that repetitive transcranial magnetic stimulation ( rTMS ) over the dorsolateral prefrontal cortex ( DLPFC ) is effective in the treatment of depression in patients with Parkinson disease ( PD ) . However , since research into the effect of this type of rTMS regime on motor function is limited , we studied the effect of rTMS over the DLPFC on the motor functions in PD patients . METHODS Thirteen patients were r and omly assigned into 2 groups , one receiving real-rTMS ( 90 % of resting motor threshold , 10 Hz , 450 pulses-day for 10 consecutive days ) over the DLPFC contralateral to the more affected side , and the other group receiving sham-rTMS . Assessment included a clinical motor evaluation using part III of the Unified Parkinson 's Disease Rating Scale ( UPDRS ) , and several motor tasks . The UPDRS was applied before and after 10 days of rTMS . Finger tapping , reach movement , grip movement and gait were measured in each session before and after the rTMS over the 10 day period . RESULTS Statistical analysis ( ANOVA for repeated measures ; group * day * side * rTMS ) only showed a significant effect for finger tapping , reach movement and gait for the factor day . No significant change was reported for the UPDRS in any group . CONCLUSIONS Application of rTMS over the DLPFC as a 10 day course had no significant effect on motor functions and clinical motor status , and the improvement in performance of motor tasks can be attributed to the effects of practice . SIGNIFICANCE rTMS over the DLPFC did not lead to any motor improvement in PD patients Objective : To investigate the safety and efficacy of intermittent theta-burst stimulation ( iTBS ) in the treatment of motor symptoms in Parkinson disease ( PD ) . Background : Progression of PD is characterized by the emergence of motor deficits , which eventually respond less to dopaminergic therapy and pose a therapeutic challenge . Repetitive transcranial magnetic stimulation ( rTMS ) has shown promising results in improving gait , a major cause of disability , and may provide a therapeutic alternative . iTBS is a novel type of rTMS that may be more efficacious than conventional rTMS . Methods : In this r and omized , double-blind , sham-controlled study , we investigated safety and efficacy of iTBS of the motor and dorsolateral prefrontal cortices in 8 sessions over 2 weeks ( evidence Class I ) . Assessment of safety and clinical efficacy over a 1-month period included timed tests of gait and bradykinesia , Unified Parkinson 's Disease Rating Scale ( UPDRS ) , and additional clinical , neuropsychological , and neurophysiologic measures . Results : We investigated 26 patients with mild to moderate PD : 13 received iTBS and 13 sham stimulation . We found beneficial effects of iTBS on mood , but no improvement of gait , bradykinesia , UPDRS , and other measures . EEG/EMG monitoring recorded no pathologic increase of cortical excitability or epileptic activity . Few reported discomfort or pain and one experienced tinnitus during real stimulation . Conclusion : iTBS of the motor and prefrontal cortices appears safe and improves mood , but failed to improve motor performance and functional status in PD . Classification of evidence : This study provides Class I evidence that iTBS was not effective for gait , upper extremity bradykinesia , or other motor symptoms in PD Objective . To investigate the safety and efficacy of 50-Hz repetitive transcranial magnetic stimulation ( rTMS ) in the treatment of motor symptoms in Parkinson disease ( PD ) . Background . Progression of PD is characterized by the emergence of motor deficits that gradually respond less to dopaminergic therapy . rTMS has shown promising results in improving gait , a major cause of disability , and may provide a therapeutic alternative . Prior controlled studies suggest that an increase in stimulation frequency might enhance therapeutic efficacy . Methods . In this r and omized , double blind , sham-controlled study , the authors investigated the safety and efficacy of 50-Hz rTMS of the motor cortices in 8 sessions over 2 weeks . Assessment of safety and clinical efficacy over a 1-month period included timed tests of gait and bradykinesia , Unified Parkinson ’s Disease Rating Scale ( UPDRS ) , and additional clinical , neurophysiological , and neuropsychological parameters . In addition , the safety of 50-Hz rTMS was tested with electromyography-electroencephalogram ( EMG-EEG ) monitoring during and after stimulation . Results . The authors investigated 26 patients with mild to moderate PD : 13 received 50-Hz rTMS and 13 sham stimulation . The 50-Hz rTMS did not improve gait , bradykinesia , and global and motor UPDRS , but there appeared a short-lived “ on”-state improvement in activities of daily living ( UPDRS II ) . The 50-Hz rTMS lengthened the cortical silent period , but other neurophysiological and neuropsychological measures remained unchanged . EMG/EEG recorded no pathological increase of cortical excitability or epileptic activity . There were no adverse effects . Conclusion . It appears that 50-Hz rTMS of the motor cortices is safe , but it fails to improve motor performance and functional status in PD . Prolonged stimulation or other techniques with rTMS might be more efficacious but need to be established in future research Based on several open-label and case studies , repetitive transcranial magnetic stimulation ( rTMS ) seems to have an antidepressive effect on patients with Parkinson 's disease ( PD ) . However , this hypothesis requires further confirmation . We conducted a r and omized , double-blind placebo-controlled study to evaluate the effect of rTMS over the left dorsolateral prefrontal cortex ( DLPFC ) on depression and various motor and nonmotor features of PD . Twenty-two PD patients with mild or moderate depressive episodes were assigned into two groups , one receiving real-rTMS ( 90 % of resting motor threshold , 5 Hz , 600 pulses-a-day for 10 days ) over the left DLPFC , and another group receiving sham-rTMS . An investigator blinded to the treatment performed three video-taped examinations on each patient : before stimulation ( baseline ) , 1 day ( short term ) , and 30 days after treatment session ended ( long-term effect ) . Mini-Mental State Examination , Unified Parkinson 's Disease Rating Scale ( UPDRS ) , Hoehn-Yahr , Epworth Sleepiness , Visual Analog and Montgomery-Asberg Depression Rating Scales ( MADRS ) , Beck Depression Inventory ( BDI ) , and Trail making and Stroop tests were applied . In the actively treated group , not only depression rating scales showed significant improvement 30 days after treatment ended ( BDI by 44.4 % and MADRS by 26.1 % ) , but also the accuracy of Stroop test ( by 16 % ) . We could also demonstrate an insignificant improvement in UPDRS-III by 7.5 points ( 31.9 % , P = 0.06 ) . In the sham-treated group none of the examined tests and scales improved significantly after sham stimulation . Our study demonstrated the beneficial effect of the left DLPFC rTMS on depression in PD lasting at least 30 days after treatment . However , this result should be confirmed in patients with severe depression by further clinical trials The aim of the present study was to investigate the effects of one session of high-frequency repetitive transcranial magnetic stimulation ( rTMS ) applied over the left dorsal premotor cortex ( PMd ) and left dorsolateral prefrontal cortex ( DLPFC ) on choice reaction time in a noise-compatibility task , and cognitive functions in patients with Parkinson ’s disease ( PD ) . Clinical motor symptoms of PD were assessed as well . Ten patients with PD entered a r and omized , placebo-controlled study with a crossover design . Each patient received 10 Hz stimulation over the left PMd and DLPFC ( active stimulation sites ) and the occipital cortex ( OCC ; a control stimulation site ) in the OFF motor state , i.e. at least after 12 h of dopaminergic drugs withdrawal . Frameless stereotaxy was used to target the optimal position of the coil . For the evaluation of reaction time , we used a noise-compatibility paradigm . A short battery of neuropsychological tests was performed to evaluate executive functions , working memory , and psychomotor speed . Clinical assessment included a clinical motor evaluation using part III of the Unified Parkinson ’s Disease Rating Scale . Statistical analysis revealed no significant effect of rTMS applied over the left PMd and /or DLPFC in patients with PD in any of the measured parameters . In this study , we did not observe any effect of one session of high frequency rTMS applied over the left PMd and /or DLPFC on choice reaction time in a noise-compatibility task , cognitive functions , or motor features in patients with PD . rTMS applied over all three stimulated areas was well tolerated and safe in terms of the cognitive and motor effects Dysfunction of the basal ganglia-thalamocortical motor circuit is a fundamental model to account for motor symptoms in Parkinson 's disease ( PD ) . Using high-frequency repetitive transcranial magnetic stimulation ( rTMS ) over the supplementary motor area ( SMA ) , we investigated whether modulation of SMA excitability engenders therapeutic effects on motor symptoms in PD . In this double-blind placebo-controlled study , 99 patients were enrolled and assigned r and omly to SMA-stimulation and sham-stimulation groups . For SMA stimulation , 20 trains of 50 transcranial magnetic stimuli at 5 Hz were delivered at an intensity of 110 % active motor threshold for leg muscles in one session . The sham stimulation was 20 trains of electric stimuli given through electrodes fixed on the head to mimic the cutaneous sensation during rTMS . Each session of intervention was carried out once a week for the first 8 weeks . The SMA stimulation , in contrast to the sham stimulation , engendered significant improvements in total scores and motor scores of the Unified Parkinson 's Disease Rating Scale . Mean improvements in motor scores were 4.5 points in the SMA-stimulation group and -0.1 points in the sham-stimulation group . Results indicate that 5 Hz rTMS over SMA modestly improves motor symptoms in PD patients ; SMA is a potential stimulation site for PD treatment Dopamine is implicated in movement , learning , and motivation , and in illnesses such as Parkinson 's disease , schizophrenia , and drug addiction . Little is known about the control of dopamine release in humans , but research in experimental animals suggests that the prefrontal cortex plays an important role in regulating the release of dopamine in subcortical structures . Here we used [(11)C]raclopride and positron emission tomography to measure changes in extracellular dopamine concentration in vivo after repetitive transcranial magnetic stimulation ( rTMS ) of the dorsolateral prefrontal cortex in healthy human subjects . Repetitive TMS of the left dorsolateral prefrontal cortex caused a reduction in [(11)C]raclopride binding in the left dorsal cau date nucleus compared with rTMS of the left occipital cortex . There were no changes in binding in the putamen , nucleus accumbens , or right cau date . This shows that rTMS of the prefrontal cortex induces the release of endogenous dopamine in the ipsilateral cau date nucleus . This finding has implication s for the therapeutic and research use of rTMS in neurological and psychiatric disorders The neural mechanisms and circuitry involved in levodopa-induced dyskinesia are unclear . Using repetitive transcranial magnetic stimulation ( rTMS ) over the supplementary motor area ( SMA ) in a group of patients with advanced Parkinson disease , the authors investigated whether modulation of SMA excitability may result in a modification of a dyskinetic state induced by continuous apomorphine infusion . rTMS at 1 Hz was observed to markedly reduce drug-induced dyskinesias , whereas 5-Hz rTMS induced a slight but not significant increase The sequence effect ( SE ) in Parkinson 's disease ( PD ) is progressive slowing of sequential movements . It is a feature of bradykinesia , but is separate from a general slowness without deterioration over time . It is commonly seen in PD , but its physiology is unclear . We measured general slowness and the SE separately with a computer-based , modified Purdue pegboard in 11 patients with advanced PD . We conducted a placebo-controlled , four-way crossover study to learn whether levodopa and repetitive transcranial magnetic stimulation ( rTMS ) could improve general slowness or the SE . We also examined the correlation between the SE and clinical fatigue . Levodopa alone and rTMS alone improved general slowness , but rTMS showed no additive effect on levodopa . Levodopa alone , rTMS alone , and their combination did not alleviate the SE . There was no correlation between the SE and fatigue . This study suggests that dopaminergic dysfunction and abnormal motor cortex excitability are not the relevant mechanisms for the SE . Additionally , the SE is not a component of clinical fatigue . Further work is needed to establish the physiology and clinical relevance of the SE . © 2010 Movement Disorder Society It has been 30 years since the discovery that repeated electrical stimulation of neural pathways can lead to long-term potentiation in hippocampal slices . With its relevance to processes such as learning and memory , the technique has produced a vast literature on mechanisms of synaptic plasticity in animal models . To date , the most promising method for transferring these methods to humans is repetitive transcranial magnetic stimulation ( rTMS ) , a noninvasive method of stimulating neural pathways in the brain of conscious subjects through the intact scalp . However , effects on synaptic plasticity reported are often weak , highly variable between individuals , and rarely last longer than 30 min . Here we describe a very rapid method of conditioning the human motor cortex using rTMS that produces a controllable , consistent , long-lasting , and powerful effect on motor cortex physiology and behavior after an application period of only 20 - 190 Repetitive transcranial magnetic stimulation ( rTMS ) has been used as a potential therapeutic tool in Parkinson 's disease ( PD ) . However , the therapeutic value and /or the placebo effect of rTMS on PD remain to be eluci date d. To investigate the therapeutic value and /or placebo effect of rTMS in PD , we compared the motor section of unified PD rating scale ( UPDRS III ) and the amount of extracellular dopamine concentration using [ (11)C ] raclopride PET before and after two sessions of rTMS in 9 PD patients . During a consecutive 2 days while off-medication , two series of 15 trains of 5 Hz-frequency rTMS ( intensity , 90 % of the resting motor threshold ) were applied to the h and area of more severely symptomatic motor cortex ( MC ) . After unilateral rTMS of MC , mean raclopride binding potentials ( BPs ) were reduced not only in putaminal and cau date areas on the stimulated side ( -4.9 % and -6.5 % , respectively ) ( P > 0.05 ) but also in putaminal and cau date areas of nonstimulated hemispheres ( -6.6 % , P > 0.05 and -12.1 % , P = 0.049 , respectively ) . UPDRS III scores were significantly decreased ( 35.0 + /- 14.1 to 32.0 + /- 13.4 , P = 0.049 ) . A reduction of raclopride BP in nonstimulated ventral striatum by unilateral rTMS supports the placebo response during rTMS OBJECTIVES To evaluate the therapeutic potential of repetitive transcranial magnetic stimulation ( rTMS ) for Parkinson 's disease ( PD ) by delivering stimulation at higher intensity and frequency over longer time than in previous research . Promising beneficial effects on movement during or after rTMS have been reported . METHODS Ten patients with idiopathic PD were enrolled in a r and omized crossover study comparing active versus sham rTMS to the supplementary motor area ( SMA ) . Assessment s included reaction and movement times ( RT/MT ) , quantitative spiral analysis , timed motor performance tests , United Parkinson 's Disease Rating Scale ( UPDRS ) , patient self-report and guess as to stimulation condition . RESULTS Two of 10 patients could not tolerate the protocol . Thirty to 45 min following stimulation , active rTMS as compared with sham stimulation worsened spiral drawing ( P=0.001 ) and prolonged RT in the most affected limb ( P=0.030 ) . No other significant differences were detected . CONCLUSIONS We sought clinical ly promising improvement in PD but found sub clinical worsening of complex and preparatory movement following rTMS to SMA . These results raise safety concerns regarding the persistence of dysfunction induced by rTMS while supporting the value of rTMS as a research tool . Studies aim ed at underst and ing basic mechanisms and timing of rTMS effects are needed To study the efficacy of 0.2-Hz repetitive transcranial magnetic stimulation ( rTMS ) on Parkinson 's disease ( PD ) , 85 patients with PD were enrolled into three groups : 1 ) . motor cortical , 2 ) . occipital , and 3 ) . sham stimulation . A round coil was centered over the vertex in motor cortical stimulation , and over the inion in occipital stimulation . In one session , 100 stimuli of 0.2-Hz rTMS at an intensity of 1.1 times active motor threshold ( AMT ) were given . In sham stimulation , electric currents were given with electrodes fixed on the head to mimic the sensation in real stimulation . Each session was carried out once a week for the first 8 weeks . The Unified Parkinson Disease Rating Scale ( UPDRS ) , Hamilton Rating Scale for Depression ( HRSD ) and subjective score ( visual analogue scale ) were assessed . There were no significant differences in clinical features among the three groups . Total and motor score of UPDRS were improved to the same extent by rTMS over Cz , inion , and sham stimulation . HRSD was improved by rTMS over Cz and sham stimulation in the same manner . Subjective score was not significantly improved by any methods of stimulation . 0.2-Hz rTMS at an intensity of 1.1 x AMT has only a placebo effect on PD . Our realistic sham stimulation maneuver must produce powerful placebo effects as a real stimulation Background and Purpose : Relatively little is known about the natural evolution of physical activity – related participation restrictions associated with Parkinson 's disease ( PD ) . We examined this issue prospect ively , using continuous monitoring technology to capture the free-living ambulatory activity of persons with PD engaging in life situations . We specifically sought ( 1 ) to explore natural , long-term changes in daily ambulatory activity and ( 2 ) to compare the responsiveness of ambulatory activity parameters to clinical measures of gait and disease severity . Methods : Thirty-three persons with PD participated ( Hoehn and Yahr range of 1–3 ) . Participants wore a step activity monitor for up to 7 days at baseline and again at 1-year follow-up . Mean daily values were calculated for parameters indicative of amount , intensity , frequency , and duration of ambulatory activity . Clinical measures included the Unified Parkinson Disease Rating Scale , the 6-Minute Walk , and Maximal Gait Speed . Parametric tests for paired sample s were used to investigate changes in ambulatory activity parameters and clinical measures . Results : Participants had significant declines in the amount and intensity of daily ambulatory activity but not in its frequency and duration ( P < 0.007 ) . Declines occurred in the absence of changes in clinical measures of gait or disease severity . The greatest 1-year decline occurred in the number of daily minutes participants spent engaging in at least moderate-intensity ambulatory activity . Conclusion : Continuous monitoring of ambulatory activity beyond mere step counts may serve as a distinct and important means of quantifying declining ambulatory behavior associated with disease progression or improved ambulatory behavior result ing from rehabilitation and medical and /or surgical interventions in persons with PD OBJECTIVES Previous studies found that people with Parkinson 's disease ( PD ) walked at a slower speed and with significantly shorter stride length and /or increase in variability of stride length than control subjects . The present study aim ed to examine whether difference existed in amplitude and variability of step length between control and PD subjects if they walked at a similar speed . METHODS This was a cross-sectional study . Thirteen PD patients and 15 healthy control subjects were instructed to walk at a similar speed on a treadmill under 2 r and omized conditions : walking alone ( Walk(o ) ) and walking with digit subtraction of 3 ( Walk(calculation ) ) . Amplitude of step length ( cm ) , variability of step length ( % ) , and percent accuracy of the calculation task ( % ) were recorded and analysed . RESULTS During both Walk(o ) and Walk(calculation ) , PD patients had significantly shorter step length and larger step length variability than control subjects ( p<0.05 ) . When a cognitive task was added to walking , PD patients showed a significant decrease in step length without further change in step length variability ( p<0.05 ) . CONCLUSION As reduced step length persisted when the control subjects walked at a speed similar to that of patients , our finding suggests that PD patients had a fundamental problem in regulating the amplitude of step length during walking OBJECTIVE To assess the effects of focal motor cortex stimulation on motor performance and cortical excitability in patients with Parkinson 's disease ( PD ) . METHODS Repetitive transcranial magnetic stimulation ( rTMS ) was performed on the left motor cortical area corresponding to the right h and in 12 ' off-drug ' patients with PD . The effects of subthreshold rTMS applied at 0.5 Hz ( 600 pulses ) or at 10 Hz ( 2000 pulses ) using a ' real ' or a ' sham ' coil were compared to those obtained by a single dose of l-dopa . The assessment included a clinical evaluation by the Unified Parkinson 's Disease Rating Scale and timed motor tasks , and a neurophysiological evaluation of cortical excitability by single- and paired-pulse TMS techniques . RESULTS ' Real ' rTMS at 10 or 0.5 Hz , but not ' sham ' stimulation , improved motor performance . High-frequency rTMS decreased rigidity and bradykinesia in the upper limb contralateral to the stimulation , while low-frequency rTMS reduced upper limb rigidity bilaterally and improved walking . Concomitantly , 10 Hz rTMS increased intracortical facilitation , while 0.5 Hz rTMS restored intracortical inhibition . CONCLUSIONS Low- and high-frequency rTMS of the primary motor cortex lead to significant but differential changes in patients with PD both on clinical and electrophysiological grounds . The effects on cortical excitability were opposite to previous observations made in healthy subjects , suggesting a reversed balance of cortical excitability in patients with PD compared to normals . However , the underlying mechanisms of these changes remain to determine , as well as the relationship with clinical presentation and response to l-dopa therapy . SIGNIFICANCE The present study gives some clues to appraise the role of the primary motor cortex in PD . Clinical improvement induced by rTMS was too short-lasting to consider therapeutic application , but these results support the perspective of the primary motor cortex as a possible target for neuromodulation in PD OBJECTIVE To determine whether low-frequency repetitive transcranial magnetic stimulation ( rTMS ) may modulate l-DOPA-induced dyskinesia ( LID ) in dyskinetic Parkinson 's disease ( PD ) patients . LID is a severe motor complication in advanced PD patients . The neural mechanisms involved in LID are not clear , and it is apparent that both an excessive decrease in internal pallidus firing and a modification and overactivation of cortical motor and premotor areas are involved in its pathogenesis . METHODS Using low frequency 1Hz repetitive rTMS we investigated whether decrease of excitability of the supplementary motor area ( SMA ) may result in modification of LID in PD patients . Furthermore we tested whether it was possible to enhance and /or prolong the beneficial effects of the treatment with repeated sessions of stimulation . RESULTS We observed that 1Hz rTMS induced a transient reduction of dyskinesias . A single session of rTMS improved LID , while repeated sessions of stimulation failed to enhance and /or prolong the beneficial effects of the procedure , without causing motor deterioration or other adverse effects . CONCLUSIONS These results suggest that LID may depend on an increased excitability of the SMA . SIGNIFICANCE SMA rTMS is effective in reducing transiently LID , although can not yet be considered clinical ly useful Objective : To explore the efficacy and stimulation frequency dependence of repetitive transcranial magnetic stimulation ( rTMS ) over the supplementary motor area ( SMA ) in Parkinson disease ( PD ) . Methods : In this r and omized , double-blind , sham-controlled , multicenter study with a parallel design , a weekly intervention was performed 8 times . The effects were monitored up to 20 weeks . By central registration , participants were assigned to 1 of 3 arms of the study : low-frequency ( 1-Hz ) rTMS , high-frequency ( 10-Hz ) rTMS , and realistic sham stimulation . The primary end point was the score change of the Unified Parkinson 's Disease Rating Scale ( UPDRS ) part III from the baseline . Several nonmotor symptom scales such as the Hamilton Rating Scale for Depression , apathy score , and nonmotor symptoms question naire were defined as secondary end points . Results : Of the 106 patients enrolled , 36 were allocated to 1-Hz rTMS , 34 to 10-Hz rTMS , and 36 to realistic sham stimulation . Results show 6.84-point improvement of the UPDRS part III in the 1-Hz group at the last visit of the 20th week . Sham stimulation and 10-Hz rTMS improved motor symptoms transiently , but their effects disappeared in the observation period . Changes in nonmotor symptoms were not clear in any group . No severe adverse event was reported . Conclusions : The 1-Hz rTMS over the SMA was effective for motor , but not nonmotor , symptoms in PD . Level of evidence : This study provides Class I evidence that 1-Hz rTMS over the SMA is effective for motor symptoms in PD Parkinson ’s disease is a movement disorder whose principal symptoms are tremor , rigidity , bradykinesia and postural instability . Initially , drugs like l-dopa or dopaminergic agonists are able to control these symptoms , but with the progress of the disease these drugs become less effective . Previous studies have reported that repetitive transcranial magnetic stimulation ( rTMS ) can improve these motor symptoms . The objective of this study was to investigate the neural mechanisms through which 25 Hz rTMS may improve motor symptoms in Parkinson ’s disease . In a double-blind placebo-controlled study , we evaluated the effects of 25 Hz . rTMS in 10 Parkinson ’s disease patients . Fifteen rTMS sessions were performed over the primary cortex on both hemispheres ( one after the other ) during a 12-week period . The patients were studied using functional magnetic resonance imaging during performance of a simple tapping and a complex tapping task , 1 week before the administration of the first rTMS session and just after the last session . rTMS improved bradykinesia , while functional magnetic resonance imaging showed different cortical patterns in prefrontal cortex when patients performed the complex tapping test . Furthermore , the improvement in bradykinesia is associated with cau date nucleus activity increases in simple tapping . Finally , we observed a relative change in functional connectivity between the prefrontal areas and the supplementary motor area after rTMS . These results show a potential beneficial effect of repetitive transcranial magnetic stimulation on bradykinesia in Parkinson ’s disease which is substantiated by neural changes observed in functional magnetic resonance imaging We studied the short-term clinical effects of 10-Hz repetitive transcranial magnetic stimulation ( rTMS ) of the motor h and area contralateral to the more affected limb in 12 non-fluctuating , for at least 12 hours drug free patients with Parkinson 's disease ( PD ) . We investigated the efficacy of rTMS in combination with a levodopa challenge test design under double-blind , placebo controlled conditions . Significant reductions of UPDRS III motor scores showed the treatment conditions : placebo/rTMS , levodopa/sham stimulation and levodopa/rTMS . A more detailed evaluation of arm symptoms contralateral to the stimulated brain region showed even more pronounced effects for the three conditions . There were significant differences between the mean response of the UPDRS III arm scores to the four test conditions . In conclusion our study demonstrates short-term beneficial effects of 10-Hz rTMS on motor symptoms in PD patients . A release of endogenous dopamine in subcortical structures , i.e. putamen , in response to rTMS is the most likely mechanism of action Background . Focal single-session repetitive transcranial magnetic stimulation ( rTMS ) of the primary motor cortex has been cl aim ed to be capable of improving motor function in Parkinson 's disease . Objective . The authors sought to determine which type of rTMS protocol holds the highest potential for future therapeutic application . Methods . Twenty-two patients with Parkinson 's disease received 5 different rTMS protocol s on 5 consecutive days in a pseudor and omized and counterbalanced order either in the defined OFF condition or with their usual medication . The protocol s tested in the present study included 2 conventional rTMS protocol s ( 0.5 and 10 Hz ) as well as the recently introduced theta burst stimulation ( cTBS , iTBS ) and a sham condition . Cortical excitability , motor performance ( pointing movement , pronation-supination , Purdue Pegboard Test , walking ) , and mood were assessed before and after each session . Results . The authors observed motor training from days 1 to 4 , particularly in the group on dopaminergic medication . None of the rTMS paradigms excelled placebo stimulation . The only exception was the Purdue Pegboard Test , in which all active stimulation paradigms yielded slightly stronger effects than sham stimulation . Conclusions . Within a single session , no clinical ly relevant difference in the rTMS protocol s could be detected . Training effects outweigh and may have masked rTMS effects , particularly in the group on dopaminergic mediation BACKGROUND Repetitive transcranial magnetic stimulation ( rTMS ) has been reported to be clinical ly effective for treating motor symptoms in Parkinson 's disease ( PD ) . Few studies have been performed reporting the effects of rTMS on non-motor symptoms such as depression and apathy in PD . OBJECTIVE We assessed the effects of high-frequency ( HF ) rTMS over the primary motor ( M1 ) foot area on motor symptoms , depression and apathy scales , and sensory symptoms in PD . METHODS We investigated the efficacy of 3 consecutive days of HF-rTMS over the M1 foot area in 21 patients with PD using a r and omized , double-blind cross-over trial compared with sham stimulation . Motor effects were evaluated using the Unified Parkinson 's Disease Rating Scale part III ( UPDRS-III ) , the self- assessment motor score , the visual analog scale ( VAS ) , the 10-m walking test , and finger tapping . Non-motor effects were analyzed using the Montgomery Asberg Depression Rating Scale , the Apathy Scale , and quantitative sensory testing . RESULTS HF-rTMS significantly improved UPDRS-III ( P < 0.001 ) , VAS ( P < 0.001 ) , the walking test ( P = 0.014 ) , self- assessment motor score ( P = 0.010 ) , and finger tapping measurement ( P < 0.05 ) compared to sham stimulation . In contrast , no significant improvement was observed in depression and apathy scales . Consecutive days of rTMS did not significantly increase the improvement in motor symptoms . There were no adverse effects following rTMS on patients with PD . CONCLUSIONS We confirmed that HF-rTMS over the M1 foot area significantly improved motor symptoms in patients with PD . In addition , daily repeated stimulation was not significantly more effective than a single session of stimulation , but may be effective for maintaining the improvement in motor symptoms in patients with PD Abstract The therapeutic effect of repetitive transcranial magnetic stimulation ( rTMS ) on clinical performance was assessed by a double-blind study in 9 patients with Parkinson 's disease ( PD ) . Nine other patients underwent sham stimulation as controls . The modified Hoehn and Yahr ( H&Y ) staging scale , the Schwab and Engl and Activities of Daily Living ( ADL ) scale , and the Unified Parkinson 's disease rating scale ( UPDRS ) were used to assess changes of clinical performance . Patients were assessed prior to and following 2 months of rTMS . In addition , the mechanism of rTMS was investigated by dopamine and homovanillic acid ( HVA ) in the lumbar cerebrospinal fluid ( CSF ) of 17 patients before and after therapeutic rTMS for three or four months . rTMS was applied manually to the frontal areas 60 times per session , i. e. , 30 times per side using a large circular coil , a pulse intensity of 700 V , and a frequency of 0.2 Hz . Sessions were continued once a week for 2 months . The 9 control patients showed no changes of symptoms between the initial evaluation and that after 2 months of sham rTMS . In contrast , all 9 patients receiving rTMS showed a significant decrease of the modified H&Y and UPDRS scores after 2 months , while the Schwab and Engl and ADL Scale scores increased significantly . In the second CSF sample from patients receiving rTMS , HVA showed a significant decrease These results suggest that rTMS is beneficial for the symptoms of Parkinson 's disease and that it may act via inhibition of dopaminergic systems The purpose of this study was to investigate whether a period of continuous theta burst stimulation ( cTBS ) induces cortical plasticity and thus improves bradykinesia of the upper limb in Parkinson ’s disease . In eight patients with Parkinson ’s disease ( two females ; mean age : 68.5 ± 5 years ; disease duration : 4 ± 3 years ) electrophysiological ( motor evoked potentials , contralateral and ipsilateral silent period ) and behavioural ( Purdue pegboard test , UPDRS motor subscore ) parameters were evaluated before ( baseline condition ) and after a 40-s period of ( 1 ) real or ( 2 ) sham continuous theta burst stimulation over the primary motor cortex contralateral to the more affected body side off dopaminergic drugs . Compared to baseline , cTBS did change neither measures of cortical excitability nor behavioural measures . cTBS over the primary motor cortex does not impact on cortical excitability or motor function of the upper limb in Parkinson ’s disease . We interpret these data to reflect impaired cortical plasticity in Parkinson ’s disease . This study is an important contribution to the knowledge about impaired plasticity in Parkinson ’s disease Cortical excitability of the primary motor cortex is altered in patients with Parkinson 's disease ( PD ) . Therefore , modulation of cortical excitability by high frequency repetitive transcranial magnetic stimulation ( rTMS ) of the motor cortex might result in beneficial effects on motor functions in PD . The present study aims to evaluate the effect of rTMS of the motor cortex on motor functions in patients with PD . Thirty-six unmedicated PD patients were included consecutively in this study . The patients were assigned in a r and omized pattern to one of two groups , one group receiving real-rTMS ( suprathreshold 5-Hz , 2000 pulses once a day for 10 consecutive days ) and the second group receiving sham-rTMS using closed envelopes . Total motor section of Unified Parkinson 's Disease Rating Scale ( UPDRS ) , walking speed , and self- assessment scale were performed for each patient before rTMS and after the first , fifth , 10th sessions , and then after 1 month . Evaluation of these measures was performed blindly without knowing the type of rTMS . anova for repeated measurements revealed a significant time effect for the total motor UPDRS , walking speed and self- assessment scale during the course of the study in the group of patients receiving real-rTMS ( P = 0.0001 , 0.001 , and 0.002 ) , while no significant changes were observed in the group receiving sham-rTMS except in self- assessment scale ( P = 0.019 ) . A 10-day course of real-rTMS result ed in statistically significant long-term improvement of the motor functions in comparison with the sham-rTMS . The rTMS could have a therapeutic role of for PD patients The effect of focal 5 Hz repetitive transcranial magnetic stimulation ( rTMS ) of the motor h and area ( M1 ) on bradykinesia was studied in 12 unmedicated patients with Parkinson 's disease ( PD ) . On 2 separate days , a real-rTMS was applied to M1 contralaterally to the more severely affected limb or a frontal sham-rTMS was applied 3 cm anteriorly to Fz in a r and om order . Stimulus intensity was 10 % below resting motor threshold . Before and 20 min after rTMS , patients performed 15 consecutive pointing movements with the index finger contralaterally to the stimulated M1 . Compared with sham-rTMS , real-rTMS over the contralateral M1 caused a significant decrease in total movement time without affecting end-point accuracy . Our data provide evidence that 5 Hz rTMS over M1 can improve bradykinesia in PD patients beyond the time of magnetic stimulation Ten unmedicated patients with Parkinson 's disease received sub-threshold 5-Hz repetitive transcranial magnetic stimulation ( rTMS ) over the primary motor h and area ( M1(H AND ) ) contralaterally to the more affected upper limb . Compared to a midfrontal sham-rTMS , real-rTMS over M1(H AND ) was associated with a significant decrease in the global motor UPDRS score 1 h after the cessation of rTMS . This was mainly due to a clinical improvement in the arm contralaterally to the stimulated M1(H AND ) . These preliminary data suggest that focal rTMS of M1(H AND ) may have a therapeutic potential in PD Previous studies in patients with Parkinson 's disease have reported that a single session of repetitive transcranial magnetic stimulation ( rTMS ) can improve some or all of the motor symptoms for 30 to 60 minutes . A recent study suggested that repeated sessions of rTMS lead to effects that can last for at least 1 month . Here we report data that both confirm and extend this work . Fifty-five unmedicated PD patients were classified into four groups : two groups ( early and late PD ) received 25 Hz rTMS bilaterally on the motor arm and leg areas ; other groups acted as control for frequency ( 10 Hz ) and for site of stimulation ( occipital stimulation ) . All patients received six consecutive daily sessions ( 3,000 pulses for each session ) . The first two groups then received a further three booster sessions ( 3 consecutive days of rTMS ) after 1 , 2 , and 3 months , while the third group had only one additional session after the first month . Unified Parkinson 's Disease Rating Scale ( UPDRS ) , walking time , key-tapping speed , and self- assessment scale were measured for each patient before and after each rTMS session and before and after the monthly sessions . Compared to occipital stimulation , 25 Hz rTMS over motor areas improved all measures in both early and late groups ; the group that received 10 Hz rTMS improved more than the occipital group but less than the 25 Hz groups . The effect built up gradually during the sessions and was maintained for 1 month after , with a slight reduction in efficacy . Interestingly , the effect was restored and maintained for the next month by the booster sessions . We conclude that 25 Hz rTMS can lead to cumulative and long-lasting effects on motor performance Dyskinesias are one of the most frequent and disabling complications of the long-term treatment of Parkinson 's disease ( PD ) . Although the cause is not completely understood , it appears that an imbalance between excitatory and inhibitory inputs from the basal ganglia to the motor cortex leads to overactivation of motor and premotor areas . Overactivation of the supplementary motor area ( SMA ) has been observed in neuroimaging studies in dyskinetic PD patients . We investigated the effects of low-frequency repetitive transcranial magnetic stimulation ( rTMS ) of the SMA on levodopa-induced dyskinesias ( LID ) and motor performance in PD . We tested whether longer duration ( 10days ) and higher number of total pulses ( 1800 pulses ) would enhance the beneficial effect . Seventeen dyskinetic PD patients were r and omly assigned to real rTMS or sham ( placebo ) rTMS , and 1Hz rTMS or sham rTMS was applied over the SMA for 10 consecutive days . Patients were assessed at baseline and 1day after the last rTMS with a levodopa challenge test , and video recordings were taken . Dyskinesias and motor performance were rated off-line by two blinded raters using video recordings . After 10days of treatment with rTMS , we observed that 1Hz rTMS delivered over the SMA had decreased LID lasting for 24hours without a change in motor performance , whereas sham rTMS induced no significant change in dyskinesia scores . These results support a possible therapeutic effect of low-frequency rTMS in LID . However , in order to suggest rTMS as an effective treatment , long-term observations and further investigations with a larger patient population are essential In a placebo-controlled , single-blinded , crossover study , we assessed the effect of " real " repetitive transcranial magnetic stimulation ( rTMS ) versus " sham " rTMS ( placebo ) on peak dose dyskinesias in patients with Parkinson 's disease ( PD ) . Ten patients with PD and prominent dyskinesias had rTMS ( 1,800 pulses ; 1 Hz rate ) delivered over the motor cortex for 4 consecutive days twice , once real stimuli and once sham stimulation were used ; evaluations were done at the baseline and 1 day after the end of each of the treatment series . Direct comparison between sham and real rTMS effects showed no significant difference in clinician-assessed dyskinesia severity . However , comparison with the baseline showed small but significant reduction in dyskinesia severity following real rTMS but not placebo . The major effect was on dystonia subscore . Similarly , in patient diaries , although both treatments caused reduction in subjective dyskinesia scores during the days of intervention , the effect was sustained for 3 days after the intervention for the real rTMS only . Following rTMS , no side effects and no adverse effects on motor function and PD symptoms were noted . The results suggest the existence of residual beneficial clinical aftereffects of consecutive daily applications of low-frequency rTMS on dyskinesias in PD . The effects may be further exploited for potential therapeutic uses |
13,837 | 27,333,194 | Clear evidence emerged for the efficacy of cognitive behavioral therapy in promoting improvements in anxiety , depression , and quality of life .
CONCLUSION This is the first meta- analysis to demonstrate the efficacy of interventions on a range of psychosocial outcomes following breast cancer surgery .
The meta- analysis highlighted that cognitive behavioral therapy was consistently the most effective psychosocial intervention promoting improvements in anxiety , depression , and quality of life . | OBJECTIVE Breast cancer is the most commonly diagnosed cancer in women across the world .
The majority of women diagnosed with the disease undergo surgery , which is often associated with significant psychosocial morbidity .
The aim of this meta- analysis was to identify the efficacy of psychosocial interventions for women following breast cancer surgery . | Background Breast cancer among women is a relatively common with a more favorable expected survival rates than other forms of cancers . This study aim ed to determine the improved quality of life for post-mastectomy women through peer education . Methods Using pre and post test follow up and control design approach , 99 women with stage I and II of breast cancer diagnosis were followed one year after modified radical mastectomy . To measure the quality of life an instrument design ed by the European organization for research and treatment of cancer , known as the Quality of Life Question ( QLQ-30 ) and it 's breast cancer supplementary measure ( QLQ-BR23 ) at three points in time ( before , immediately and two months after intervention ) for both groups were used . The participant selection was a convenient sampling method and women were r and omly assigned into two experimental and control groups . The experimental group was r and omly assigned to five groups and peer educators conducted weekly educational programs for one month . Tabulated data were analyzed using chi square , t test , and repeated measurement multivariate to compare the quality of life differences over time . Results For the experimental group , the results showed statistically significant improvement in all performance aspects of life quality and symptom reduction ( P < 0.001 ) , while the control group had no significant differences in all aspects of life quality . Conclusion The findings of this study suggest that peer led education is a useful intervention for post-mastectomy women to improves their quality of life OBJECTIVE The aim is to evaluate the effectiveness of a manualized 12-week supportive-expressive group therapy program among primary breast cancer patients treated in community setting s , to determine whether highly distressed patients were most likely to benefit and whether therapist 's training or experience was related to outcome . METHOD Three hundred and fifty-three women within one year of diagnosis with primary breast cancer were r and omly assigned to receive supportive-expressive group therapy or to an education control condition . Participants were recruited from two academic centers and nine oncology practice s , which were members of NCI 's Community Clinical Oncology Program ( CCOP ) and were followed over 2 years . RESULTS A 2x2x19 analysis of variance was conducted with main effects of treatment condition , cohort , and baseline distress and their interactions . There was no main effect for treatment condition after removing one subject with an extreme score . Highly distressed women did not derive a greater benefit from treatment . Therapist training and psychotherapy experience were not associated with a treatment effect . CONCLUSIONS This study provides no evidence of reduction in distress as the result of a brief supportive-expressive intervention for women with primary breast cancer . Future studies might productively focus on women with higher initial levels of distress PURPOSE Evidence suggests that the re-entry phase ( ie , early period after medical treatment completion ) presents distinct challenges for cancer patients . To facilitate the transition to recovery , we conducted the Moving Beyond Cancer ( MBC ) trial , a multisite , r and omized , controlled trial of psychoeducational interventions for breast cancer patients . METHODS Breast cancer patients were registered within 6 weeks after surgery . After medical treatment , they completed baseline measures and were r and omly assigned to st and ard National Cancer Institute print material ( CTL ) ; st and ard print material and peer-modeling videotape ( VID ) ; or st and ard print material , videotape , two sessions with a trained cancer educator , and informational workbook ( EDU ) . Two primary end points were examined : energy/fatigue and cancer-specific distress . Secondary end points were depressive symptoms and post-traumatic growth . Perceived preparedness for re-entry was analyzed as a moderator of effects . RESULTS Of 558 women r and omly assigned to treatment , 418 completed the 6-month assessment and 399 completed the 12-month assessment . In analyses controlling for study site and baseline depressive symptoms , VID produced significant improvement in energy/fatigue at 6 months relative to CTL , particularly among women who felt less prepared for re-entry at baseline . No significant main effect of the interventions emerged on cancer-specific distress , but EDU prompted greater reduction in this outcome relative to CTL at 6 months for patients who felt more prepared for re-entry . Between-group differences in the primary outcomes were not significant at 12 months , and no significant effects emerged on the secondary end points . CONCLUSION A peer-modeling videotape can accelerate the recovery of energy during the re-entry phase in women treated for breast cancer , particularly among those who feel less prepared for re-entry OBJECTIVES Considerable morbidity persists among survivors of breast cancer ( BC ) including high levels of psychological stress , anxiety , depression , fear of recurrence , and physical symptoms including pain , fatigue , and sleep disturbances , and impaired quality of life . Effective interventions are needed during this difficult transitional period . METHODS We conducted a r and omized controlled trial of 84 female BC survivors ( Stages 0-III ) recruited from the H. Lee Moffitt Cancer and Research Institute . All subjects were within 18 months of treatment completion with surgery and adjuvant radiation and /or chemotherapy . Subjects were r and omly assigned to a 6-week Mindfulness-Based Stress Reduction ( MBSR ) program design ed to self-regulate arousal to stressful circumstances or symptoms ( n=41 ) or to usual care ( n=43 ) . Outcome measures compared at 6 weeks by r and om assignment included vali date d measures of psychological status ( depression , anxiety , perceived stress , fear of recurrence , optimism , social support ) and psychological and physical subscales of quality of life ( SF-36 ) . RESULTS Compared with usual care , subjects assigned to MBSR(BC ) had significantly lower ( two-sided p<0.05 ) adjusted mean levels of depression ( 6.3 vs 9.6 ) , anxiety ( 28.3 vs 33.0 ) , and fear of recurrence ( 9.3 vs 11.6 ) at 6 weeks , along with higher energy ( 53.5 vs 49.2 ) , physical functioning ( 50.1 vs 47.0 ) , and physical role functioning ( 49.1 vs 42.8 ) . In stratified analyses , subjects more compliant with MBSR tended to experience greater improvements in measures of energy and physical functioning . CONCLUSIONS Among BC survivors within 18 months of treatment completion , a 6-week MBSR(BC ) program result ed in significant improvements in psychological status and quality of life compared with usual care PURPOSE / OBJECTIVES To find the most effective methods of providing social support for women diagnosed with breast cancer by testing the effectiveness of a telephone social support and education intervention to promote emotional and interpersonal adaptation to breast cancer . DESIGN Multisite , two-group experimental study with repeated measures . SETTING Arkansas and New Jersey . SAMPLE The Arkansas sample consisted of 106 women who entered the study two to four weeks postsurgery for nonmetastatic breast cancer and were r and omly assigned to an experimental or control group . The comparison group consisted of 91 women from New Jersey who had participated in a previously completed study that used the same interventions and found that telephone support result ed in more positive , statistically significant adaptation to the disease . METHODS The experimental group received 13 months of telephone social support and education . Both groups received educational material s via a mailed re source kit . The Profile of Mood States ; Visual Analogue Scale-Worry ; Relationship Change Scale ; University of California , Los Angeles , Loneliness Scale-Version 3 ; and the modified Symptom Distress Scale provided data regarding the variables of interest . Data analysis included descriptive statistics , t tests , and multivariate analysis of variance with repeated measures . MAIN RESEARCH VARIABLES Mood , worry , relationships with significant others , loneliness , and symptoms . FINDINGS Data analysis showed no significant differences between groups , and both improved on some of the outcomes . Significant time-by-location interaction effects were found when comparing the Arkansas and New Jersey sample s , thereby supporting the need to consider regional differences when developing interventions . CONCLUSIONS The mailed educational re source kit alone appeared to be as effective as the telephone social support provided by oncology nurses in conjunction with the mailed re source kit . IMPLICATION S FOR NURSING Mailed educational re source kits may be the most efficient and cost-effective way to provide educational support to newly diagnosed patients with breast cancer , but their effect may differ according to region Abstract Background : This study aims to evaluate the effects of Group Cognitive Behavioral Therapy ( GCBT ) in treating major depression in Chinese women with breast cancer . Methods : Sixty-two breast cancer patients diagnosed with major depression were r and omly assigned to GCBT group ( N = 31 ) or a waiting list control group provided with an educational booklet ( N = 31 ) . The primary outcome measure was the 17-Item Hamilton Depression Rating Scale ( 17-HAMD ) . The second outcome measures were Self-Rating Anxiety Scale , Functional Assessment of Cancer Therapy – Breast and Self-Esteem Scale ( SES ) . Assessment s were carried out at completion of the study and six-month afterwards . Results : Patients in the GCBT group had a significant reduction in the 17-HAMD mean score by 9 points ( p < 0.001 ) , more than any reduction among patients in the control group from baseline to the end of therapy and a significant 7 points ( p < 0.001 ) more reduction from baseline to six-month follow-up . GCBT also yielded significantly greater improvement than the control group with regard to quality of life ( QoL ; p < 0.01 ) and self-esteem ( p < 0.05 ) . No significant differences were found between groups on improving anxiety ( p > 0.05 ) . Conclusion : The results of this trial suggest that GCBT is effective for treating major depression , as well as for improving QoL and self-esteem in breast cancer patients . Trial Registration : Chictr.org Background Among underserved , largely minority women who were breast cancer survivors , this pilot project was design ed to evaluate the quality of life outcomes of a 20 week Contemplative Self-Healing Program . Methods Women previously treated for stage I-III breast cancer were assessed before and after the 20 week program with the FACT-G , FACT-B , FACIT-Spirituality , ECOG , and the Impact of Events Scale . They participated in a 20-week intervention involving guided meditation and cognitive-affective-behavioral learning . Results With an average age of 63 , 62 % of the participants were African-American or Latino . With an average of 5.4 years since the diagnosis of breast cancer , 72 % had an ECOG performance status of 1 . 57 % were currently working . Their baseline FACT-G was 80.5 ± 15.1 , and their baseline Impact of Events Scale was 26.3 ± 18.9 . The within-patient improvement on the FACT-G was 4.6 ± 10.9 ( p = .01 ) ; in parallel the FACT-B improved by 2.8 ± 12.8 points ( p = .03 ) . The Impact of Events Scale improved by 6.6 ± 15.5 points ( p = .01 ) . There was significant within-patient improvement on both the avoidance scale ( 3.8 ± 9.2 ) and on the intrusion scale ( 2.9 ± 7.9 ) . Patients who attended more sessions and conducted more home practice had greater improvements in quality of life . Conclusion Persons receiving a 20-session contemplative self healing intervention showed improved quality of life , with a clinical ly and statistically significant increase in the FACT-G. In addition , this population showed a significant reduction in post-traumatic stress symptoms assessed by the Impact of Events Scale . Trial registration Clinical Trials Gov NCT00278837 A prospect i ve study was conducted to measure anxiety and depression in Iranian breast cancer patients before and after diagnosis using the Hospital Anxiety and Depression Scale ( HADS ) . The HADS was administered at two points in time : before diagnosis and 3 months after . In all , 168 breast cancer patients were interviewed . While 48 % of patients had severe symptoms of anxiety at both baseline and follow-up , more than 60 % of patients had no symptoms of depressive illness at pre- and post-diagnosis assessment s. Comparing anxiety and depression before diagnosis and after 3 months , there were no significant differences between patients ' scores on anxiety ( P = 0.42 ) and depression ( P = 0.98 ) subscales . The results showed that patients with advanced disease and a lower performance status were more anxious and experienced more depression . The study findings suggest that severe symptoms of anxiety are the most frequent symptoms in Iranian breast cancer patients . It seems that during the process of diagnosis and 3 months after psychological morbidity persists in patients who suffer from breast cancer PURPOSE Chronic insomnia is highly prevalent in cancer patients . Cognitive-behavioral therapy ( CBT ) is considered the treatment of choice for chronic primary insomnia . However , no r and omized controlled study has been conducted on its efficacy for insomnia secondary to cancer . Using a r and omized controlled design , this study conducted among breast cancer survivors evaluated the effect of CBT on sleep , assessed both subjectively and objective ly , and on hypnotic medication use , psychological distress , and quality of life . PATIENTS AND METHODS Fifty-seven women with insomnia caused or aggravated by breast cancer were r and omly assigned to CBT ( n = 27 ) or a waiting-list control condition ( n = 30 ) . The treatment consisted of eight weekly sessions administered in a group and combined the use of stimulus control , sleep restriction , cognitive therapy , sleep hygiene , and fatigue management . Follow-up evaluations were carried out 3 , 6 , and 12 months after the treatment . RESULTS Participants who received the insomnia treatment had significantly better subjective sleep indices ( daily sleep diary , Insomnia Severity Index ) , a lower frequency of medicated nights , lower levels of depression and anxiety , and greater global quality of life at post-treatment compared with participants of the control group after their waiting period . Results were more equivocal on polysomnographic indices . Therapeutic effects were well maintained up to 12 months after the intervention and generally were clinical ly significant . CONCLUSION This study supports the efficacy of CBT for insomnia secondary to breast cancer The evidence suggests that medical treatment of breast cancer produces psychosocial trauma in both the patient and her husb and due to the loss of the breast and /or physical disfigurement . This study evaluated the effects of a structured couples treatment program on the psychosocial discomfort following a mastectomy . Twenty couples were r and omly assigned to experimental and control conditions and were administered an assessment battery before and after treatment that measured change in marital happiness , sexual satisfaction , depression , self-esteem , helplessness , anxiety , alienation , and emotional discomfort . An analysis of variance yielded no significant difference between experimental and control conditions on any of the dependent variables . A supplemental analysis of covariance using the pretest as a covariate found that the treatment reduced emotional discomfort in both partners , reduced depression in the patient , and increased sexual satisfaction for both spouses . Recommendations were made for further study of the treatment , controlling for the subject 's level of distress prior to treatment BACKGROUND : Breast cancer is the most common cancer in women . Surgical treatment of breast cancer may cause body image alterations . The purpose of the current study was to examine the effects of cognitive behavioral counseling on body image among Iranian women with primary breast cancer . METHODS : In this quasi-experimental design ed study , 72 patients diagnosed as breast cancer and surgically treated were enrolled in Isfahan , Iran . The patients were entered the study by convenience sampling method and were r and omly divided in two groups of intervention ( n = 32 ) and control ( n = 40 ) . The intervention group received consultation based on Ellis rational emotive behavior therapy ( REBT ) method for 6 sessions during 3 weeks . The control group did not receive any consultation Paired t-test was used to compare the changes in groups and independent t-test was conducted to compare two groups . The average values represented as mean ± st and ard deviation . RESULTS : Before the study , the body image score was not significantly different between the intervention ( 16 97 ± 5 44 ) and control ( 15 95 ± 4 66 ) groups ( t = 0 86 , P = 0 395 ) . The body image score was significantly lower in the interven-tion group ( 9 03 ± 6 11 ) compared to control group ( 17 18 ± 5 27 ) after the intervention ( t = -6 07 , P < 0 001 ) . CONCLUSIONS : Since a woman 's body image influences her breast cancer treatment decision , oncology professionals need to recognize the value of a woman 's favorite about appearance and body image . This study emphasizes the importance of offering consultation in breast cancer patients OBJECTIVE Patients with breast cancer experience unmet informational and psychosocial needs at the end of treatment . A brief psychoeducational intervention delivered at this transition may help to address some of the challenges these women face . The purpose of this study was to test the effectiveness of a single-session group psychoeducational intervention ( GBOT group ) compared with st and ard print material ( usual care ) . METHODS In this r and omized controlled trial , 442 patients with breast cancer who were completing their adjuvant radiotherapy were recruited and r and omized to receive either usual care , which includes st and ard print material ( CRL group n = 226 ) or usual care and the GBOT group intervention ( INT group n = 216 ) . Participants completed measures at baseline and again at 3 and 6 months post-intervention . RESULTS The INT group showed significant improvement in their knowledge regarding the re-entry transition period ( d = 0.31 ) and in their feelings of preparedness for re-entry ( d = 0.37 ) . There were no differences between the groups over time on health-related distress or mood . CONCLUSIONS Results support the effectiveness of providing a single-session group psychoeducational intervention as a first-step approach to supportive care for women at the end of breast cancer treatment PURPOSE / OBJECTIVES To examine the effectiveness of a psychoeducational intervention on quality of life ( QOL ) in breast cancer survivors in post-treatment survivorship . DESIGN A r and omized controlled trial . SETTING An academic center collaborating with a regional cancer center in the southeastern United States . SAMPLE 256 breast cancer survivors . METHODS Women were r and omly assigned to the experimental or wait control group . The Breast Cancer Education Intervention ( BCEI ) study was delivered in three face-to-face sessions and five monthly follow-up sessions ( three by telephone and two in person ) . The control group received four monthly attention control telephone calls and the BCEI at month 6 . Data were collected at baseline , three and six months after the BCEI for the experimental group , and one month after the BCEI ( at month 7 ) for the wait control group . MAIN RESEARCH VARIABLES Primary endpoints were overall QOL and physical , psychological , social , and spiritual well-being . FINDINGS No differences in QOL were reported at baseline between groups . The experimental group reported improved QOL at three months , whereas the wait control group reported a significant decline in QOL . The experimental group reported continued maintenance of QOL at six months . Although the wait control group reported improved QOL at six months , significant differences continued to exist between the groups . CONCLUSIONS The BCEI was an effective intervention in improving QOL during the first year of breast cancer survivorship . Treatment effects were durable over time . IMPLICATION S FOR NURSING Post-treatment survivorship has not been empirically studied to a large degree . The BCEI is one of the few interventions demonstrating effectiveness among survivors after primary treatment , suggesting that oncology nurses may be uniquely positioned to provide safe passage using education and support BACKGROUND A diagnosis of breast cancer and treatment are psychologically stressful events , particularly over the first year after diagnosis . Women undergo many dem and ing and anxiety-arousing treatments such as surgery , radiation and chemotherapy . Psychosocial interventions that promote psychosocial adaptation to these challenges may modulate physiological processes ( neuroendocrine and immune ) that are relevant for health outcomes in breast cancer patients . METHODS Women with Stages 1 - 3 breast cancer recruited 4 - 8 weeks after surgery were r and omized to either a 10-week group-based cognitive behavioral stress management ( CBSM ) intervention or a 1-day psychoeducational control group and completed question naires and late afternoon blood sample s at study entry and 6 and 12 months after assignment to experimental condition . RESULTS Of 128 women initially providing psychosocial question naire and blood sample s at study entry , 97 provided complete data for anxiety measures and cortisol analysis at all time points , and immune assays were run on a subset of 85 of these women . Those assigned to a 10-week group-based CBSM intervention evidence d better psychosocial adaptation ( lower reported cancer-specific anxiety and interviewer-rated general anxiety symptoms ) and physiological adaptation ( lower cortisol , greater Th1 cytokine [ interleukin-2 and interferon-gamma ] production and IL-2:IL-4 ratio ) after their adjuvant treatment compared to those in the control group . Effects on psychosocial adaptation indicators and cortisol appeared to hold across the entire 12-month observation period . Th1 cytokine regulation changes held only over the initial 6-month period . CONCLUSIONS This intervention may have facilitated a " recovery or maintenance " of Th1 cytokine regulation during or after the adjuvant therapy period . Behavioral interventions that address dysregulated neuroendocrine function could play a clinical ly significant role in optimizing host immunologic resistance during a vulnerable period PURPOSE To examine effects of music therapy and progressive muscle relaxation training on depression , anxiety and length of hospital stay in Chinese female breast cancer patients after radical mastectomy . METHODS A total of 170 patients were r and omly allocated to the intervention group ( n = 85 ) receiving music therapy and progressive muscle relaxation training plus routine nursing care and the control group ( n = 85 ) receiving routine nursing care . Music therapy and progressive muscle relaxation training were performed twice a day within 48 h after radical mastectomy , once in the early morning ( 6a.m.-8a.m . ) and once in the evening ( 9p.m.-11p.m . ) , for 30 min per session until discharged from the hospital . RESULTS A general linear model with univariate analysis showed that the intervention group patients had significant improvement in depression and anxiety in the effects of group ( F = 20.31 , P < 0.001 ; F = 5.41 , P = 0.017 ) , time ( F = 56.64 , P < 0.001 ; F = 155.17 , P < 0.001 ) and group*time interaction ( F = 6.91 , P = 0.009 ; F = 5.56 , P = 0.019 ) . The intervention group patients had shorter length of hospital stay ( 12.56 ± 1.03 ) than that of the control group ( 17.01 ± 2.46 ) with statistical significance ( F = 13.36 , P < 0.001 ) . CONCLUSION Music therapy and progressive muscle relaxation training can reduce depression , anxiety and length of hospital stay in female breast cancer patients after radical mastectomy 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 OBJECTIVE To investigate whether frequent hospital follow-up in the first year after breast cancer treatment might partly be replaced by nurse-led telephone follow-up without deteriorating health-related quality of life ( HRQoL ) , and whether a short educational group programme ( EGP ) would enhance HRQoL. PATIENTS AND METHODS A multicentre pragmatic r and omised controlled trial ( RCT ) with a 2 × 2 factorial design was performed among 320 breast cancer patients who were treated with curative intent . Participants were r and omised to follow-up care as usual ( 3-monthly outpatient clinic visits ) , nurse-led telephone follow-up , or the former strategies combined with an educational group programme . The primary outcome for both interventions was HRQoL , measured by EORTC QLQ-C30 . Secondary outcomes were role and emotional functioning and feelings of control and anxiety . RESULTS Data of 299 patients were available for evaluation . There was no significant difference in HRQoL between nurse-led telephone and hospital follow-up at 12 months after treatment ( p = 0.42 ; 95 % confidence interval ( CI ) for difference : -1.93 - 4.64 ) and neither between follow-up with or without EGP ( p = 0.86 ; 95 % CI for difference : -3.59 - 3.00 ) . Furthermore , no differences between the intervention groups and their corresponding control groups were found in role and emotional functioning , and feelings of control and anxiety ( all p-values > 0.05 ) . CONCLUSION Replacement of most hospital follow-up visits in the first year after breast cancer treatment by nurse-led telephone follow-up does not impede patient outcomes . Hence , nurse-led telephone follow-up seems an appropriate way to reduce clinic visits and represents an accepted alternative strategy . An EGP does not unequivocally affect positive HRQoL outcomes The aim of the study was to compare and evaluate a multidisciplinary educational programme with traditional follow-up visits to a physician after breast cancer surgery in terms of well-being , aspects of self-care and coping ability 1 year after diagnosis . A reduction in the intensity of follow-up after breast cancer surgery is recommended . New follow-up models are being debated and could be of interest . The study design was non-r and omised and comparative . Ninety-six consecutively selected women with newly diagnosed breast cancer , classified as stage I or stage II , participated in either a multidisciplinary educational programme ( n=50 ) , or traditional follow-up by a physician ( n=46 ) . Three question naires were used : Functional Assessment of Cancer Therapy-General ( FACT-G ) , a study specific question naire regarding self-care aspects ( SCA ) and Sense of Coherence ( SOC ) . With the exception of physical well-being at baseline there was no significant difference between the groups . The women in the multidisciplinary educational programme increased their physical and functional well-being ( P<0.01 ) . The women in traditional follow-up by a physician increased their functional well-being while social/family well-being ( P<0.01 ) decreased over time . There was a statistically significant difference in SOC ( P<0.001 ) in the traditional follow-up by a physician between baseline ( mean=74.4 , SD=12.4 ) and the 1-year follow up ( mean=67.7 , SD=11.4 ) . Thus , women in the traditional follow-up by a physician scored lower in the area of SOC 1 year after diagnosis . A multidisciplinary educational programme may be an alternative to traditional follow-up by a physician after breast cancer surgery , but more research is needed about the financial benefits and effectiveness of such a programme OBJECTIVE To determine whether a telephone counseling program can improve psychosocial outcomes among breast cancer patients post-treatment . METHODS A r and omized trial was conducted involving 21 hospitals and medical centers , with assessment s ( self-administered question naires ) at baseline , 12 and 18 months post-enrollment . Eligibility criteria included early stage diagnosis , enrollment during last treatment visit , and the ability to receive the intervention in English . Endpoints included distress ( Impact of Event Scale ) , depression ( Center for Epidemiologic Studies Depression Scale ) , and two study -specific measures : sexual dysfunction and personal growth . The control group ( n=152 ) received a re source directory for breast cancer ; the intervention group ( n=152 ) also received a one-year , 16 session telephone counseling program augmented with additional print material s. RESULTS Significant intervention effects were found for sexual dysfunction at 12 ( p=0.03 ) and 18 months ( p=0.04 ) and personal growth ( 12 months : p=0.005 ; 18 months : p=0.03 ) . No differences by group were found in mean scores for distress and depression , with both groups showing significant improvement at 12 and 18 months ( all p values for within-group change from baseline were < or=0.003 ) . However , when dichotomized at cutpoints suggestive of the need for a clinical referral , the control group showed virtually no change at 18 months , whereas the intervention group showed about a 50 % reduction in both distress ( p=0.07 ) and depression ( p=0.06 ) . CONCLUSIONS Telephone counseling may provide a viable method for extending psychosocial services to cancer survivors nationwide OBJECTIVE Greater mental health symptomatology of Latina breast cancer ( LBC ) patients along with the paucity of intervention trials to reduce distress underscores the scientific and practice gaps in comprehensive care . This trial investigated the effect of a paraprofessionally delivered , telephonic-based psycho-educational intervention on depressive symptoms among LBC patients . METHODS Latina breast cancer patients were recruited from the California Cancer Registry , hospital registries , and support groups . Participants were r and omly assigned to the intervention or control condition . The primary outcome was level of depressive symptoms as measured by the Center for Epidemiological Studies Depression scale . RESULTS One hundred ninety-nine LBC patients ( 84 English language preferred and 115 Spanish language preferred ) participated . The overall trial outcomes demonstrated a statistically significant decrease in depressive symptoms among LBC patients in the intervention condition compared with LBC patients in the control condition , after controlling for depressive symptoms at T1 and language ( p < 0.05 ) . At follow-up , 63 % of intervention LBC patients reported at least a five-point decrease in symptoms compared with 26 % of control LBC patients ( p < 0.05 ) . English language -preferred and Spanish language -preferred LBC patients in the intervention condition showed approximately an eight-point mean decrease in depressive symptoms from baseline ( M = 23.5 and M = 26.6 , respectively ) to follow-up ( M = 15.7 and M = 18.4 , respectively ) ( p < 0.001 ) , whereas those in the control condition showed no significant change . CONCLUSIONS Results demonstrate the effectiveness of a culturally responsive , paraprofessionally delivered intervention to reduce depressive symptoms among LBC patients . Therefore , community oncology practice s can affiliate with trained paraprofessionals to implement mental health services to address distress among our growing and increasingly ethnically , linguistically , and economically diverse oncology patient population PURPOSE To assess the effectiveness of mindfulness-based stress reduction ( MBSR ) for mood , breast- and endocrine-specific quality of life , and well-being after hospital treatment in women with stage 0 to III breast cancer . PATIENTS AND METHODS A r and omized , wait-listed , controlled trial was carried out in 229 women after surgery , chemotherapy , and radiotherapy for breast cancer . Patients were r and omly assigned to the 8-week MBSR program or st and ard care . Profile of Mood States ( POMS ; primary outcome ) , Functional Assessment of Cancer Therapy-Breast ( FACT-B ) , Functional Assessment of Cancer Therapy-Endocrine Symptoms ( FACT-ES ) scales and the WHO five-item well-being question naire ( WHO-5 ) evaluated mood , quality of life , and well-being at weeks 0 , 8 , and 12 . For each outcome measure , a repeated- measures analysis of variance model , which incorporated week 0 measurements as a covariate , was used to compare treatment groups at 8 and 12 weeks . RESULTS There were statistically significant improvements in outcome in the experimental group compared with control group at both 8 and 12 weeks ( except as indicated ) for POMS total mood disturbance ( and its subscales of anxiety , depression [ 8 weeks only ] , anger [ 12 weeks only ] , vigor , fatigue , and confusion [ 8 weeks only ] ) , FACT-B , FACT-ES , ( and Functional Assessment of Cancer Therapy subscales of physical , social [ 8 weeks only ] , emotional , and functional well-being ) , and WHO-5 . CONCLUSION MSBR improved mood , breast- and endocrine-related quality of life , and well-being more effectively than st and ard care in women with stage 0 to III breast cancer , and these results persisted at three months . To our knowledge , this study provided novel evidence that MBSR can help alleviate long-term emotional and physical adverse effects of medical treatments , including endocrine treatments . MBSR is recommended to support survivors of breast cancer |
13,838 | 30,215,706 | Overall , AQPA showed a strong inverse relationship with mortality and predictive utility when combined with established risk scores , and prognostic roles in morbidity , predicting cognitive function , New York Heart Association functional class and intercurrent events ( e.g. hospitalisation ) , but weak relationships with health-related quality of life scores .
AQPA has a strong prognostic role in CHF .
Big data and machine learning strategies will potentially yield better predictive value of AQPA in CHF patients | Actigraphy is increasingly incorporated into clinical practice to monitor intervention effectiveness and patient health in congestive heart failure ( CHF ) .
We explored the prognostic impact of actigraphy-quantified physical activity ( AQPA ) on CHF outcomes . | The purpose of this study was to develop a new two-regression model relating Actigraph activity counts to energy expenditure over a wide range of physical activities . Forty-eight participants [ age 35 yr ( 11.4 ) ] performed various activities chosen to represent sedentary , light , moderate , and vigorous intensities . Eighteen activities were split into three routines with each routine being performed by 20 individuals , for a total of 60 tests . Forty-five tests were r and omly selected for the development of the new equation , and 15 tests were used to cross-vali date the new equation and compare it against already existing equations . During each routine , the participant wore an Actigraph accelerometer on the hip , and oxygen consumption was simultaneously measured by a portable metabolic system . For each activity , the coefficient of variation ( CV ) for the counts per 10 s was calculated to determine whether the activity was walking/running or some other activity . If the CV was < or=10 , then a walk/run regression equation was used , whereas if the CV was > 10 , a lifestyle/leisure time physical activity regression was used . In the cross-validation group , the mean estimates using the new algorithm ( 2-regression model with an inactivity threshold ) were within 0.75 metabolic equivalents ( METs ) of measured METs for each of the activities performed ( P > or= 0.05 ) , which was a substantial improvement over the single-regression models . The new algorithm is more accurate for the prediction of energy expenditure than currently published regression equations using the Actigraph accelerometer BACKGROUND Risk stratification of patients with end-stage congestive heart failure is a critical component of the transplant c and i date selection process . Accurate identification of individuals most likely to survive without a transplant would facilitate more efficient use of scarce donor organs . METHODS AND RESULTS Multivariable proportional hazards survival models were developed with the use of data on 80 clinical characteristics from 268 ambulatory patients with advanced heart failure ( derivation sample ) . Invasive and noninvasive models ( with and without catheterization-derived data ) were constructed . A prognostic score was determined for each patient from each model . Stratum-specific likelihood ratios were used to develop three prognostic-score risk groups . The models were prospect ively vali date d on 199 similar patients ( validation sample ) by calculation of the area under the receiver operating characteristic curve for 1-year event-free survival , the censored c-index for event-free survival , and comparison of event-free survival curves for prognostic-score risk strata . Outcome events were defined as urgent transplant or death without transplant . The noninvasive model performed well in both sample s , and increased performance was not attained by the addition of catheterization-derived variables . Prognostic-score risk groups derived from the noninvasive model in the derivation sample effectively stratified the risk of an outcome event in both sample s ( 1-year event-free survival for derivation and validation sample s , respectively : low risk , 93 % and 88 % ; medium risk , 72 % and 60 % ; high risk , 43 % and 35 % ) . CONCLUSIONS Selection of c and i date s for cardiac transplantation may be improved by use of this noninvasive risk-stratification model PURPOSE The purpose of this study was to use an accelerometer to measure daily walking performance in patients with chronic heart failure ( CHF ) to investigate if this parameter is a determinant of New York Heart Association class and indicative of maximal and functional exercise capacity . METHODS Fifty patients with CHF were instructed to wear an accelerometer for 7 consecutive days while going about their daily business . Maximal and functional exercise capacity was assessed by cardiopulmonary ( VO(2peak ) ) and 6-minute walk testing , respectively . RESULTS Patients in New York Heart Association I , II , and III reached an average total walking time ( TWT ) of 160.6 + /- 35.8 minutes , 133.9 + /- 59.0 minutes , and 76.1 + /- 22.5 minutes per day of which 19 % , 19 % , and 9 % where spent in the fast walking mode ( > 83 m/minute ) , respectively . The TWT correlated strongly with VO(2peak ) ( r = 0.72 ; P < .001 ) and 6-minute walk testing distance ( r = 0.68 ; P < .001 ) . The TWT and time spent in fast walking mode were the strongest determinants in discriminating moderate CHF . CONCLUSION Daily walking performance is a clear determinant of maximal and functional exercise capacities in patients with CHF . Walking intensity in particular is an independent predictor in discriminating patients with advanced heart failure . Monitoring of daily walking performance might aid in detecting disease progression and improve clinical outcome Background Physical activity has not been objective ly measured in prospect i ve cohorts with sufficiently large numbers to reliably detect associations with multiple health outcomes . Technological advances now make this possible . We describe the methods used to collect and analyse accelerometer measured physical activity in over 100,000 participants of the UK Biobank study , and report variation by age , sex , day , time of day , and season . Methods Participants were approached by email to wear a wrist-worn accelerometer for seven days that was posted to them . Physical activity information was extracted from 100Hz raw triaxial acceleration data after calibration , removal of gravity and sensor noise , and identification of wear / non-wear episodes . We report age- and sex-specific wear-time compliance and accelerometer measured physical activity , overall and by hour-of-day , week-weekend day and season . Results 103,712 data sets were received ( 44.8 % response ) , with a median wear-time of 6.9 days ( IQR:6.5–7.0 ) . 96,600 participants ( 93.3 % ) provided valid data for physical activity analyses . Vector magnitude , a proxy for overall physical activity , was 7.5 % ( 2.35 mg ) lower per decade of age ( Cohen ’s d = 0.9 ) . Women had a higher vector magnitude than men , apart from those aged 45 - 54yrs . There were major differences in vector magnitude by time of day ( d = 0.66 ) . Vector magnitude differences between week and weekend days ( d = 0.12 for men , d = 0.09 for women ) and between seasons ( d = 0.27 for men , d = 0.15 for women ) were small . Conclusions It is feasible to collect and analyse objective physical activity data in large studies . The summary measure of overall physical activity is lower in older participants and age-related differences in activity are most prominent in the afternoon and evening . This work lays the foundation for studies of physical activity and its health consequences . Our summary variables are part of the UK Biobank data set and can be used by research ers as exposures , confounding factors or outcome variables in future analyses Reports of studies relating physical activity to stroke and cancer sub-types indicate inconsistent findings . Some are hampered by low statistical power , owing to a low number of events , and a failure to adjust for potential confounding variables . The purpose of this study was to relate physical activity to 12 mortality endpoints in a prospect i ve cohort study of 11,663 men aged 40–64 years who responded to an enquiry about travel activity during a baseline medical examination conducted between 1967 and 1969 . During 25 years of follow-up there were 4672 deaths . Travel activity was inversely related to mortality attributable to all-causes , coronary heart disease , respiratory disease and lung cancer , whereas the association with stroke was positive . There was evidence for attenuation of some of these associations on adjustment for potentially confounding variables . Our simplistic measure of physical activity may , in part , explain the weak associations seen BACKGROUND Previous research demonstrates that participation in light-intensity physical activity ( LIPA ) and moderate-to-vigorous physical activity ( MVPA ) are favorably associated with health-related quality of life ( HRQOL ) . Emerging work demonstrates that sedentary behavior ( SB ) is detrimentally associated with various cardiometabolic biomarkers , with few studies exploring the association of SB on HRQOL , and no studies examining this among congestive heart failure patients . Therefore , the purpose of this study was to examine the potential independent associations of SB on HRQOL among congestive heart failure patients . METHODS Data from the 2003 - 2006 National Health and Nutrition Examination Survey were used . Physical activity was assessed over 7days during all waking hours using the ActiGraph 7164 accelerometer . HRQOL was assessed using the Centers for Disease Control HRQOL index survey . RESULTS 190 participants self-reported a physician-diagnosis of congestive heart failure . After adjustments , SB behavior ( 1-min/day increase ) was associated with worse HRQOL ( β=0.004 ; 95 % CI : 0.0004 - 0.007 ; P=0.03 ) . When MVPA was added as a covariate to this model , SB remained significantly associated with worse HRQOL ( β=0.003 ; 95 % CI : 0.0001 - 0.007 ; P=0.04 ) . However , when adding LIPA to this model that also included MVPA as a covariate , SB was no longer associated with HRQOL ( β=0.0001 ; 95 % CI : -0.003 - 0.004 ; P=0.92 ) . CONCLUSIONS If confirmed by prospect ive/experimental work , this suggests that SB may not have detrimental HRQOL effects among congestive heart failure patients Background Given high rates of obesity , hypertension , and diabetes mellitus , black persons are at risk to develop heart failure . The association of moderate to vigorous physical activity ( MVPA ) and heart failure in black adults is under research ed . The purpose of this study was to explore whether greater MVPA was associated with lower risk of heart failure hospitalizations ( HFHs ) among black adults with normal ejection fractions . Methods and Results We performed a prospect i ve analysis of 4066 black adults who participated in the Jackson Heart Study and who had physical activity measured , had normal ejection fraction on 2‐dimensional echocardiograms , and were followed for 7 years for incident HFH . We used Cox proportional regression analyses adjusted for age , sex , body mass index , smoking status , hypertension , diabetes mellitus , chronic obstructive pulmonary disease , coronary heart disease , atrial fibrillation , and chronic kidney disease and examined effect modification by sex and body mass index . Of the eligible population , 1925 participants , according to the duration of MVPA , had poor health ( 0 minutes/week ) , 1332 had intermediate health ( 1–149 minutes/week ) , and 809 had ideal health ( ≥150 minutes/week ) . There were 168 incident HFHs . MVPA for intermediate and ideal health was associated with decreasing risk of incident HFH ( hazard ratio : 0.70 [ 95 % confidence interval , 49–1.00 ] and 0.35 [ 95 % confidence interval , 0.19–0.64 ] , respectively ; P trend=0.003 ) . The full model revealed hazard ratios of 0.74 [ 95 % confidence interval , 0.52–1.07 ] and 0.41 [ 95 % confidence interval , 0.22–0.74 ] , respectively . There was no effect modification between MVPA and body mass index or sex on incident HFH . Conclusions A dose‐response relationship between increasing levels of MVPA and protection from incident HFH was found in black men and women with normal ejection fractions Purpose : Regular physical activity ( PA ) is recommended for patients with heart failure ( HF ) . However , the clinical and social characteristics of older HF patients with low-level PA and the impact of light-intensity PA on 6-mo postdischarge adverse cardiovascular events are still unclear . Methods : Forty-one older patients who had been admitted because of decompensated HF ( American College of Cardiology [ACC]/American Heart Association [ AHA ] HF classification stage C/D : 76 ± 5 y ) were prospect ively enrolled . Light-intensity ( 1.5 - 2.9 metabolic equivalents [ METs ] ) and moderate-intensity ( ≥3 METs ) PAs were determined by triaxial accelerometry for at least 7 d postdischarge . Six-min walk distance and 36-item Short Form question naire ( SF-36 ) score were evaluated at discharge . HF patients were stratified into either the HFPA-high or HFPA-low group according to median daily PA . Twenty-nine older ACC/AHA stage A/B out patients ( HF-risk ) , who were at risk for HF but no symptoms of HF had developed , also completed these assessment s. Clinical predictors for 6-mo postdischarge HF rehospitalization were assessed . Results : HF patients were anemic and less active . HFPA-low patients were less likely to engage in household work , took fewer steps , and had less light and moderate-intensity PA than HFPA-high patients . There were no differences in 6-min walk distance , SF-36 score , or left ventricular ejection fraction between HFPA-low and HFPA-high patients . Postdischarge PA , especially light-intensity PA , was independently associated with HF rehospitalization . Conclusion : Low volume of PA postdischarge , especially at 1.5 to 2.9 METs , predicts 6-mo postdischarge HF rehospitalization in older HF patients CONTEXT The lifetime risk of heart failure at age 40 years is approximately 1 in 5 in the general population ; however , little is known about the association between modifiable lifestyle factors and the remaining lifetime risk of heart failure . OBJECTIVE To examine the association between modifiable lifestyle factors and the lifetime risk of heart failure in a large cohort of men . DESIGN , SETTING , AND PARTICIPANTS Prospect i ve cohort study using data from 20,900 men ( mean age at baseline , 53.6 years ) from the Physicians ' Health Study I ( 1982 - 2008 ) who were apparently healthy at baseline . Six modifiable lifestyle factors were assessed : body weight , smoking , exercise , alcohol intake , consumption of breakfast cereals , and consumption of fruits and vegetables . MAIN OUTCOME MEASURE Lifetime risk of heart failure . RESULTS During a mean follow-up of 22.4 years , 1200 men developed heart failure . Overall , the lifetime risk of heart failure was 13.8 % ( 95 % confidence interval [ CI ] , 12.9%-14.7 % ) at age 40 years . Lifetime risk remained constant in men who survived free of heart failure through age 70 years and reached 10.6 % ( 95 % CI , 9.4%-11.7 % ) at age 80 years . Lifetime risk of heart failure was higher in men with hypertension than in those without hypertension . Healthy lifestyle habits ( normal body weight , not smoking , regular exercise , moderate alcohol intake , consumption of breakfast cereals , and consumption of fruits and vegetables ) were individually and jointly associated with a lower lifetime risk of heart failure , with the highest risk in men adhering to none of the 6 lifestyle factors ( 21.2 % ; 95 % CI , 16.8%-25.6 % ) and the lowest risk in men adhering to 4 or more desirable factors ( 10.1 % ; 95 % CI , 7.9%-12.3 % ) . CONCLUSION In this cohort of apparently healthy men , adherence to healthy lifestyle factors is associated with a lower lifetime risk of heart failure Aims Exercise is known to be beneficial for patients with heart failure ( HF ) , and these patients should therefore be routinely advised to exercise and to be or to become physically active . Despite the beneficial effects of exercise such as improved functional capacity and favourable clinical outcomes , the level of daily physical activity in most patients with HF is low . Exergaming may be a promising new approach to increase the physical activity of patients with HF at home . The aim of this study is to determine the effectiveness of the structured introduction and access to a Wii game computer in patients with HF to improve exercise capacity and level of daily physical activity , to decrease healthcare re source use , and to improve self‐care and health‐related quality of life . Methods and results A multicentre r and omized controlled study with two treatment groups will include 600 patients with HF . In each centre , patients will be r and omized to either motivational support only ( control ) or structured access to a Wii game computer ( Wii ) . Patients in the control group will receive advice on physical activity and will be contacted by four telephone calls . Patients in the Wii group also will receive advice on physical activity along with a Wii game computer , with instructions and training . The primary endpoint will be exercise capacity at 3 months as measured by the 6 min walk test . Secondary endpoints include exercise capacity at 6 and 12 months , level of daily physical activity , muscle function , health‐related quality of life , and hospitalization or death during the 12 months follow‐up . Conclusion The HF‐Wii study is a r and omized study that will evaluate the effect of exergaming in patients with HF . The findings can be useful to healthcare professionals and improve our underst and ing of the potential role of exergaming in the treatment and management of patients with HF . Trial registration Aims Patients with heart failure often display a distinct pattern of walking characterized by short step-length and frequent short pauses . In the current study we sought to explore if qualitative aspects of movement have any additive value to established factors to predict all-cause mortality in patients with advanced heart failure . Methods and results 60 patients with advanced heart failure ( NYHA III , peak VO2 < 20 ml/kg and LVEF < 35 % ) underwent symptom-limited CPX , echocardiography and routine chemistry . Physical activity was assessed using an accelerometer worn attached to the waist during waking hours for 7 consecutive days . The heart-failure survival score ( HFSS ) was calculated for each patient . All accelerometer-derived variables were analyzed with regard to all-cause mortality and added to a baseline model utilizing HFSS scores . HFSS score was significantly associated with the incidence of death ( P<0.001 ; c-index 0.71 ; CI , 0.67–0.73 ) . The addition of peak skewness to the HFSS model significantly improved the predictive ability with an increase in c-index to 0.74 ( CI , 0.69–0.78 ) , likelihood ratio P<0.02 , establishing skewness as a predictor of increased event rates when accounting for baseline risk . Conclusion The feature skewness , a measure of asymmetry in the intensity level of periods of high physical activity , was identified to be predictive of all-cause mortality independent of the established prognostic model – HFSS and peak VO2 . The findings from the present study emphasize the use of accelerometer analysis in clinical practice to make more accurate prognoses in addition to extract features of physical activity relevant to functional classification OBJECTIVES To compare the correlation between the maximum 6 minutes of daily activity ( M6min ) and st and ard measures of functional capacity in older adults with heart failure ( HF ) with that in younger subjects and its prognostic utility . DESIGN Prospect i ve , cohort study . SETTING Tertiary care , academic HF center . PARTICIPANTS Sixty , ambulatory , adults , New York Heart Association ( NYHA ) Class I to III , stratified into young ( 50.9 + /- 9.4 ) and older cohorts ( 76.8 + /- 8.0 ) . MEASUREMENTS Correlation between M6min and measures of functional capacity ( 6-minute walk test ; 6MWT ) and peak oxygen consumption ( VO(2 ) ) according to cardiopulmonary exercise testing in a subset of subjects . Survival analysis was employed to evaluate the association between M6min and adverse events . RESULTS Adherence to actigraphy was high ( 90 % ) and did not differ according to age . The correlation between M6min and 6MWT was higher in subjects aged 65 and older than in those younger than 65 ( correlation coefficient ( r=0.702 , P<.001 vs r=0.490 , P=.002 ) . M6min was also significantly associated with peak VO(2 ) ( r=0.612 , P=.006 ) . During the study , 26 events occurred ( 2 deaths , 10 hospitalizations , 8 emergency department visits , and 6 intercurrent illnesses ) . The M6min was significantly associated with subsequent events ( hazard ratio=2.728 , 95 % confidence interval=1.10 - 6.77 , P=.03 ) , independent of age , sex , ejection fraction , NYHA class , brain natriuretic peptide , and 6MWT . CONCLUSION The high adherence to actigraphy and association with st and ard measures of functional capacity and independent association with subsequent morbid events suggest that it may be useful for monitoring older adults with HF BACKGROUND AND PURPOSE Cardiac rehabilitation has been shown to be effective in people with chronic heart failure ( CHF ) , particularly in terms of exercise capacity . However , no effects have been found on the level of movement-related everyday activity . Therefore , rehabilitation programs also should focus on enhancing the level of movement-related everyday activity . The aim of this study was to explore factors associated with the level of movement-related everyday activity and with quality of life in people with CHF . SUBJECTS AND METHODS Measurements of movement-related everyday activity ( using an accelerometry-based Activity Monitor ) , quality of life , and associated factors were performed in 36 people with stable CHF ( New York Heart Association classes II and III ) . RESULTS Knee flexion and extension torque , and particularly extension torque , were significantly associated with movement-related everyday activity ( r = .43-.49 , P < .05 ) , whereas nonphysiological factors such as feelings of being disabled were associated with quality of life ( r = .37-.77 , P < or = .01 , P < .05 ) . No relationship was found between movement-related everyday activity and quality of life ( r = .20-.22 , P > .05 ) . DISCUSSION AND CONCLUSION The results indicate that knee torque is associated with the level of movement-related everyday activity in people with CHF and that quality of life is mediated by nonphysiological factors BACKGROUND Reduced physical activity ( PA ) may be one factor that contributes to cognitive decline and dementia in heart failure ( HF ) . Yet , the longitudinal relationship between PA and cognition in HF is poorly understood owing to limitations of past work , including single-time assessment s of PA . This is the first study to examine changes in objective ly measured PA and cognition over time in HF . METHODS AND RESULTS At baseline and 12 weeks , 57 HF patients completed psychosocial self-report measures and a neuropsychological battery and wore an accelerometer for 7 days . At baseline , HF patients spent an average of 597.83 ( SD 75.91 ) minutes per day sedentary . Steps per day declined from baseline to the 12-week follow-up ; there was also a trend for declines in moderate-vigorous PA . Regression analyses controlling for sex , HF severity , and depressive symptoms showed that decreases in light ( P = .08 ) and moderate-vigorous ( P = .04 ) daily PA emerged as strong predictors of declines in attention/executive function over the 12-week period , but not of memory or language . CONCLUSIONS Reductions in daily PA predicted acute decline in attention/executive function in HF , but not of memory or language . Modifications to daily PA may attenuate cognitive decline , and prospect i ve studies are needed to test this possibility PURPOSE We established accelerometer count ranges for the Computer Science and Applications , Inc. ( CSA ) activity monitor corresponding to commonly employed MET categories . METHODS Data were obtained from 50 adults ( 25 males , 25 females ) during treadmill exercise at three different speeds ( 4.8 , 6.4 , and 9.7 km x h(-1 ) ) . RESULTS Activity counts and steady-state oxygen consumption were highly correlated ( r = 0.88 ) , and count ranges corresponding to light , moderate , hard , and very hard intensity levels were < or = 1951 , 1952 - 5724 , 5725 - 9498 , > or = 9499 cnts x min(-1 ) , respectively . A model to predict energy expenditure from activity counts and body mass was developed using data from a r and om sample of 35 subjects ( r2 = 0.82 , SEE = 1.40 kcal x min(-1 ) ) . Cross validation with data from the remaining 15 subjects revealed no significant differences between actual and predicted energy expenditure at any treadmill speed ( SEE = 0.50 - 1.40 kcal x min(-1 ) ) . CONCLUSIONS These data provide a template on which patterns of activity can be classified into intensity levels using the CSA accelerometer The purpose of this study was to determine both an association between mortality and physical activity ( PA ) objective ly measured by accelerometer and cutoff values for PA in Japanese out patients with heart failure ( HF ) . This prospect i ve observational study comprised 170 HF out patients ( mean age , 65.2 years ; 77 % men ) . Peak oxygen uptake ( VO2 ) and the relation between ventilation and carbon dioxide production ( VE/VCO2 slope ) as indices of exercise capacity were measured during cardiopulmonary exercise testing with a cycle ergometer . PA was assessed by accelerometer-measured average step count ( steps ) per day for 1 week . Study endpoint was cardiovascular-related death . Over an average follow-up of 1,377.1 ( median , 1,335 ) days , 31 cardiovascular-related deaths occurred . Patients were then divided into survivor ( n = 139 ) and nonsurvivor ( n = 31 ) groups . Brain natriuretic peptide level was significantly different between groups . Peak VO2 and steps were also significantly lower and VE/VCO2 slope higher in the nonsurvivors versus survivors . Univariate Cox proportional hazards analysis showed brain natriuretic peptide , peak VO2 , VE/VCO2 slope , and steps to be significant prognostic indicators of survival . Multivariate analysis showed PA of ≤4,889.4 steps/day to be a strong and independent predictor of prognosis ( hazard ratio : 2.28 , 95 % confidence interval : 1.31 - 6.30 ; p = 0.008 ) . Kaplan-Meier curves after log-rank test showed significant prognostic difference between PA of ≤4,889.4 and > 4,889.4 steps/day in the 2 groups ( log-rank : 12.19 ; p = 0.0005 ) . In conclusion , step count as objective ly measured by accelerometer may be a prognostic indicator of mortality in Japanese out patients with HF BACKGROUND : Patients hospitalized with decompensated heart failure are at high risk for readmission within 30 days of discharge . Since physical inactivity is associated with increased health care utilization in other diseases , it may predict rehospitalization in heart failure . METHODS : In a single-center , prospect i ve study , physical activity was measured following hospital discharge using an accelerometer on the wrist . We then related this activity to the 30-day all-cause rehospitalization rate in heart failure . Each minute of activity was dichotomized into higher or lower intensity , based on a threshold of 3000 vector magnitude units . Counts above this threshold corresponded to a higher level of physical activity . Logistic regression and Kaplan-Meier survival analyses were used to relate the activity group to 30-day readmissions . RESULTS : Ninety-five patients admitted to a heart failure unit were screened ; 61 met inclusion criteria and provided consent . Fifty patients were evaluated . Forty-six percent were male , mean age was 71 ± 15 years , and 46 % had left ventricular ejection fraction < 40 % . Thirty-day all-cause hospitalizations occurred in 13 of these 50 patients ( 26 % ) . Sixty-six percent and 34 % were dichotomized into the higher and lower physical activity groups , respectively , over the first week ; the latter were more likely to be readmitted within 30 days , with an OR = 5.0 ( 95 % CI , 1.3 - 19.1 ) , P = .02 . CONCLUSION : Physical inactivity is related to 30-day all-cause readmissions for heart failure . Further studies are necessary to assess causality and to determine whether treatments directed at increasing physical activity could reduce readmission rate |
13,839 | 30,513,312 | HighlightsAPOE is not associated with affective symptoms in cognitively impaired subjects .
Studies assessing the affect‐APOE relationship show large heterogeneity in design .Contrasting prior findings could not be explained by this variation in study design .
No association was found between the individual symptoms and APOE & egr;4 carriership or zygosity .
For depression and anxiety , only pooled unadjusted estimates showed positive associations with between‐ study heterogeneity , which could be explained by variation in study design , setting and way of symptom assessment .
Conclusions : There is no evidence that APOE & egr;4 carriership or zygosity is associated with the presence of depression , anxiety , apathy , agitation , irritability or sleep disturbances in cognitively impaired subjects . | Objective : APOE status has been associated to affective symptoms in cognitively impaired subjects , with conflicting results . | BACKGROUND While the relationship of apolipoprotein E ( APOE ) to behavioral symptoms of dementia ( BSD ) has been studied in community-dwelling persons with AD , it has received limited attention within the nursing home ( NH ) population . The aim of this study was to examine the association between APOE genotype and BSD in NH residents using direct observation . METHODS Thirty-six participants , aged 71 - 102 years , were compared using a non-r and omized two-group design with continuous measures . APOE genotype was obtained by buccal swab . BSD , including restlessness , escape restraint , tapping and banging , search ing and w and ering , pacing and walking , and vocalization , were measured using the Modified Agitated Behavior Rating Scale . Participants were observed every 20 minutes for 12 hours per day for five days . Each participant 's mean behavior scores were compared according to the presence or absence of the APOE epsilon4 allele . RESULTS Resident characteristics included a mean MMSE of 10.44 indicating moderate to severe dementia and a mean of 3.44 medical co-morbidities . Fifty-six percent of the participants had one epsilon4 allele . A significant difference was found between APOE epsilon4+/4- and mean behavioral scores ( F(1,31 ) ) = 4.40 , p = 0.04 ) . Restlessness was significantly inversely correlated with MMSE ( r = -0.367 , p = 0.03 ) , but not APOE genotype . There was no significant correlation between proxy reporting and direct observation ( r = 0.257 , p = 0.13 ) . CONCLUSION Findings indicate that the presence of the APOE epsilon4 + genotype increases the risk for BSD in NH residents with dementia . Direct observation proved a more accurate estimate of BSD than proxy report Purpose To identify correlates of self-rated and caregiver-rated quality of life ( QOL ) in community-residing persons with dementia ( PWD ) for intervention development . Methods Cross-sectional data of 254 PWD and their caregivers participating in a clinical trial were derived from in-home assessment s. Self-rated QOL was measured with the Quality of Life-Alzheimer Disease ( QOL-AD ) scale , and caregiver-rated QOL was measured using the QOL-AD and Alzheimer Disease-Related Quality of Life ( ADRQL ) scales . Multivariate modeling identified correlates of the PWD ’ QOL . Results Self-rated QOL was related significantly to participant race , unmet needs , depression , and total medications . Caregiver-rated QOL-AD scores were significantly associated with participant function , unmet needs , depression , and health problems and with caregiver burden and self-rated health . Significant correlates of ADRQL scores included neuropsychiatric symptom severity , functional and cognitive impairment , and caregiver burden and depression . Conclusions Correlates of QOL in community-residing PWD depend on who rates the PWD ’s QOL and which measure is used . Addressing health problems , medication use , and dementia-related unmet needs , reducing functional dependency , and treating neuropsychiatric symptoms in PWD , while reducing caregiver burden and depression , may maximize QOL in those with dementia Background Psychiatric symptoms occur frequently in the course of AD , are a frequent contributor to institutionalization , predict cognitive decline and death , and often require treatment with psychotropic medications . Previous studies investigating the association between APOE genotype and psychiatric symptomatology in AD have reported contradictory results . Objective To determine whether APOE genotype predicts incident psychiatric symptomatology in patients with AD . Methods Eighty-seven patients with AD at early stages and no psychiatric history were followed semiannually for up to 9.3 years ( mean 5.5 years ) for development of delusions , illusions , hallucinations , behavioral symptoms , and depression . Cox proportional hazards models were used to examine the relative risk for incident psychiatric symptomatology ( outcome ) in relation to APOE genotype ( predictor ) . Results The presence of one & egr;4 allele carried a 2.5-fold risk , whereas the presence of two & egr;4 alleles carried a 5.6-fold risk for development of delusions . The associations remained significant even when age , ethnicity , sex , education , duration of disease , and cognitive and functional performance were controlled for . The presence of two & egr;4 alleles was associated with reduced risk for developing hallucinations in the adjusted analysis only . No significant associations were detected between APOE genotype and the incidence of illusions , behavioral symptoms , or depression . Conclusion The presence of one or more & egr;4 alleles is a significant predictor for the incidence of delusions in the course of AD Objective : The authors aim ed to use baseline data of an ongoing large , prospect i ve study in subjects with mild cognitive impairment ( MCI ) to investigate the impact of APOE genotype on the symptom profile of the condition . Methods : Cognitive assessment s included the AD Assessment Scale cognitive subscale ( ADAS-cog ) , the Mini-Mental State Examination ( MMSE ) , and a cognitive battery for assessment of memory , attention , and executive function . Behavioral assessment s included the Neuropsychiatric Inventory and Beck Depression Inventory . Activities of daily living were assessed by the AD Cooperative Study Activities of Daily Living ( ADCS-ADL ) scale . Hippocampal volumes were measured with MRI . Results : A total of 494 of 1,018 study subjects provided APOE data . Approximately 40 % of the subjects were APOE ε4 carriers . APOE ε4 carriers had lower MMSE ( p = 0.01 ) and higher ADAS-cog ( p < 0.0001 ) scores than noncarriers , indicating worse cognitive impairment . APOE ε4 carriers also had greater deficits on New York University delayed paragraph recall and Buschke free and cued selective reminding tests , and on the ADCS-ADL scale ( p < 0.001 ) . They also had smaller hippocampal volumes ( p = 0.002 ) . Behavioral scores were similar across the subgroups . Conclusion : MCI subjects carrying the APOE ε4 allele showed distinct cognitive and imaging profiles , which appeared to resemble those of early Alzheimer patients . APOE ε4 genotype was associated with greater impairments in memory and functional activities as well as hippocampal atrophy OBJECTIVE The authors conducted a prospect i ve cohort study to estimate the risk of incident mild cognitive impairment in cognitively normal elderly ( aged ≥70 years ) individuals with or without neuropsychiatric symptoms at baseline . The research was conducted in the setting of the population -based Mayo Clinic Study of Aging . METHOD A classification of normal cognitive aging , mild cognitive impairment , and dementia was adjudicated by an expert consensus panel based on published criteria . Hazard ratios and 95 % confidence intervals were computed using Cox proportional hazards model , with age as a time scale . Baseline Neuropsychiatric Inventory Question naire data were available for 1,587 cognitively normal persons who underwent at least one follow-up visit . RESULTS The cohort was followed to incident mild cognitive impairment ( N=365 ) or censoring variables ( N=179 ) for a median of 5 years . Agitation ( hazard ratio=3.06 , 95 % CI=1.89 - 4.93 ) , apathy ( hazard ratio=2.26 , 95 % CI=1.49 - 3.41 ) , anxiety ( hazard ratio=1.87 , 95 % CI=1.28 - 2.73 ) , irritability ( hazard ratio=1.84 , 95 % CI=1.31 - 2.58 ) , and depression ( hazard ratio=1.63 , 95 % CI=1.23 - 2.16 ) , observed initially , increased risk for later mild cognitive impairment . Delusion and hallucination did not . A secondary analysis , limited in significance by the small number of study participants , showed that euphoria , disinhibition , and nighttime behaviors were significant predictors of nonamnestic mild cognitive impairment but not amnestic mild cognitive impairment . By contrast , depression predicted amnestic mild cognitive impairment ( hazard ratio=1.74 , 95 % CI=1.22 - 2.47 ) but not nonamnestic mild cognitive impairment . CONCLUSIONS An increased incidence of mild cognitive impairment was observed in community-dwelling elderly adults who had nonpsychotic psychiatric symptoms at baseline . These baseline psychiatric symptoms were of similar or greater magnitude as biomarkers ( genetic and structural MRI ) in increasing the risk of incident mild cognitive impairment Objective : To investigate the population -based interaction between a biological variable ( APOE & egr;4 ) , neuropsychiatric symptoms , and the risk of incident dementia among subjects with prevalent mild cognitive impairment ( MCI ) . Methods : We prospect ively followed 332 participants with prevalent MCI ( aged 70 years and older ) enrolled in the Mayo Clinic Study of Aging for a median of 3 years . The diagnoses of MCI and dementia were made by an expert consensus panel based on published criteria , after review ing neurologic , cognitive , and other pertinent data . Neuropsychiatric symptoms were determined at baseline using the Neuropsychiatric Inventory Question naire . We used Cox proportional hazards models , with age as a time scale , to calculate hazard ratios ( HRs ) and 95 % confidence intervals ( CIs ) . Models were adjusted for sex , education , and medical comorbidity . Results : Baseline agitation , nighttime behaviors , depression , and apathy significantly increased the risk of incident dementia . We observed additive interactions between APOE & egr;4 and depression ( joint effect HR = 2.21 ; 95 % CI = 1.24–3.91 ; test for additive interaction , p < 0.001 ) ; and between APOE & egr;4 and apathy ( joint effect HR = 1.93 ; 95 % CI = 0.93–3.98 ; test for additive interaction , p = 0.031 ) . Anxiety , irritability , and appetite/eating were not associated with increased risk of incident dementia . Conclusions : Among prevalent MCI cases , baseline agitation , nighttime behaviors , depression , and apathy elevated the risk of incident dementia . There was a synergistic interaction between depression or apathy and APOE & egr;4 in further elevating the risk of incident dementia The apolipoprotein E ( APOE ) locus on chromosome 19 has been shown to modify risk , and age at onset , of Alzheimer 's disease ( AD ) . The authors hypothesized that the phenotypic expression of different psychiatric symptoms in patients with AD would be associated with variability in APOE locus . Neuropsychiatric and genetic testing of 120 probable AD patients revealed 28 % had major depression , 17 % had minor depression , 30 % had delusions , and 14 % had hallucinations ; 69 % were carriers of at least one APOE E4 allele ( 14 % homozygous E4/E4 , 49 % heterozygous E3/E4 , 6 % heterozygous E2/E4 , 29 % homozygous E3/E3 , 2 % heterozygous E2/E3 ) . Prevalence of the various psychiatric disturbances did not differ significantly in AD patients with different APOE genotypes . Apolipoprotein E does not appear to modify the risk of developing AD-associated psychiatric symptomatology The etiology of behavioral and psychological symptoms of dementia ( BPSD ) is complex , including putative biological , psychological , social and environmental factors . Recent years have witnessed accumulation of data on the association between genetic factors and behavioral abnormalities in Alzheimer disease ( AD ) . In this research paper , our aim is to evaluate the association between the APOE , CYP46 , PRNP and PRND genes and the profile of neuropsychiatric symptoms in Polish subjects with AD and mild cognitive impairment ( MCI ) . We studied 99 patients with AD and 48 subjects with MCI . The presence and profile of BPSD were evaluated at baseline and prospect ively with the Neuropsychiatric Inventory ( NPI ) . Patients were dichotomized into those having ever experienced a particular symptom and those who did not over the whole disease period . Genotyping was performed using previously described st and ard protocol s. The prevalence of comorbid behavioral symptoms and the overall level of behavioral burden were significantly greater in AD compared with the MCI group . In AD patients , carrier status of the T allele of the 3′UTR ( untranslated region ) PRND polymorphism was associated with an increased cumulative behavioral load and an elevated risk for delusions , anxiety , agitation/aggression , apathy and irritability/emotional ability . Among MCI subjects , APOE ε4 carriers demonstrated a reduced risk for nighttime behavior change . No other statistically significant genotype-phenotype correlations were observed , including the APOE , CYP46 and PRNP genes . A precise estimation of the exact significance of particular polymorphisms in BPSD etiology requires future studies on large population CONTEXT Little is known about the population -based prevalence of neuropsychiatric symptoms in mild cognitive impairment ( MCI ) . OBJECTIVE To estimate the prevalence of neuropsychiatric symptoms in MCI and normal cognitive aging in a defined population . DESIGN Cross-sectional study derived from an ongoing population -based prospect i ve cohort study . SETTING The Mayo Clinic Study of Aging . PARTICIPANTS We studied a r and om sample of 1969 individuals without dementia from the target population of 9965 elderly persons residing in Olmsted County ( Minnesota ) on the prevalence date ( October 1 , 2004 ) . Neuropsychiatric data were available for 319 of 329 subjects with MCI ( 97.0 % ) and 1590 of 1640 subjects with normal cognition ( 97.0 % ) . Neurologic , cognitive , and neuropsychiatric data were obtained from the study participants . A classification of MCI , dementia , and normal cognitive aging was adjudicated by an expert consensus panel . Accordingly , 329 subjects were classified as having MCI and the remaining 1640 subjects were classified as having normal cognition . MAIN OUTCOME MEASURE Neuropsychiatric Inventory Question naire score . RESULTS Multivariate logistic regression analyses were conducted after adjusting for age , sex , and educational status . By considering both the odds ratio ( OR ) and the frequency of a symptom , the most distinguishing features between the 2 groups were apathy ( OR , 4.53 ; 95 % confidence interval [ CI ] , 3.11 - 6.60 ; P < .001 ) , agitation ( 3.60 ; 2.18 - 5.92 ; P < .001 ) , anxiety ( 3.00 ; 2.01 - 4.48 ; P < .001 ) , irritability 2.99 ; 2.11 - 4.22 ; P < .001 ) , and depression ( 2.78 ; 2.06 - 3.76 ; P < .001 ) . The OR was highest for delusion ( 8.12 ; 95 % CI , 2.92 - 22.60 ; P < .001 ) ; however , it was rare in both subjects with MCI ( 11 of 319 [ 3.4 % ] ) and those with normal cognition ( 6 of 1590 [ 0.4 % ] ) . Thus , the population attributable risk for delusion was only 2.62 % compared with 14.60 % for apathy . CONCLUSIONS Nonpsychotic symptoms affected approximately 50 % of subjects with MCI and 25 % of subjects with normal cognition . In contrast , psychotic symptoms were rare OBJECTIVE To estimate the contribution of behavioral and psychological symptoms of dementia ( BPSD ) to the costs of care . METHOD A one-year prospect i ve study of re source utilization recorded monthly by 500 caregivers of community dwelling patients with dementia . The effect of behavior on total , direct and indirect costs of care was examined . RESULTS The total cost of care was $ 1,298 per month and there was a significant independent relationship between costs and BPSD . The incremental cost of a one point increase in Neuropsychiatric Inventory score was $ 30 per month ( 95 % CI : $ 19-$41 ) . CONCLUSION BPSD contribute significantly to the overall costs of dementia care . Interventions targeted at BPSD may help to reduce the staggering societal costs of this illness BACKGROUND The apolipoprotein E ( ApoE ) epsilon 4 and epsilon 2 alleles may influence the age of onset of depressive illness . Depressive illness of late onset is also a risk factor for Alzheimer 's disease ( AD ) , and there is some evidence that the ApoE epsilon 2 allele is associated with depressive symptomatology in AD . Depressive symptomatology in AD may thus share common genetic risk factors with late-onset depressive illness . METHODS The frequency of the epsilon 2 and epsilon 4 alleles of ApoE and their effects on age of onset of disease in three independent groups of subjects , with depressive illness , with AD , and controls , were compared in a defined population from Southeast London . RESULTS The frequency of the ApoE epsilon 2 allele was significantly lower in the depressive illness group compared with the control group and was associated with a later mean age at onset . Subjects with depressive symptomatology in AD had a higher frequency of the ApoE epsilon 2 allele and had a significantly later age of onset of depressive illness compared with the nondepressed AD group . CONCLUSIONS The presence of the ApoE epsilon 2 allele in AD is found to be highly associated with depressive symptomatology , and it is proposed that this subgroup represents the presence of delayed depressive illness and that there are common genetic risk factors between AD and depressive illness BACKGROUND Although neuropsychiatric symptoms in dementia are common , there have been few large long-term prospect i ve studies assessing the course of a broad range of neuropsychiatric symptoms in dementia . OBJECTIVES To investigate the course of neuropsychiatric symptoms in patients with dementia , including data about prevalence , incidence and persistence . METHODS One hundred and ninety-nine patients with dementia were assessed every six months for two-years , using the Neuropsychiatric Inventory ( NPI ) to evaluate neuropsychiatric symptoms . RESULTS Nearly all patients ( 95 % ) developed one or more neuropsychiatric symptoms in the two-year study period . Mood disorders were the most common problem . The severity of depression decreased , whereas the severity of apathy and aberrant motor behaviour increased during follow-up . The cumulative incidence was highest for hyperactive behaviours and apathy . Overall behavioral problems were relatively persistent , but most symptoms were intermittent , with apathy and aberrant motor behaviour being persistent for longer consecutive periods . CONCLUSIONS Neuropsychiatric symptoms in dementia are a common and major problem . Different symptoms have their own specific course , most of the time show a intermittent course , but behavioural problems overall are chronically present . The data have implication s for developing treatment strategies |
13,840 | 30,656,813 | The results of this review provide evidence that the MBSR is more effective than wait-list-control group to reduce depression in older adults with clinical ly significant symptoms immediately following the intervention .
However , there is no clear evidence that the intervention reduced the perception of stress and anxiety , or that positive effects are maintained over the longer term . | Mindfulness-based stress reduction ( MBSR ) has been widely used to improve various physical and mental conditions .
Studies show the intervention is particularly effective in alleviating depression , anxiety , and stress in working-aged adults .
No recent systematic review has focused on the use of MBSR in older adults .
This study aims to examine the effects of MBSR intervention on depression , anxiety , and stress symptoms of older adults . | This pilot study investigated the effectiveness of Mindfulness-Based Cognitive Therapy ( MBCT ) , a treatment combining mindfulness meditation and interventions taken from cognitive therapy , in patients suffering from chronic-recurrent depression . Currently symptomatic patients with at least three previous episodes of depression and a history of suicidal ideation were r and omly allocated to receive either MBCT delivered in addition to treatment-as-usual ( TAU ; N = 14 completers ) or TAU alone ( N = 14 completers ) . Depressive symptoms and diagnostic status were assessed before and after treatment phase . Self-reported symptoms of depression decreased from severe to mild levels in the MBCT group while there was no significant change in the TAU group . Similarly , numbers of patients meeting full criteria for depression decreased significantly more in the MBCT group than in the TAU group . Results are consistent with previous uncontrolled studies . Although based on a small sample and , therefore , limited in their generalizability , they provide further preliminary evidence that MBCT can be used to successfully reduce current symptoms in patients suffering from a protracted course of the disorder OBJECTIVE To assess the effectiveness of mindfulness-based stress reduction ( MBSR ) for chronic insomnia and combined depressive or anxiety symptoms of older adults aged 75 years and over . DESIGN A r and omized , controlled , single-blind clinical trial . PATIENTS AND METHODS Participants included 60 adults aged 75 years and over with chronic insomnia . Participants were r and omly assigned to the eight-week MBSR group or the wait-list control group . Assessment s using the Pittsburgh Sleep Quality Index ( PSQI ) , Self-rating Anxiety Sale ( SAS ) , and Geriatric Depression Scale ( GDS ) were taken at baseline and post-treatment . For each outcome measure , a repeated measures analysis of variance was used to detect changes across assessment s. RESULTS There was a significant time × group interaction for the PSQI global score ( P = .006 ) ; the MBSR group had a decrease in the PSQI global score ( Cohen׳s d = 1.12 ) , while the control group did not ( Cohen׳s d = -0.06 ) . Among the PSQI components , there was a significant time × group interaction for daytime dysfunction ( P = .048 ) ; Cohen׳s d of the MBSR group was 0.76 , while Cohen׳s d of control group was -0.04 . There was no significant time × group interaction for the SAS score ( P = .116 ) , while for the GDS there was a significant time × group interaction ( P = .039 ) ; the Cohen׳s d value for the MBSR group was 1.20 , and it was 0.12 for the control group . CONCLUSION This study demonstrated that the MBSR program could be a beneficial treatment for chronic insomnia in adults aged 75 years and older OBJECTIVE To determine whether neurocognitive performance and clinical outcomes can be enhanced by a mindfulness intervention in older adults with stress disorders and cognitive complaints . To explore decreased hypothalamic-pituitary-adrenal ( HPA ) axis activity as a possible mechanism . METHODS 103 adults aged 65 years or older with an anxiety or depressive disorder ( diagnosed according to DSM-IV criteria ) and subjective neurocognitive difficulties were recruited in St. Louis , Missouri , or San Diego , California , from September 2012 through August 2013 and r and omly assigned in groups of 5 - 8 to mindfulness-based stress reduction ( MBSR ) or a health education control condition matched for time , attention , and credibility . The primary outcomes were memory ( assessed by immediate and delayed paragraph and list recall ) and cognitive control ( Delis-Kaplan Executive Function System Verbal Fluency Test and Color Word Interference Test ) . Other outcomes included clinical symptoms ( worry , depression , anxiety , and global improvement ) . HPA axis activity was assessed using peak salivary cortisol . Outcomes were measured immediately post-intervention and ( for clinical outcomes only ) at 3- and 6-month follow up . RESULTS On the basis of intent-to-treat principles using data from all 103 participants , the mindfulness group experienced greater improvement on a memory composite score ( P = .046 ) . Groups did not differ on change in cognitive control . Participants receiving MBSR also improved more on measures of worry ( P = .042 ) and depression ( P = .049 ) at posttreatment and on worry ( P = .02 ) , depression ( P = .002 ) , and anxiety ( P = .002 ) at follow-up and were more likely to be rated as much or very much improved as rated by the Clinical Global Impressions-Improvement scale ( 47 % vs 27 % , χ² = 4.5 , P = .03 ) . Cortisol level decreased to a greater extent in the mindfulness group , but only among those participants with high baseline cortisol . CONCLUSIONS In this population of older adults with stress disorders and neurocognitive difficulties , a mindfulness intervention improves clinical outcomes such as excessive worry and depression and may include some forms of immediate memory performance . TRIAL REGISTRATION Clinical Trials.gov identifier : NCT01693874 OBJECTIVES Patients with chronic obstructive lung disease ( COPD ) suffer from significant dyspnea and may benefit from complementary and alternative medicine ( CAM ) therapies aim ed at mitigating symptoms . The objective of this study was to test the efficacy of a mindfulness-based breathing therapy ( MBBT ) on improving symptoms and health-related quality of life in those with COPD . DESIGN We conducted a r and omized controlled trial of 8-week mindfulness-based breathing therapy ( MBBT ) compared to support groups to test efficacy on improving symptoms and health-related quality of life in those with COPD . SETTING The setting for this study was an academic-affiliated veterans healthcare system . SUBJECTS The subjects consisted of 86 patients with COPD . INTERVENTIONS MBBT included weekly meetings practicing mindfulness mediation and relaxation response . OUTCOME MEASURES The main outcome measure was a post 6-minute-walk test ( 6MWT ) Borg dyspnea assessment . Other outcome measures included health-related quality of life measures , 6MWT distance , symptom scores , exacerbation rates , and measures of stress and mindfulness . Analysis of covariance compared differences in outcomes between groups ; paired t test evaluated changes within groups . RESULTS Participants were predominantly elderly men with moderate to severe COPD . We found no improvements in dyspnea ( post 6MWT Borg difference between the MBBT and support group was 0.3 ( 95 % confidence interval [ CI ] : -1.1 , 1.7 ) . We found no differences between groups in almost all other outcome measures by either intention-to-treat analysis or within the subset that completed assigned group sessions . For the physical summary scale of the generic Short Form-36 for Veterans , the difference between outcomes favored the support group ( 4.3 , 95 % CI : 0.4 , 8.1 ) . Participant retention was low compared to mind-body trials that r and omize from CAM wait lists . CONCLUSIONS This trial found no measurable improvements in patients with COPD receiving a mindfulness-based breathing CAM therapy compared to a support group , suggesting that this intervention is unlikely to be an important therapeutic option for those with moderate-to-severe COPD 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 Objectives : To examine the effects of age and depressive symptom severity on changes in positive affect among older adults r and omly assigned to a Mindfulness-Based Stress Reduction ( MBSR ) program or a Waitlist Control group . Drawing from the Motivational Theory of Life-Span Development , we hypothesized that lower levels of depressive symptom severity and older age would be associated with greater positive affect in response to the MBSR intervention . Methods : Data were collected from a sample of community-dwelling English-speaking adults ( n = 200 ) aged ≥ 65 , r and omly assigned to an eight-week MBSR program or a Waitlist Control group . Our main outcome variable was a five-item measure of positive affect , which was measured at study entry as well as eight weeks and six months later . Results : At the six-month follow-up , we observed group by baseline depressive symptom severity ( β = −.17 , p = .02 ) and group by baseline depressive symptom severity by age ( β = −.14 , p = .05 ) interactions . Among MBSR participants , greater baseline depressive symptom severity was also associated with less improvement in positive affect at the six-month follow-up ( β = −.30 , p = .003 ) . Findings were qualified by a significant depressive symptom severity by age interaction ( β = −.25 , p = .01 ) , such that MBSR participants who were 70 and over with lower baseline depressive symptom severity having the greatest improvement in positive affect at the six-month follow-up . Conclusion : MBSR improves positive affect for older adults with lower depressive symptom severity , perhaps because it capitalizes on naturalistic changes in control strategies The cultivation of mindfulness has received increasing attention over the past 2 decades because of its association with increased psychological well-being and reduced stress-related health disorders . Given the robust positive association between perceived stress and cognitive impairment in late life , the current study evaluated the association between trait mindfulness , psychological well-being , and cognitive function in 73 healthy community-dwelling older adults . Controlling for a priori covariates , multivariate regression analyses showed a significant association between trait mindfulness and measures of psychological well-being , including self-reported depressive symptoms , quality of life , and stress profile . Analyses further showed a significant association between trait mindfulness and executive function , namely set shifting . No association was found for declarative memory . Mediation analyses showed that the association between mindfulness and cognitive function is mediated by perceived stress . This research supports the importance of cultivating mindfulness in late life to ensure cognitive and emotional well-being The purpose of this study was to test the feasibility and effectiveness of an adapted 8-week Mindfulness-Based Stress Reduction ( MBSR ) program for elders in a continuing care community . This mixed- methods study used both quantitative and qualitative measures . A r and omized waitlist control design was used for the quantitative aspect of the study . Thirty-nine elderly were r and omized to MBSR ( n = 20 ) or a waitlist control group ( n = 19 ) , mean age was 82 years . Both groups completed pre – post measures of health-related quality of life , acceptance and psychological flexibility , facets of mindfulness , self-compassion , and psychological distress . A subset of MBSR participants completed qualitative interviews . MBSR participants showed significantly greater improvement in acceptance and psychological flexibility and in role limitations due to physical health . In the qualitative interviews , MBSR participants reported increased awareness , less judgment , and greater self-compassion . Study results demonstrate the feasibility and potential effectiveness of an adapted MBSR program in promoting mind – body health for elders In a r and omized controlled trial , we investigated the effects of karate versus a mindfulness-based stress reduction ( MBSR ) intervention on well-being and cognitive functioning in older adults . Fifty-five adults ( 52–81 years old ) participated in twice-weekly karate versus MBSR sessions or no training for 8 weeks . In pre- and post assessment s , subjective well-being , health , cognitive functioning , and chronic stress were measured . Pre assessment hair cortisol served as physiological stress marker . The results showed an improvement for the karate group , but not the MBSR and control group , in subjective mental health and anxiety as well as cognitive processing speed . The MBSR group showed by trend as a decrease in stress . No significant correlation between pre assessment hair cortisol and post assessment outcomes could be established . But the higher the level of baseline self-reported perceived stress , the higher the increase in depression , anxiety , and chronic stress . Generally , it can be assumed that karate and MBSR showed only small training effects concerning the assessed emotional and cognitive parameters |
13,841 | 31,426,481 | The included studies indicated that plyometric training seems to increase vertical jump performance , strength , horizontal jump performance , flexibility and agility/speed in volleyball players . | Volleyball is considered a very explosive and fast-paced sport in which plyometric training is widely used .
Our purpose was to review the effects of plyometric training on volleyball players ' performance . | PURPOSE This study compared the effects of skill-based and plyometric conditioning ( both performed in addition to regular volleyball training twice a week for 12 wk ) on fitness parameters in female junior volleyball players . METHODS The participants [ n = 47 ; age : 16.6 ( 0.6 ) y ; mass : 59.4 ( 8.1 ) kg ; height : 175.1 ( 3.0 ) cm ] were r and omized into a plyometric ( n = 13 ) , a skill-based ( n = 17 ) , and a control ( n = 17 ) groups . The variables included body height , body mass , calf girth , calf skinfold , corrected calf girth , countermovement jump , 20-m-sprint , medicine ball toss , and sit- and -reach test . RESULTS Two-way analysis of variance ( time × group ) effects for time were significant ( P < .05 ) for all variables except body mass . Significant group × time interactions were observed for calf skinfold [ η2 = .14 ; medium effect size ( ES ) ] , 20-m sprint ( η2 = .09 ; small ES ) , countermovement jump ( η2 = .29 ; large ES ) , medicine ball ( η2 = .58 ; large ES ) , with greater gains ( reduction of skinfold ) for plyometric group , and sit- and -reach ( η2 = .35 ; large ES ) , with greater gains in plyometric and skill-based groups . The magnitude-based inference indicated positive changes in 1 ) medicine ball toss and countermovement jump for all groups ; 2 ) sit- and -reach for the plyometric and skill-based groups ; and 3 ) 20-m sprint , calf girth , calf skinfold , and corrected calf girth for plyometric group only . CONCLUSION Selected variables can be improved by adding 2 plyometric training sessions throughout the period of 12 weeks . Additional skill-based conditioning did not contribute to improvement in the studied variables compared with regular volleyball training OBJECTIVE To compare differences in kinematic and kinetic parameters of knee , hip and ankle joints between male and female college volleyball players . DESIGN Cross-sectional study . BACKGROUND L and ing injuries , which usually involve anterior cruciate ligament injuries , are common in volleyball with a higher incidence in females . L and ing preferences of both male and female players may provide additional background about the mechanisms contributing to the anterior cruciate ligament injuries . METHODS Eight female and eight male college volleyball players performed spike and block l and ings from 40 and 60 cm height platforms . Lower extremity joint kinetics and kinematics , and leg muscle strengths were recorded . RESULTS Females demonstrated significantly lower knee and hip flexion angles compared to their male counterparts in knee flexion at 40 cm spike and hip flexion at 40 cm block l and ings . Group comparison also revealed that male players ' peak knee extensor moment at 60 cm block l and ing was significantly different than female players . Additionally , female players applied significantly higher normalized ground reaction forces and males knee flexion angles and thigh muscle strength results positive and highly correlated but relation could not found in females . It is likely that females may not use their thigh muscles as effective as males in l and ing . CONCLUSION Female volleyball players initiate different lower extremity mechanics during l and ings than that of males . RELEVANCE Identifying the l and ing strategy differences between female and male college volleyball players may provide detailed perspective about the load distribution in lower extremity joints for determining major factors affecting the increased incidence of anterior cruciate ligament injuries in females This study investigated the effects of a plyometric training program and a traditional weight-training program on the onset rate of fatigue in the vertical jump in women . Twenty-five untrained college women ranging in age from 18–35 were r and omly separated into 3 groups : a plyometric group , a traditional weight-training group , and a control ( untrained ) group . For the purpose of this study , the traditional weight-training group was defined as performing 3 sets of 10 repetitions at 70 % of the subject 's 1 repetition maximum ( 1RM ) . Training took place over a 10-week period for both the plyometric and traditional weight-trained groups . The plyometric group prolonged the onset of fatigue by 3.85 seconds as compared with their pretest data . The traditional weight-training group fatigued 0.55 seconds faster after training was implemented as compared with their pretest data . These results showed a significant difference between the groups in their onset rates of fatigue ( p < 0.05 ) . The results of this study show that a plyometric training program prolongs the onset rate of fatigue in the vertical jump in women as compared with a traditional weight-training program OBJECTIVES To compare the impact of short term training with resistance plus plyometric training ( RT+P ) or electromyostimulation plus plyometric training ( EMS+P ) on explosive force production in elite volleyball players . DESIGN Sixteen elite volleyball players of the first German division participated in a training study . METHODS The participants were r and omly assigned to either the RT+P training group ( n=8 ) or the EMS+P training group ( n=8 ) . Both groups participated in a 5-week lower extremity exercise program . Pre and post tests included squat jumps ( SJ ) , countermovement jumps ( CMJ ) , and drop jumps ( DJ ) on a force plate . The three-step reach height ( RH ) was assessed using a custom-made vertec apparatus . Fifteen m straight and lateral sprint ( S15s and S15l ) were assessed using photoelectric cells with interims at 5 m and 10 m. RESULTS RT+P training result ed in significant improvements in SJ ( + 2.3 % ) and RH ( + 0.4 % ) performance . The EMS+P training group showed significant increases in performance of CMJ ( + 3.8 % ) , DJ ( + 6.4 % ) , RH ( + 1.6 % ) , S15l ( -3.8 % ) and after 5 m and 10 m of the S15s ( -2.6 % ; -0.5 % ) . The comparison of training-induced changes between the two intervention groups revealed significant differences for the SJ ( p=0.023 ) in favor of RT+P and for the S15s after 5 m ( p=0.006 ) in favor of EMS+P. CONCLUSIONS The results indicate that RT+P training is effective in promoting jump performances and EMS+P training increases jump , speed and agility performances of elite volleyball players PURPOSE Numerous studies have reported that l and -based plyometrics can improve muscular strength , joint stability , and vertical jump ( VJ ) in athletes ; however , due to the intense nature of plyometric training , the potential for acute muscle soreness or even musculoskeletal injury exists . Performance of aquatic plyometric training ( APT ) could lead to similar benefits , but with reduced risks due to the buoyancy of water . Unfortunately , there is little information regarding the efficacy of APT . Thus , the purpose of this study was to examine the effects of APT on VJ and muscular strength in volleyball players . METHODS Nineteen female volleyball players ( aged 15 + /- 1 yr ) were r and omly assigned to perform 6 wk of APT or flexibility exercises ( CON ) twice weekly , both in addition to traditional preseason volleyball training . Testing of leg strength was performed at baseline and after 6 wk , and VJ was measured at baseline and after 2 , 4 , and 6 wk . RESULTS Similar increases in VJ were observed in both groups after 4 wk ( APT = 3.1 % , CON = 4.9 % ; both P < 0.05 ) ; however , the APT group improved by an additional 8 % ( P < 0.05 ) from week 4 to week 6 , whereas there was no further improvement in the CON group ( -0.9 % ; P = NS ) . After 6 wk , both groups displayed significant improvements in concentric peak torque during knee extension and flexion at 60 and 180 degrees x s(-1 ) ( all P < 0.05 ) . CONCLUSIONS The combination of APT and volleyball training result ed in larger improvements in VJ than in the CON group . Thus , given the likely reduction in muscle soreness with APT versus l and -based plyometrics , APT appears to be a promising training option CONTEXT Plyometric training is credited with providing benefits in performance and dynamic restraint . However , limited prospect i ve data exist quantifying kinematic adaptations such as amortization time , glenohumeral rotation , and scapulothoracic position , which may underlie the efficacy of plyometric training for upper-extremity rehabilitation or performance enhancement . OBJECTIVE To measure upper-extremity kinematics and plyometric phase times before and after an 8-wk upper-extremity strength- and plyometric-training program . DESIGN R and omized pretest-posttest design . SETTING Research laboratory . PARTICIPANTS 40 recreationally active men ( plyometric group , age 20.43 ± 1.40 y , height 180.00 ± 8.80 cm , weight 73.07 ± 7.21 kg ; strength group , age 21.95 ± 3.40 y , height 173.98 ± 11.91 cm , weight 74.79 ± 13.55 kg ) . INTERVENTION Participants were r and omly assigned to either a strength-training group or a strength- and plyometric-training group . Each participant performed the assigned training for 8 wk . MAIN OUTCOME MEASURES Dynamic and static glenohumeral and scapular-rotation measurements were taken before and after the training programs . Dynamic measurement of scapular rotation and time spent in each plyometric phase ( concentric , eccentric , and amortization ) during a ball-toss exercise were recorded while the subjects were fitted with an electromagnetic tracking system . Static measures included scapular upward rotation at 3 different glenohumeral-abduction angles , glenohumeral internal rotation , and glenohumeral external rotation . RESULTS Posttesting showed that both groups significantly decreased the time spent in the amortization , concentric , and eccentric phases of a ball-toss exercise ( P < .01 ) . Both groups also exhibited significantly decreased static external rotation and increased dynamic scapular upward rotation after the training period ( P < .01 ) . The only difference between the training protocol s was that the plyometric-training group exhibited an increase in internal rotation that was not present in the strength-training group ( P < .01 ) . CONCLUSION These findings support the use of both upper-extremity plyometrics and strength training for reducing commonly identified upper-extremity-injury risk factors and improving upper-extremity performance |
13,842 | 28,850,172 | Authors ' conclusions Isoniazid prophylaxis given to all children diagnosed with HIV may reduce the risk of active TB and death in HIV‐positive children not on ART in studies from Africa .
For children on ART , no clear benefit was detected . . | Abstract Background Tuberculosis ( TB ) is an important cause of illness and death in HIV‐positive children living in areas of high TB prevalence .
We know that isoniazid prophylaxis prevents TB in HIV‐negative children following TB exposure , but there is uncertainty related to its role in TB preventive treatment in HIV‐positive children .
Objectives To summarise the effects of TB preventive treatment versus placebo in HIV‐positive children with no known TB contact on active TB , death , and reported adverse events . | Background Tuberculosis ( TB ) is a major cause of morbidity and mortality among children infected with HIV . Strategies to prevent TB in children include isoniazid preventive therapy ( IPT ) and antiretroviral therapy ( ART ) . IPT and ART have been reported to reduce TB incidence in adults but there are few studies in children . Objective To investigate the combined effect of IPT and ART on TB risk in children infected with HIV . Methods A cohort analysis was done within a prospect i ve , double-blinded , placebo-controlled trial of isoniazid ( INH ) compared with placebo in children infected with HIV in Cape Town , South Africa , a high TB incidence setting . In May 2004 the placebo arm was terminated and all children were switched to INH . ART was not widely available at the start of the study , but children were started on ART following the establishment of the national ART program in 2004 . Data were analysed using Cox proportional hazard regression . Results After adjusting for age , nutritional status and immunodeficiency at enrolment , INH alone , ART alone and INH combined with ART reduced the risk of TB disease by 0.22 ( 95 % CI 0.09 to 0.53 ) , 0.32 ( 95 % CI 0.07 to 1.55 ) and 0.11 ( 95 % CI 0.04 to 0.32 ) respectively . INH reduced the risk of TB disease in children on ART by 0.23 ( 95 % CI 0.05 to 1.00 ) . Conclusions The finding that IPT may offer additional protection in children on ART has significant public health implication s because this offers a possible strategy for reducing TB in children infected with HIV . Widespread use of this strategy will however require screening of children for active TB disease . Trial registration Trial registration — Clinical Trials NCT00330304 BACKGROUND The dual epidemic of human immunodeficiency virus ( HIV ) and tuberculosis is a major cause of sickness and death in sub-Saharan Africa . We conducted a double-blind , r and omized , placebo-controlled trial of preexposure isoniazid prophylaxis against tuberculosis in HIV-infected children and uninfected children exposed to HIV during the perinatal period . METHODS We r and omly assigned 548 HIV-infected and 804 HIV-uninfected infants ( 91 to 120 days of age ) to isoniazid ( 10 to 20 mg per kilogram of body weight per day ) or matching placebo for 96 weeks . All patients received bacille Calmette-Guérin ( BCG ) vaccination against tuberculosis within 30 days after birth . HIV-infected children had access to antiretroviral therapy . The primary outcome measures were tuberculosis disease and death in HIV-infected children and latent tuberculosis infection , tuberculosis disease , and death in HIV-uninfected children within 96 to 108 weeks after r and omization . RESULTS Antiretroviral therapy was initiated in 98.9 % of HIV-infected children during the study . Among HIV-infected children , protocol -defined tuberculosis or death occurred in 52 children ( 19.0 % ) in the isoniazid group and 53 ( 19.3 % ) in the placebo group ( P=0.93 ) . Among HIV-uninfected children , there was no significant difference in the combined incidence of tuberculosis infection , tuberculosis disease , or death between the isoniazid group ( 39 children , 10 % ) and the placebo group ( 45 children , 11 % ; P=0.44 ) . The rate of tuberculosis was 121 cases per 1000 child-years ( 95 % confidence interval [ CI ] , 95 to 153 ) among HIV-infected children as compared with 41 per 1000 child-years ( 95 % CI , 31 to 52 ) among HIV-uninfected children . There were no significant differences in clinical or severe laboratory toxic effects between treatment groups . CONCLUSIONS Primary isoniazid prophylaxis did not improve tuberculosis-disease-free survival among HIV-infected children or tuberculosis-infection-free survival among HIV-uninfected children immunized with BCG vaccine . Despite access to antiretroviral therapy , the burden of tuberculosis remained high among HIV-infected children . ( Funded by the National Institutes of Health and Secure the Future ; Clinical Trials.gov number , NCT00080119 . ) Background Tuberculosis contributes significantly to morbidity and mortality among HIV-infected children in sub-Saharan Africa . Isoniazid prophylaxis can reduce tuberculosis incidence in this population . However , for the treatment to be effective , adherence to the medication must be optimized . We investigated adherence to isoniazid prophylaxis administered daily , compared to three times a week , and predictors of adherence amongst HIV-infected children . Methods We investigated adherence to study medication in a two centre , r and omized trial comparing daily to three times a week dosing of isoniazid . The study was conducted at two tertiary paediatric care centres in Cape Town , South Africa . Over a 5 year period , we followed 324 HIV-infected children aged ≥ 8 weeks . Adherence information based on pill counts was available for 276 children . Percentage adherence was calculated by counting the number of pills returned . Adherence ≥ 90 % was considered to be optimal . Analysis was done using summary and repeated measures , comparing adherence to the two dosing schedules . Mean percentage adherence ( per child during follow-up time ) was used to compare the mean of each group as well as the proportion of children achieving an adherence of ≥ 90 % in each group . For repeated measures , percentage adherence ( per child per visit ) was dichotomized at 90 % . A logistic regression model with generalized estimating equations , to account for within-individual correlation , was used to evaluate the impact of the dosing schedule . Adjustments were made for potential confounders and we assessed potential baseline and time-varying adherence determinants . Results The overall adherence to isoniazid was excellent , with a mean adherence of 94.7 % ( 95 % confidence interval [ CI ] 93.5 - 95.9 ) ; similar mean adherence was achieved by the group taking daily medication ( 93.8 % ; 95 % CI 92.1 - 95.6 ) and by the three times a week group ( 95.5 % ; 95 % CI 93.8 - 97.2 ) . Two-hundred and seventeen ( 78.6 % ) children achieved a mean adherence of ≥ 90 % . Adherence was similar for daily and three times a week dosing schedules in univariate ( odds ratio [ OR ] 0.88 ; 95 % CI 0.66 - 1.17 ; P = 0.38 ) and multivariate ( adjusted OR 0.85 ; 95 % CI 0.64 - 1.11 ; P = 0.23 ) models . Children from overcrowded homes were less adherent ( adjusted OR 0.71 ; 95 % CI 0.54 - 0.95 ; P = 0.02 ) . Age at study visit was predictive of adherence , with better adherence achieved in children older than 4 years ( adjusted OR 1.96 ; 95 % CI 1.16 - 3.32 ; P = 0.01 ) . Conclusion Adherence to isoniazid was excellent regardless of the dosing schedule used . Intermittent dosing of isoniazid prophylaxis can be considered as an alternative to daily dosing , without compromising adherence or efficacy . Trial registration Clinical Trials BACKGROUND Antiretroviral therapy reduces the risk of tuberculosis , but tuberculosis is more common in people with HIV than in people without HIV . We aim ed to assess the effect of isoniazid preventive therapy on the risk of tuberculosis in people infected with HIV-1 concurrently receiving antiretroviral therapy . METHODS For this pragmatic r and omised double-blind , placebo-controlled trial in Khayelitsha , South Africa , we r and omly assigned ( 1:1 ) patients to receive either isoniazid preventive therapy or a placebo for 12 months ( could be completed during 15 months ) . R and omisation was done with r and om number generator software . Participants , physicians , and pharmacy staff were masked to group assignment . The primary endpoint was time to development of incident tuberculosis ( definite , probable , or possible ) . We excluded tuberculosis at screening by sputum culture . We did a modified intention-to-treat analysis and excluded all patients r and omly assigned to groups who withdrew before receiving study drug or whose baseline sputum culture results suggested prevalent tuberculosis . This study is registered with Clinical Trials.gov , number NCT00463086 . FINDINGS 1329 participants were r and omly assigned to receive isoniazid preventive therapy ( n=662 ) or placebo ( n=667 ) between Jan 31 , 2008 , and Sept 31 , 2011 , and contributed 3227 person-years of follow-up to the analysis . We recorded 95 incident cases of tuberculosis ; 37 were in the isoniazid preventive therapy group ( 2·3 per 100 person-years , 95 % CI 1·6 - 3·1 ) , and 58 in the placebo group ( 3·6 per 100 person-years , 2·8 - 4·7 ; hazard ratio [ HR ] 0·63 , 95 % CI 0·41 - 0·94 ) . Study drug was discontinued because of grade 3 or 4 raised alanine transaminase concentrations in 19 of 662 individuals in the isoniazid preventive therapy group and ten of the 667 individuals in the placebo group ( risk ratio 1·9 , 95 % CI 0·90 - 4·09 ) . We noted no evidence that the effect of isoniazid preventive therapy was restricted to patients who were positive on tuberculin skin test or interferon gamma release assay ( adjusted HR for patients with negative tests 0·43 [ 0·21 - 0·86 ] and 0·43 [ 0·20 - 0·96 ] ; for positive tests 0·86 [ 0·37 - 2·00 ] and 0·55 [ 0·26 - 1·24 ] , respectively ) . INTERPRETATION Without a more predictive test or a multivariate algorithm that predicts benefit , isoniazid preventive therapy should be recommended to all patients receiving antiretroviral therapy in moderate or high incidence areas irrespective of tuberculin skin test or interferon gamma release assay status . FUNDING Department of Health of South Africa , the Wellcome Trust , Médecins Sans Frontières , European and Developing Countries Clinical Trials Partnership , Foundation for Innovation and New Diagnostics , the European Union , and Hasso Plattner ( Institute of Infectious Diseases and Molecular Medicine , University of Cape Town ) BACKGROUND There are limited population -based estimates of tuberculosis incidence among human immunodeficiency virus (HIV)-infected and HIV-uninfected infants aged < or = 12 months . We aim ed to estimate the population -based incidence of culture-confirmed tuberculosis among HIV-infected and HIV-uninfected infants in the Western Cape Province , South Africa . METHODS The incidences of pulmonary , extrapulmonary , and disseminated tuberculosis were estimated over a 3-year period ( 2004 - 2006 ) with use of prospect i ve representative hospital surveillance data of the annual number of culture-confirmed tuberculosis cases among infants . The total number of HIV-infected and HIV-uninfected infants was calculated using population -based estimates of the total number of live infants and the annual maternal HIV prevalence and vertical HIV transmission rates . RESULTS There were 245 infants with culture-confirmed tuberculosis . The overall incidences of tuberculosis were 1596 cases per 100,000 population among HIV-infected infants ( 95 % confidence interval [ CI ] , 1151 - 2132 cases per 100,000 population ) and 65.9 cases per 100,000 population among HIV-uninfected infants ( 95 % CI , 56 - 75 cases per 100,000 population ) . The relative risk of culture-confirmed tuberculosis among HIV-infected infants was 24.2 ( 95 % CI , 17 - 34 ) . The incidences of disseminated tuberculosis were 240.9 cases per 100,000 population ( 95 % CI , 89 - 433 cases per 100,000 population ) among HIV-infected infants and 14.1 cases per 100,000 population ( 95 % CI , 10 - 18 cases per 100,000 population ) among HIV-uninfected infants ( relative risk , 17.1 ; 95 % CI , 6 - 34 ) . CONCLUSIONS This study indicates the magnitude of the tuberculosis disease burden among HIV-infected infants and provides population -based comparative incidence rates of tuberculosis among HIV-infected infants . This high risk of tuberculosis among HIV-infected infants is of great concern and may be attributable to an increased risk of tuberculosis exposure , increased immune-mediated tuberculosis susceptibility , and /or possible limited protective effect of bacille Calmette-Guérin vaccination . Improved tuberculosis control strategies , including maternal tuberculosis screening , contact tracing of tuberculosis-exposed infants coupled with preventive chemotherapy , and effective vaccine strategies , are needed for infants in setting s where HIV infection and tuberculosis are highly endemic Background . Childhood tuberculosis ( TB ) is difficult to diagnose reliably because signs and symptoms are nonspecific and sputum for direct microscopy is difficult to obtain , especially in very young children . This diagnostic dilemma is thought to have increased with the HIV p and emic . Few studies on treatment outcome of dually infected children in high endemic countries have been reported . This study examines the impact of HIV infection on clinical presentation , diagnostic criteria and treatment outcome of TB in Ethiopian children . Methods . A prospect i ve cohort study of children with TB diagnosed in Addis Ababa from December 1995 to January 1997 in which HIV-positive children were compared with HIV-negative children with regard to medical history , signs and symptoms , nutritional status , chest radiography , tuberculin skin test , response to TB treatment and final outcome . Mycobacterium tuberculosis was cultured in children with pulmonary manifestations . Results . HIV-positive children were younger , were underweight and had a 6-fold higher mortality than HIV-negative children . The tuberculin skin test was less sensitive and chest radiography was less specific in HIV-infected patients . Adherence to treatment was high ( 96 % ) , and the cure rate was 58 % for HIV-positive and 89 % for HIV-negative TB patients . Conclusion . HIV-positive children are at risk of diagnostic error as well as delayed diagnosis of TB . TB manifestations are more severe and progression to death is more rapid than in HIV-negative children . Weight for age may be used to identify children at high risk of a fatal outcome Setting : Rifampicin may reduce plasma efavirenz concentrations by inducing the expression of the cytochrome P450 2B6 , which metabolizes efavirenz . However , there is no data in pediatric patient population s. Methods : We measured plasma efavirenz concentrations in 15 children during and after rifampicin-based antitubercular treatment . They were receiving st and ard doses of efavirenz as part of antiretroviral treatment . Trough concentration ( Cmin ) was estimated by extrapolation of the log-linear concentration-time line to 24 hours after the previous dose . Results : Wide interpatient variation and marked bimodality of efavirenz concentrations were observed . Efavirenz Cmin was not significantly different during vs. after antitubercular treatment ( median 0.83 mg/L interquartile range 0.59 - 6.57 vs. median 0.86 mg/L interquartile range 0.61 - 3.56 ; P = 0.125 ) . Nine ( 60 % ) and 8 ( 53 % ) children had subtherapeutic Cmin ( < 1 mg/L ) during and after antitubercular treatment , respectively . Conclusions : Concomitant rifampicin-based antitubercular treatment was not an important determinant of efavirenz concentrations . The substantial proportion of participants with estimated Cmin < 1 mg/L could result in the rapid emergence of efavirenz-resistant mutations and treatment failure SETTING Tuberculosis ( TB ) is a common cause of mortality and morbidity in children infected with the human immunodeficiency virus ( HIV ) . Data on isoniazid preventive therapy ( IPT ) efficacy in HIV-infected children receiving antiretroviral therapy ( ART ) are inconclusive . OBJECTIVE To assess the efficacy , tolerability and safety of isoniazid ( INH ) in HIV-infected children on ART . DESIGN A pilot r and omised controlled study of INH was undertaken in HIV-infected children on ART . The primary outcome measure was TB disease or death . RESULTS A total of 167 children were r and omised to receive INH ( n = 85 ) or placebo ( n = 82 ) , and followed for a median of 34 months ( interquartile range [ IQR ] 24 - 52 ) . The median age was 35 months ( IQR 15 - 65 ) . There was one death in a child on INH and none in the placebo group . Eleven ( 6.6 % ) cases of TB occurred , 4 ( 5 % ) in the INH and 7 ( 9 % ) in the placebo group . Among the TB cases , 5 were culture confirmed-2 in the INH group and 3 in the placebo group , all susceptible to INH . Severe adverse events occurred rarely ( n = 6 ; 2 % ) . CONCLUSION IPT is safe and well tolerated in HIV-infected children on concomitant ART . This study supports the need for a larger study to assess efficacy in HIV-infected children living in TB-endemic areas BACKGROUND We studied the efficacy of a short-course regimen of chemotherapy for pulmonary tuberculosis in Kinshasa , Zaire . We also assessed whether , among patients with human immunodeficiency virus ( HIV ) infection , treatment should be extended from 6 to 12 months . METHODS HIV-seropositive and HIV-seronegative out patients with pulmonary tuberculosis were treated with rifampin , isoniazid , pyrazinamide , and ethambutol daily for two months , followed by rifampin plus isoniazid twice weekly for four months . The HIV-positive patients who had no evidence of tuberculosis were then r and omly assigned to receive either rifampin plus isoniazid or placebo twice weekly for a further six months . We also followed a comparison group of HIV-seronegative patients who received no further treatment for tuberculosis after six months . RESULTS After six months , 260 of 335 HIV-seropositive and 186 of 188 HIV-seronegative participants could be evaluated , and their rates of treatment failure were similar : 3.8 and 2.7 percent , respectively . At 24 months , the HIV-seropositive patients who received extended treatment had a relapse rate of 1.9 percent , as compared with 9 percent among the HIV-seropositive patients who received placebo for the second 6 months ( P < 0.01 ) . Extended treatment did not improve survival , however . Among the HIV-seronegative patients , 5.3 percent relapsed . CONCLUSIONS Among HIV-seropositive patients with pulmonary tuberculosis , extending treatment from 6 to 12 months reduces the rate of relapse but does not improve survival . The six-month program of partly intermittent antituberculous treatment may be an acceptable alternative when re sources are limited SETTING Two paediatric hospitals in Cape Town , South Africa . OBJECTIVE To investigate the incidence of and risk factors for severe liver injury in human immunodeficiency virus ( HIV ) infected children receiving long-term isoniazid preventive therapy ( IPT ) . DESIGN R and omised trial of IPT or placebo given daily or thrice weekly to HIV-infected children aged ≥8 weeks ; placebo was discontinued early . Alanine transaminase ( ALT ) was measured at baseline , 6-monthly and during illness : an increase of ≥10 times the upper limit of normal defined severe liver injury . RESULTS Of 324 children enrolled , 297 ( 91.6 % ) received IPT ( 559.1 person-years [ py ] ) . Baseline median age was 23 months ( interquartile range [ IQR ] 9.5 - 48.6 ) and median CD4 % , 20 % ( IQR 13.6 - 26.9 ) . A total of 207 ( 63.9 % ) children received combination antiretroviral therapy : 19 developed severe liver injury , 16 while receiving IPT . Among these there were 8 cases of viral hepatitis ( 5 with hepatitis A ) , 2 antiretroviral-induced liver injuries and 1 case of abdominal tuberculosis . IPT-related severe liver injury occurred in 1.7 % ( 5/297 , 0.78/100 py ) . No child developed hepatic failure ; one died of an unrelated cause . All surviving children subsequently tolerated IPT . CONCLUSIONS This study suggests that long-term IPT has a low toxicity risk in HIV-infected children . In the absence of chronic viral hepatitis , IPT can be safely re-introduced following recovery from liver injury SETTING Four human immunodeficiency virus ( HIV ) clinics located at South African tertiary hospitals . OBJECTIVE To assess the effectiveness of highly active antiretroviral therapy ( HAART ) in reducing incident tuberculosis ( TB ) in HIV-infected children . DESIGN Retrospective cohort . RESULTS A total of 1132 children 's records were included in the study . At entry to the cohort , the median ( interquartile range [ IQR ] ) age , CD4 % , CD4 count and viral load of all children was respectively 6.3 years ( 4.1 - 8.8 ) , 15 % ( 9.0 - 22.2 ) , 576 cells/mm(3 ) ( 287 - 960 ) and 160 000 copies/ml ( 54 941.5 - 449 683 ) ; 75.9 % were started on HAART . The male : female ratio was 1:1 , and median follow-up time was 1.7 years . In children whose follow-up included both pre-HAART and on-HAART periods , the incidence of clinical ly diagnosed TB was respectively 21.1 per 100 person-years ( py ; 95%CI 18.2 - 24.4 ) and 6.4/100 py ( 95%CI 4.8 - 8.1 ) , and when restricted to confirmed cases , respectively 3.1/100 py ( 95%CI 2.2 - 4.2 ) and 0.8/100 py ( 95%CI 0.5 - 1.4 ) . Only 23 % of all cases of TB were microbiologically confirmed . Multivariate analyses showed that HAART reduced incident TB by approximately 70 % , both for confirmed and all TB cases . CONCLUSIONS In this high TB burden country , the incidence of diagnosis of TB in HIV-infected children is at least as high as that of adults . HAART reduces incident TB , but further prospect i ve TB preventive and diagnostic studies are urgently needed in children To determine the aetiology and outcome of pneumonia in human immunodeficiency virus (HIV)‐infected children , we prospect ively investigated 250 children hospitalized with pneumonia who were known or clinical ly suspected to be HIV‐positive , or who required intensive care support in Cape Town , South Africa . Blood culture , induced sputum or bronchoalveolar lavage nasopharyngeal aspirate and gastric lavage were performed . Of the total , 151 children ( 60.4 % ) were HIV‐infected . Pneumocystis carinii pneumonia ( PCP ) , occurring in 19 ( 7.6 % ) children ( 15 HIV‐positive ) , was the AIDS‐defining infection in 20.3 % . The incidence and type of bacteraemia ( 14.3 % ) were similar in HIV‐positive and HIV‐negative patients ; S. pneumoniae ( 5 % ) and S. aureus ( 2 % ) were the predominant isolates . Sputum or BAL cultures yielded bacteria in 145 of 243 ( 60 % ) specimens ; viruses were cultured in 37 ( 15.2 % ) . Bacterial prevalence ( including M. tuberculosis in 8 % ) and anti‐microbial resistance did not differ by HIV status except for S. aureus which was more common in HIV‐infected children . Thirty‐one ( 20 % ) HIV‐positive and 8 ( 8 % ) HIV‐negative children died [ RR 1.16 ( 95 % CI 1.05–1.28 ) , p= 0.008 ] ; using multiple logistic regression , PCP was the only risk factor for mortality ( p= 0.03 ) Objectives To investigate the impact of isoniazid prophylaxis on mortality and incidence of tuberculosis in children with HIV . Design Two centre prospect i ve double blind placebo controlled trial . Participants Children aged ≥8 weeks with HIV . Interventions Isoniazid or placebo given with co-trimoxazole either daily or three times a week . Setting Two tertiary healthcare centres in South Africa . Main outcome measures Mortality , incidence of tuberculosis , and adverse events . Results Data on 263 children ( median age 24.7 months ) were available when the data safety monitoring board recommended discontinuing the placebo arm ; 132 ( 50 % ) were taking isoniazid . Median follow-up was 5.7 ( interquartile range 2.0 - 9.7 ) months . Mortality was lower in the isoniazid group than in the placebo group ( 11 ( 8 % ) v 21 ( 16 % ) , hazard ratio 0.46 , 95 % confidence interval 0.22 to 0.95 , P=0.015 ) by intention to treat analysis . The benefit applied across Centers for Disease Control clinical categories and in all ages . The reduction in mortality was similar in children on three times a week or daily isoniazid . The incidence of tuberculosis was lower in the isoniazid group ( 5 cases , 3.8 % ) than in the placebo group ( 13 cases , 9.9 % ) ( hazard ratio 0.28 , 0.10 to 0.78 , P=0.005 ) . All cases of tuberculosis confirmed by culture were in children in the placebo group . Conclusions Prophylaxis with isoniazid has an early survival benefit and reduces incidence of tuberculosis in children with HIV . Prophylaxis may offer an effective public health intervention to reduce mortality in such children in setting s with a high prevalence of tuberculosis . Trial registration . Clinical Trials Transient worsening of tuberculous symptomatology and lesions following antituberculous therapy ( paradoxical response ) has previously been described as a rare occurrence . To determine the incidence of paradoxical responses in patients with AIDS and TB who are treated with antituberculous therapy and subsequently with combination antiretroviral therapy ( ARV ) , we conducted a prospect i ve study of 33 HIV-seropositive TB patients treated with anti-TB therapy and antiretroviral therapy ( Group 1 ) compared with 55 HIV-seronegative TB patients treated with anti-TB therapy ( Group 2 ) and 28 HIV-seropositive TB patients treated with anti-TB therapy but not on antiretrovirals ( historical control ; Group 3 ) . In Group 1 patients , paradoxical responses were temporally more related to the initiation of ARV than to the initiation of anti-TB therapy ( mean + /- SD : 15 + /- 11 d versus 109 + /- 72 d [ p < 0.001 ] ) and occurred much more frequently ( 12 of 33 ; 36 % ) compared with Group 2 ( 1 of 55 ; 2 % ) ( p < 0.001 ) or with Group 3 ( 2 of 28 ; 7 % ) ( p = 0.013 ) . The majority of patients who experienced paradoxical responses and received tuberculin purified protein derivative ( PPD ) in Group 1 had their tuberculin skin tests convert from negative to strongly positive after ARV . These observations suggest that a paradoxical response associated with enhanced tuberculin skin reactivity may occur after the initiation of ARV in HIV-infected TB patients . Furthermore , the skin test conversion after the initiation of ARV may have important public health implication Objectives : To determine the incidence , clinical manifestations and risk factors for immune reconstitution inflammatory syndrome ( IRIS ) in young children initiating highly active antiretroviral therapy ( HAART ) . Design : A prospect i ve cohort of antiretroviral-naïve HIV-infected children less than 24 months of age enrolled in a treatment strategies trial in Johannesburg , South Africa . Methods : Among 169 HIV-infected children initiating HAART , April 2005 to November 2006 , the records of 83 children suspected to have IRIS within 6 months of starting treatment were review ed to determine whether they met criteria for IRIS . Seven were excluded due to incomplete follow-up . Pretreatment and post-treatment characteristics of children with and without IRIS were compared . Results : Overall , 34/162 ( 21 % ) children developed IRIS at a median of 16 days ( range 7–115 days ) post-HAART initiation . Bacille Calmette-Guérin reaction was most common occurring in 24/34 ( 71 % ) children , primarily injection site lesions and /or ipsilateral axillary lymphadenitis with abscess . Other IRIS conditions ( not mutually exclusive ) included Mycobacterium tuberculosis ( n = 12 ) , cytomegalovirus pneumonia ( n = 1 ) , Streptococcus pneumonia sepsis ( n = 1 ) , and severe seborrheic dermatitis ( n = 1 ) . Children with IRIS were younger ( median age 7 vs. 10 months , P = 0.007 ) with a lower CD4 cell percentage ( median 13.9 vs. 19.2 , P = 0.009 ) at HAART initiation than controls . After 24 weeks on HAART , 62 % of IRIS cases vs. 28 % of controls had HIV RNA more than 400 copies/ml ( P = 0.001 ) , odds ratio = 2.88 ( 95 % confidence interval = 1.14–7.29 ) after adjusting for baseline factors . Conclusion : Infants and young children with advanced HIV disease initiating HAART are at high risk for developing IRIS , leading to additional morbidity and possibly impairing virologic response to antiretroviral treatment CONTEXT Tuberculosis preventive therapy reduces tuberculosis incidence among human immunodeficiency virus (HIV)-infected individuals in clinical trials , but implementation has been limited and there are no data on effectiveness under routine conditions . OBJECTIVE To determine the effect on tuberculosis incidence of a clinic providing isoniazid preventive therapy to HIV-infected adults under routine conditions . DESIGN , SETTING , AND PARTICIPANTS R and omized intervention study with a novel incremental recruitment design . Between 1999 and 2001 ( before antiretroviral therapy was available ) , 1655 HIV-infected male employees of a South African gold-mining company ( median age , 37 years ) were enrolled in the study . Median follow-up was 22.1 months . INTERVENTION Employees were invited in r and om sequence to attend a workplace HIV clinic . Isoniazid , 300 mg/d , was self-administered for 6 months among attendees with no evidence of active tuberculosis . MAIN OUTCOME MEASURE Incidence of tuberculosis ( including both first and recurrent episodes ) during the periods before and after clinic enrollment . RESULTS A total of 1016 of 1655 men included in the analysis attended the clinic at least once . Six hundred seventy-nine ( 97 % ) of 702 men eligible to start primary isoniazid preventive therapy did so . The tuberculosis incidence rate before vs after clinic enrollment was 11.9 vs 9.0 per 100 person-years , respectively ( incidence rate ratio [ IRR ] after adjustment for calendar period , 0.68 ; 95 % confidence interval [ CI ] , 0.48 - 0.96 ) . In a multivariable analysis adjusting for calendar period , age , and silicosis grade , the tuberculosis IRR for clinic enrollment was 0.62 ( 95 % CI , 0.43 - 0.89 ) . In a further analysis excluding individuals with a history of tuberculosis ( and , hence , ineligible for isoniazid preventive therapy ) , the adjusted IRR for clinic enrollment was 0.54 ( 95 % CI , 0.35 - 0.83 ) . CONCLUSIONS Enrollment in a clinic offering primary isoniazid preventive therapy to HIV-infected adults reduced tuberculosis incidence by 38 % overall and by 46 % among individuals with no history of tuberculosis prior to the study . Tuberculosis incidence remained high despite isoniazid preventive therapy , and further work is needed to determine how to use additional interventions most effectively to reduce morbidity and mortality due to tuberculosis in HIV-infected persons Objective : To assess the impact of HIV infection upon the development , clinical presentation , and outcome of tuberculosis ( TB ) among children . Design : Case-control study and prospect i ve cohort study . Methods : From March 1994 to November 1995 , children aged 0–9 years with newly diagnosed TB were enrolled at the two outpatient TB centers and the two principal university hospitals in Abidjan , Côte d'Ivoire . Children were examined , blood sample s were collected for HIV serology and lymphocyte phenotyping , chest radiography was performed , and gastric aspirates and sputum sample s were collected for acid-fast bacilli smear and culture . Children were then followed every 2 months during a st and ard 6-month course of anti-TB therapy . To examine risk factors for TB , age- and sex-matched healthy control children were enrolled from among the siblings of children referred for TB skin testing . Results : Overall , 161 children with TB were enrolled , including 39 ( 24 % ) with culture-confirmed pulmonary TB , 80 ( 50 % ) with clinical ly diagnosed pulmonary TB , and 42 ( 26 % ) with extrapulmonary TB . Children with TB were significantly more likely than 161 control children to be HIV-seropositive ( 19 versus 0 % ) , to have a past TB contact ( 55 versus 16 % ) and to live in very low socioeconomic status housing ( 24 versus 6 % ) . No significant differences between HIV-seropositive and seronegative children were found in the distribution of radiologic abnormalities for pulmonary TB or in the site of extrapulmonary TB . The mortality rate in HIV-seropositive children was significantly higher than in seronegative children ( 23 versus 4 % ; relative risk , 3.6 ; 95 % confidence interval , 2.0–6.6 ) , and all deaths in HIV-seropositive children with available lymphocyte subtyping results occurred in those with a CD4 percentage of < 10 % . Conclusions : This study documents the importance of HIV infection as an independent risk factor for the development of TB in children , and demonstrates that HIV-related immunosuppression is a critical risk factor for mortality in this population An emergence of drug-resistant tuberculosis ( DR-TB ) in setting s affected by human immunodeficiency virus ( HIV ) and tuberculosis ( TB ) has been observed . We investigated the prevalence of DR-TB in P1041 , a multicentered , r and omised , double-blind trial which compared the administration of isoniazid ( INH ) to placebo , in HIV-exposed , non-infected and -infected African infants in the absence of any documented TB exposure . The prevalence of multidrug-resistant TB ( MDR-TB ) was 22.2 % ( 95%CI 8.5 - 45.8 ) and INH monoresistance 5.6 % ( 95%CI 0.1 - 27.6 ) among culture-confirmed cases , with all MDR-TB occurring in a single site . There was no association between INH treatment or placebo group , or between HIV infection status , and DR-TB prevalence . There was a high prevalence of DR-TB among HIV-exposed and -infected children . Surveillance of DR-TB among children in high-burden TB-HIV setting s should be routine |
13,843 | 29,280,712 | Synthesis of the articles suggests that self‐regulation ( e.g. , sensory processing , emotional regulation , executive functioning , social function ) improved with cognitive and occupation‐based interventions . | & NA ; This systematic review examines the evidence for the effectiveness of cognitive and occupation‐based interventions to improve self‐regulation in children and youth who have challenges in processing and integrating sensory information . | This study evaluated the effects of therapeutic horseback riding on social functioning in children with autism . We hypothesized that participants in the experimental condition ( n = 19 ) , compared to those on the wait-list control ( n = 15 ) , would demonstrate significant improvement in social functioning following a 12-weeks horseback riding intervention . Autistic children exposed to therapeutic horseback riding exhibited greater sensory seeking , sensory sensitivity , social motivation , and less inattention , distractibility , and sedentary behaviors . The results provide evidence that therapeutic horseback riding may be a viable therapeutic option in treating children with autism spectrum disorders BACKGROUND Unusual reactions to sensory input now form part of the diagnostic criteria for autism . These features are common and can have an often-devastating impact on autistic individuals and their families . Yet there are few vali date d interventions that help to remediate or support autistic individuals ' adverse sensory experiences . To date , both measurement of sensory experiences and the result ing interventions have been based on assumptions of neurological sensitivities and largely ignored the role of cognition . This study therefore sought to assess the feasibility of a new 8-week CBT-based group intervention for self-regulation of sensory processing difficulties . METHOD Seven cognitively able adolescents diagnosed with autism aged 11 - 16 years from one mainstream secondary school received the 8-week intervention . Measures of sensory reactivity , anxiety and repetitive behaviours were taken at baseline , post-intervention and follow-up , 8 weeks after the intervention had ceased . Semi-structured interviews and focus groups were also conducted with adolescents and their parents to examine further the acceptability of the intervention . RESULTS The results showed that the intervention itself was feasible - both in its implementation and its acceptability to participants . Qualitative analysis clearly showed that the intervention was effective in raising meta-conscious awareness and self-regulation in these autistic adolescents . Analysis of outcome variables showed no significant change over the intervention period , although effect sizes were moderate-to-large . CONCLUSIONS These preliminary results are encouraging and should inform the design of a future pilot r and omized controlled trial to test its efficacy with a larger group of participants ABSTRACT A multiple baseline across participants design was used to evaluate the effects of Social Stories to help preschool-aged children with characteristics of Autism Spectrum Disorders ( ASD ) increase their engagement in functional behaviors and use sensory integrative-based strategies to promote self-regulation . Three children , 3–5 years old , from a self-contained preschool classroom were selected to participate in the study . The intervention package included reading individualized Social Stories that discussed desired behaviors and self-regulation strategies . The research ers measured the percentage of intervals in which participants engaged in desired behaviors . The frequency of desired behaviors increased for all participants . The use of self-regulation strategies varied across participants . These findings suggest that the intervention was successful in increasing desired behaviors of the three children . Further research is recommended on the effectiveness of embedding sensory integrative strategies into Social Stories . Practitioners may consider the use of Social Stories as a tool to increase independence and encourage self-regulated behaviors in children with characteristics of ASD |
13,844 | 28,593,798 | Our study indicates significant nocebo in trials for MND treatment , adversely affecting adherence and efficacy of current treatments in clinical practice , with additional implication s for trial design | INTRODUCTION Nocebo is very prevalent among neurological disorders , result ing in low adherence and treatment outcome .
We sought to examine the AEs following placebo administration in placebo-controlled r and omised clinical trials ( RCTs ) for motor neuron disease ( MND ) . | Background Adjuvant endocrine therapy can improve disease-free survival and time before recurrence in breast cancer patients . However , it is associated with considerable side effects that negatively affect patients ’ quality of life and cause non-adherence . The recently demonstrated effect of individual expectations on side-effect development ( nocebo effect ) suggests that psychological factors play a role in the prevention of side effects . The aim of this study is to evaluate cognitive-behavioral side-effect prevention training ( SEPT ) for breast cancer patients . This article describes the study protocol and applied research methods . Methods / Design In a r and omized controlled trial , 184 female breast cancer patients are assigned to receive either SEPT , st and ard medical care or a manualized supportive therapy at the start of adjuvant endocrine treatment . SEPT consists of three sessions of cognitive-behavioral training including psychoeducation to provide a realistic view of endocrine therapy , imagination-training to integrate positive aspects of medication into daily life , and side-effect management to enhance expectations about coping ability . Side effects three months after the start of endocrine therapy serve as primary outcomes . Secondary outcomes include quality of life , coping ability and patients ’ medication adherence . Patients ’ expectations ( i.e. , expectations about side effects , coping ability , treatment and illness ) are analyzed as mediators . Discussion The optimization of expectations might be a potential pathway in health care to improve patients ’ quality of life during long-term medication intake . The results will provide implication s for a possible integration of evidence -based prevention training into clinical practice .Trial registration Clinical Trials.gov , ( NCT01741883 ) We initiated a double-blind , placebo-controlled trial to test the efficacy and safety of branched-chain amino acids ( BCAA ) ( L-leucine 12 g , L-isoleucine 6 g , and L-valine 6 g daily ) in amyotrophic lateral sclerosis ( ALS ) patients . There was an excess mortality in subjects r and omized to active treatment ( 24 BCAA , 13 placebo ) when a total of 126 ALS patients had been recruited . This finding , associated with the lack of efficacy of BCAA ( measured by comparing the disability scales in the two treatment groups ) , led the Data Monitoring Committee to require cessation of the trial BACKGROUND Amyotrophic lateral sclerosis ( ALS ) is a progressive disease with no effective treatment . In an initial study , riluzole decreased mortality and slowed muscle-strength deterioration in ALS patients . We have carried out a double-blind , placebo-controlled , multicentre study to confirm those findings and to assess drug efficacy at different doses . METHODS 959 patients with clinical ly probable or definite ALS of less than 5 years ' duration were r and omly assigned treatment with placebo or 50 mg , 100 mg , or 200 mg riluzole daily ; r and omisation was stratified by centre and site of disease onset ( bulbar or limb ) . The primary outcome was survival without a tracheostomy . Secondary outcomes were rates of change in functional measures ( muscle strength , functional status , respiratory function , patient 's assessment s of fasciculation , cramps , stiffness , and tiredness ) . The primary analysis was the comparison of the 100 mg dose with placebo by intention-to-treat . Drug-effect on survival was assessed before ( log-rank test ) and after adjustment for known prognostic factors ( Cox 's model ) . FINDINGS At the end of the study , after median follow-up of 18 months , 122 ( 50.4 % ) placebo-treated patients and 134 ( 56.8 % ) of those who received 100 mg/day riluzole were alive without tracheostomy ( unadjusted risk 0.79 , p = 0.076 ; adjusted risk 0.65 , p = 0.002 ) . In the groups receiving 50 mg and 200 mg riluzole daily , 131 ( 55.3 % ) and 141 ( 57.8 % ) patients were alive without tracheostomy ( relative to placebo 50 mg adjusted risk 0.76 , p = 0.04 ; 200 mg 0.61 , p = 0.0004 ) . There was a significant inverse dose response in risk of death . No functional scale discriminated between the treatment groups . The most common adverse reactions were asthenia , dizziness , gastrointestinal disorders , and rises in liver enzyme activities ; they were commonest with the 200 mg dose . INTERPRETATION Overall , efficacy and safety results suggest that the 100 mg dose of riluzole has the best benefit-to-risk ratio . This study confirms that riluzole is well tolerated and lengthens survival of patients with ALS BACKGROUND The cause of amyotrophic lateral sclerosis ( ALS ) is not known , and there is no effective treatment . Cell death may be caused by oxidative damage . Selegiline hydrochloride ( Eldepryl ) is a monoamine oxidase-B inhibitor with antioxidant properties . OBJECTIVE To determine if selegiline affects the clinical course of patients with ALS . DESIGN Six-month , double-blind , placebo-controlled study of 133 patients with classical ALS and symptoms for less than 3 years . The primary end point to indicate effectiveness was the rate of change of the Appel ALS total score , an index of disease severity that incorporates strength and function in limbs , respiratory function , and bulbar function . RESULTS Of the 133 patients , 67 were r and omized to receive selegiline and 66 to receive placebo . One hundred four patients ( 53 in the selegiline group and 51 in the placebo group ) completed the 6-month trial . Both groups were comparable for baseline characteristics and mean Appel ALS total score ( 70.5 points for the selegiline group and 70.6 for the placebo group ) . There was no difference in the rate of progression as measured by the Appel ALS total score , showing an average increase of 22 points in 6 months . The monthly rate of change was 3.4 for the selegiline group and 3.5 for the placebo group . There was 1 adverse reaction : worsening depression . Seven patients died during the study ( 4 in the selegiline group and 3 in the placebo group ) . CONCLUSION Selegiline treatment had no significant effect on the rate of clinical progression or outcome of ALS Abstract Treatment with the neuroprotective drug riluzole has previously been shown to increase the probability of survival in patients with amyotrophic lateral sclerosis . This report describes a placebo-controlled , double-blind r and omised clinical trial of riluzole carried out in ALS patients with advanced stage disease or aged over 75 years . The primary objective was to enable access to treatment to patients excluded from the pivotal trial which was run in parallel . Another goal was to assess the safety of riluzole in patients with advanced-stage disease . One hundred and sixty-eight patients were included , r and omised to either riluzole 50 mg b. i. d. or to placebo , and treated for eighteen months . Riluzole was well-tolerated in this patient population , and the adverse events observed were similar in nature and frequency to those observed in previously published clinical trials in patients included in pivotal trials . The study could not include enough patients to reach adequate power to detect differences in survival between the two treatment groups , and no such difference was in fact observed . In conclusion , riluzole is well-tolerated in ALS patients with advanced stage disease Ciliary neurotrophic factor ( CNTF ) is a neuroactive cytokine found in Schwann cells , which appears to be released in response to nerve injury . The ALS CNTF Treatment Study ( ACTS ) clinical trial was a phase II-III r and omized , placebo-controlled , double-blind study design ed to evaluate the safety , tolerability , and efficacy of subcutaneous administration of recombinantly produced human CNTF ( rHCNTF ) in slowing disease progression in 730 patients with amyotrophic lateral sclerosis ( ALS ) . Patients were r and omized to receive 30 micrograms/kg or 15 micrograms/kg rHCNTF or placebo subcutaneously three times a week for 9 months . The primary endpoint of the study , the slope of decline of isometric muscle strength in treated versus placebo patients , showed no statistically significant difference between rHCNTF and placebo-treated patients , and was complicated by an initial statistically significant decrease in strength early in rHCNTF-treated patients . Mortality was similar in all three study arms . There were no statistically significant treatment effects among the secondary measures . Side effects of rHCNTF included anorexia , weight loss , and cough and were sufficient to limit dosing in many patients & NA ; Discovery of the involvement of endogenous opiates in placebo analgesia represents an important step in underst and ing the mechanisms underlying placebo response . In the present study , we investigated the effects of the opiate antagonist naloxone and the cholecystokinin antagonist proglumide on placebo analgesia in a human model of experimentally induced ischemic pain . First , we found that part of the placebo response was reversed by naloxone , confirming previous studies on the role of opioids in the placebo phenomenon . Second , since it was demonstrated that the action of exogenous and endogenous opiates is potentiated by proglumide , we analysed the effects of this cholecystokinin antagonist on placebo response and found that it enhanced placebo analgesia . The placebo effect can thus be modulated in two opposite directions : it can be partially abolished by naloxone and potentiated by proglumide . The fact that placebo potentiation by proglumide occurred only in placebo responders , but not in non‐responders , suggests that activation of an endogenous opiate system is a necessary condition for the action of proglumide . These results suggest an inhibitory role for cholecystokinin in placebo response , although the low affinity of proglumide for cholecystokinin receptors does not rule out the possibility of other mechanisms We design ed a phase II trial to evaluate the efficacy of gabapentin in slowing the rate of decline in muscle strength of patients with amyotrophic lateral sclerosis ( ALS ) and to assess safety and tolerability . Gabapentin ( 800 mg ) or placebo was administered t.i.d . in a r and omized , double-blinded , placebo-controlled , trial for 6 months . We enrolled 152 patients at eight sites in the United States . The primary outcome measure was the slope of the arm megascore , the average maximum voluntary isometric strength from eight arm muscles st and ardized against a reference ALS population . A secondary outcome measure was forced vital capacity . Slopes of arm megascores for patients on gabapentin were compared with slopes of those taking placebo using a two-way ANOVA . We observed a nonstatistically significant trend ( p = 0.057 - 0.08 ) toward slower decline of arm strength in patients taking gabapentin compared with those taking placebo ( mean difference 24 % , median 37 % ) . We observed no treatment effect on forced vital capacity . Gabapentin was well tolerated by patients with ALS . These results suggest that further studies of gabapentin in ALS are warranted Background : Pre clinical and clinical studies of gabapentin in patients with ALS led the authors to undertake a phase III r and omized clinical trial . Methods : Patients were r and omly assigned , in a double-blinded fashion , to receive oral gabapentin 3,600 mg or placebo daily for 9 months . The primary outcome measure was the average rate of decline in isometric arm muscle strength for those with two or more evaluations . Results : Two hundred four patients enrolled , 196 had two or more evaluations , and 128 patients completed the study . The mean rate of decline of the arm muscle strength was not significantly different between the groups . Moreover , there was no beneficial effect upon the rate of decline of other secondary measures ( vital capacity , survival , ALS functional rating scale , timed walking ) nor was there any symptomatic benefit . In fact , analysis of the combined data from the phase II and III trials revealed a significantly more rapid decline of forced vital capacity in patients treated with gabapentin . Conclusion : These data provide no evidence of a beneficial effect of gabapentin on disease progression or symptoms in patients with ALS Calcium channel blocking drugs antagonize excitatory amino acid receptor activation , decrease calcium entry into damaged neurons , and might help to slow or reverse amyotrophic lateral sclerosis ( ALS ) . We enrolled 87 patients with ALS in a r and omized , placebo-controlled , prospect i ve , double-blind crossover study of nimodipine therapy . Monthly measures of isometric muscle strength and respiratory function compared the effects of drug and placebo . No difference in adverse events occurred in placebo vs drug-treated patients , but diarrhoea , nausea , and lightheadedness were more common with nimodipine . There was no significant difference in the rate of decline of pulmonary function or limb strength during treatment with drug or placebo . Nimodipine was ineffective in slowing the progress of ALS BACKGROUND Amyotrophic lateral sclerosis is a progressive motor neuron disease for which there is no adequate treatment . Some research suggests that the excitatory amino acid neurotransmitter glutamate may be involved in the pathogenesis . METHODS To evaluate the efficacy and safety of the antiglutamate agent riluzole , we conducted a prospect i ve , double-blind , placebo-controlled trial in 155 out patients with amyotrophic lateral sclerosis . The dose of riluzole was 100 mg per day . R and omization was stratified according to the site of disease onset ( the bulbar region or the limbs ) . The primary end points were survival and rates of change in functional status . The main secondary end point was change in muscle strength . Analyses were undertaken after 12 months of treatment and at the end of the placebo-controlled period ( median follow-up , 573 days ) . RESULTS After 12 months , 45 of 78 patients ( 58 percent ) in the placebo group were still alive , as compared with 57 of 77 patients ( 74 percent ) in the riluzole group ( P = 0.014 ) . For patients with bulbar-onset disease , one-year survival rates were 35 percent ( 6 of 17 ) with placebo and 73 percent ( 11 of 15 ) with riluzole ( P = 0.014 ) , whereas for those with limb-onset disease one-year survival was 64 percent and 74 percent , respectively ( P = 0.17 ) . The survival advantage with riluzole was smaller ( 37 percent [ 29 of 78 ] with placebo vs. 49 percent [ 38 of 77 ] with riluzole ) at the end of the placebo-controlled period , but it remained significant in the overall population ( P = 0.046 ) as well as in the patients with bulbar-onset disease ( 18 percent [ 3 of 17 ] vs. 53 percent [ 8 of 15 ] , P = 0.013 ) . The deterioration of muscle strength was significantly slower in the riluzole group than in the placebo group ( P = 0.028 ) . Adverse reactions to riluzole included asthenia , spasticity , and mild elevations in aminotransferase levels . Twenty-seven patients in the riluzole group withdrew from the study , as compared with 17 in the placebo group . CONCLUSIONS The antiglutamate agent riluzole appears to slow the progression of amyotrophic lateral sclerosis , and it may improve survival in patients with disease of bulbar onset |
13,845 | 22,032,440 | Prostagl and in E2 ( PGE2 ) and vaginal misoprostol were more effective than oxytocin in bringing about vaginal delivery within 24 hours but were associated with more uterine hyperstimulation .
Mechanical methods reduced uterine hyperstimulation compared with PGE2 and misoprostol , but increased maternal and neonatal infectious morbidity compared with other methods .
Membrane sweeping reduced post-term gestations .
Conclusions Research is needed to determine benefits and harms of many induction methods | Background Rates of labour induction are increasing .
We conducted this systematic review to assess the evidence supporting use of each method of labour induction . | Aim : To evaluate the efficacy of sweeping of fetal membranes for induction of labor in uncomplicated term pregnancies . Methods : A r and omized controlled trial was performed in 122 pregnant women beyond 39 weeks of gestation with no complications . The women were assigned to have their membranes swept or not ( controls ) for labor induction . The main outcome measures included duration of pregnancy and possible complications of sweeping of membranes , including rupture of membranes , postpartum infections , and vaginal bleeding . Results : Twenty-one patients did not give birth in our hospital and were , therefore , excluded from the study ; 101 women completed the study ( 51 patients in the control group and 50 women in the study group ) . There were no statistically significant differences in maternal age , parity , birth weight , and Bishop score in the two groups . The mean interval between sweeping ( stripping ) and vaginal examination until delivery was 7.7 ± ( SD ) 6.9 and 7.1 ± 5.6 days in the sweeping and in the control group , respectively ( p = 0.61 ) . Of the 101 pregnant women , only 6 patients had premature rupture of membranes ( 2 in the sweeping group and 4 in the control group ) . There were no statistically significant differences between these individuals ( p = 0.68 ) . Significant vaginal bleeding was not observed in the two groups . Meconium-stained amniotic fluid was seen in 13 women : 8 in the sweeping group and 5 in the control group . There were no statistically significant differences among the women who had meconium-stained fluid in case and control groups ( p = 0.39).There were no differences between women who had puerperal fever ( 3 in the sweeping group and 2 in the control group ; p = 0.68).12 of the 101 women ( 6 in each group ) had cesarean section performed , but there was no difference betweeen the two groups . Conclusion : Sweeping of membranes at 39 weeks of gestation has no significant clinical effect on the duration of pregnancy Objective . To compare effectiveness and safety of 25 μg vaginal misoprostol versus Foley catheter and oxytocin for cervical ripening and labor induction in pregnant women with unripe cervices . Design . R and omized controlled trial . Setting . A public maternity in Recife , Brazil . Sample . A total of 240 pregnant women . Methods . Women with a term or post‐term , live , singleton fetus in cephalic presentation , intact membranes , Bishop score < 6 , not in labor , medically indicated for labor induction . They were r and omly divided in Group 1 , where 119 women received 25 μg of intravaginal misoprostol every 6 hours for a maximum of four doses ; and Group 2 , where 121 women had a 14‐F Foley catheter inserted into their cervical canal . Once past the internal os , the balloon was inflated . Intravenous oxytocin was initiated after the balloon was spontaneously extruded from the cervix or after 24 hours . Results . There were no significant differences between the groups regarding baseline characteristics . Misoprostol was more effective in inducing labor than Foley catheter and oxytocin . Mean induction‐to‐vaginal delivery time with misoprostol was shorter ( 17.3 vs. 20.2 hours , p = 0.016 ) . There were more vaginal deliveries in the misoprostol group at 12 ( p < 0.001 ) and 18 ( p = 0.007 ) hours , but the difference was no longer statistically significant at 24 and 48 hours . There were no significant differences in uterine contraction abnormalities , puerperal infection or neonatal outcomes . Conclusions . Vaginal misoprostol is more effective than and as safe as Foley catheter and oxytocin for induction of labor in term and post‐term pregnancy OBJECTIVE : To estimate if membrane sweeping increases the rate of prelabor rupture of membranes . METHODS : This r and omized trial of term , uncomplicated pregnancies included 300 patients . Patients were r and omly assigned into sweep or no-sweep groups , with patients and delivering providers blinded to group allocation . Only the examining provider in the clinic was unblinded to group allocation . Membranes were then swept or not swept at each weekly visit from 38 weeks of gestation onward , depending on the r and omization . Data collected included parity , cervix examination at each visit , estimated gestational age at delivery , rupture of membranes , and maternal or fetal complications . RESULTS : A total of 162 patients were r and omly assigned to the membrane sweep group and 138 to the no-sweep group . There was no difference in baseline characteristics or obstetric and neonatal outcomes between the groups . The average gestational age at delivery and induction rate were not different . The overall prelabor rupture of membranes rate was not significantly higher in the membrane sweep group ( 12 % compared with 7 % ) ( P=.19 ) ; however , patients with a cervix more than 1 cm dilated at time of membrane sweeping were more likely to have prelabor rupture of membranes if they were in the membrane sweep group ( 9.1 % compared with 0 % ; relative risk 1.10 , 95 % confidence interval 1.03–1.18 ) . CONCLUSION : No benefit in gestational age at delivery or reduction of postmaturity occurred from membrane sweeping . Although the overall prelabor rupture of membranes rates were similar , patients with membrane sweeping occurring at more than 1 cm cervical dilation may be at increased risk of prelabor rupture of membranes . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , www . clinical trials.gov , NCT00294242 LEVEL OF EVIDENCE : Objective . To evaluate the efficacy of acupuncture for labor stimulation . Methods . Nulliparous women at 38 weeks or greater were r and omized to traditional Chinese medicine ( TCM ) acupuncture , sham acupuncture , or usual care only groups . Acupuncture points LI4 , SP6 , BL32 , and BL54 were needled bilaterally . The primary outcome was time from enrollment to delivery . Secondary outcomes included rates of spontaneous labor and cesarean delivery . Medical records were abstract ed for maternal demographic , medical , and delivery outcome data . ANOVA , Student 's t-test , Chi-square , and Kaplan – Meier statistics were used to compare groups . Results . Eighty-nine women were enrolled and r and omized . Maternal age , gestational age , prior acupuncture experience , tobacco , alcohol and drug use , gravida , and history of gynecological surgery were similar among the groups . There were no statistically significant differences among groups for time from enrollment to delivery ( p = 0.20 ) , rates of spontaneous labor ( p = 0.66 ) , or rates of cesarean delivery ( p = 0.37 ) . Rates of maternal and neonatal outcomes were not significantly different . Conclusion . TCM acupuncture was not effective in initiating spontaneous labor or reducing the rate of cesarean delivery compared with sham acupuncture or usual medical care Please cite this paper as : Modlock J , Nielsen B , Uldbjerg N. Acupuncture for the induction of labour : a double‐blind r and omised controlled study . BJOG 2010;117:1255–1261 OBJECTIVE : To estimate the effect of serial membrane sweeping on the onset of labor in women who planned vaginal birth after cesarean ( VBAC ) . METHODS : Women at term with one transverse lower segment cesarean delivery who were suitable for and who planned VBAC were approached to participate . Participants were r and omly assigned to weekly membrane sweeping or weekly vaginal assessment for Bishop score until delivery . Participants and delivery providers were blinded to the allocated treatment . St and ard obstetric care was given to all participants . The primary outcome was onset of labor which was defined as the presence of spontaneous regular and painful contractions that cause cervical dilation to at least 3 cm or prelabor rupture of membranes . Secondary outcomes included induction of labor and repeat cesarean delivery . RESULTS : One hundred eight women were r and omly assigned to membrane sweeping and 105 to control . The spontaneous labor rate was 78.5 % compared with 72.1 % ( relative risk [ RR ] 1.1 , 95 % confidence interval [ CI ] 0.9–1.3 ; P=.34 ) , the induction of labor rate was 12.1 % compared with 9.6 % ( RR 1.3 , 95 % CI 0.6–2.8 ; P=.66 ) , and the all-cause cesarean delivery rate was 40.2 % compared with 44.2 % ( RR 0.9 , 95 % CI 0.7–1.2 ; P=.58 ) for the membrane sweeping and control groups , respectively . Gestational age at delivery ( mean±st and ard deviation ) of 39.6±1.0 weeks for the membrane sweeping group compared with 39.6±0.9 weeks for the control group ( P=.84 ) was no different . CONCLUSION : Serial membrane sweeping at term in women who planned VBAC has no significant effect on the onset of labor , pregnancy duration , induction of labor , or repeat cesarean delivery . CLINICAL TRIAL REGISTRATION : IS RCT N , is rct n.org , IS RCT N55163179 . LEVEL OF EVIDENCE : OBJECTIVE To compare the efficacy and safety of oral misoprostol with intracervical prostagl and in E2 ( PGE2 ) gel for the active management of premature rupture of membranes ( PROM ) at term . METHODS Women with pregnancies between 37 and 42 weeks presenting with PROM at term and a Bishop score of 5 or less were r and omly assigned to receive either a 4-hourly oral dose of 50 microg of misoprostol up to a maximum of 3 doses or 2 applications of intracervical PGE2 gel at a 6-hour interval . Oxytocin was given if labor had not started after 12 hours . RESULTS Twenty women in the misoprostol group ( n=31 ) delivered within 12 hours compared with 5 in the PGE2 group ( n=30 ) ( P<0.001 ) . The induction-to-delivery interval in the misoprostol group was shorter than in the PGE2 gel group ( 615 min vs 1070 min ; P<0.001 ) . The mode of delivery was comparable between the 2 groups ( P=0.821 ) . Abnormalities in uterine contractions and neonatal outcomes were also comparable . The requirement for oxytocin was lower and patient satisfaction was better in the misoprostol group . CONCLUSION Oral misoprostol is a safe and efficacious alternative to intracervical PGE2 gel in the active management of PROM at term OBJECTIVE : To estimate the clinical effectiveness of acupuncture to induce labor . METHODS : This study was a r and omized controlled trial of acupuncture compared with sham acupuncture . Women who were scheduled for a postterm induction with a singleton pregnancy and cephalic presentation were eligible for the study . Women received two acupuncture or sham acupuncture sessions over a 2-day period before the planned medical/pharmacological induction . The principal primary outcomes related to the need for induction methods and time from the administration of the intervention to delivery . RESULTS : Three hundred sixty-four women were r and omly assigned to the trial ( treatment n=181 and control n=183 ) . Women did not differ in their need for induction methods between groups : prostagl and in induction : relative risk ( RR ) 1.20 , 95 % confidence interval ( CI ) 0.96–1.51 , P=.11 ; artificial rupture of membranes only : RR 0.93 , 95 % CI 0.72–1.20 , P=.57 ; oxytocin only : RR 0.89 , 95 % CI 0.60–1.32 , P=.55 ; artificial rupture of membranes plus oxytocin : RR 0.87 , 95 % CI 0.57–1.33 , P=.52 ; prostagl and ins , artificial rupture of membranes , and oxytocin : RR 0.84 , 95 % CI 0.37–1.91 , P=.68 . The median time from acupuncture to delivery was 68.6 hours ( interquartile range 53.9–79.5 ) compared with 65 hours ( interquartile range 49.3–76.3 ) for women in the control group . CONCLUSION : Two sessions of manual acupuncture , using local and distal acupuncture points , administered 2 days before a scheduled induction of labor did not reduce the need for induction methods or the duration of labor for women with a postterm pregnancy . CLINICAL TRIAL REGISTRATION : Australian New Zeal and Clinical Trials Registry , www.anzctr.org.au , ACTRN12606000494538 LEVEL OF EVIDENCE : OBJECTIVE To evaluate the effectiveness of membrane sweeping at 41 weeks for the prevention of post-term pregnancy . DESIGN A multicentre r and omised controlled trial . SETTING Fifty-one primary care midwifery practice s in the Netherl and s. POPULATION A total of 742 low-risk pregnant women at 41 weeks of gestation . METHODS Participants were r and omly assigned to serial sweeping of the membranes ( every 48 hours until labour commenced up to 42 weeks of gestation ) or no intervention . MAIN OUTCOME MEASURES Post-term pregnancy ( > or=42 weeks ) . Subgroup analyses were performed on nulliparous and parous women . Secondary outcomes included adverse effects . RESULTS Serial sweeping of the membranes at 41 weeks decreased the risk of post-term pregnancy ( 87/375 [ 23 % ] versus 149/367 [ 41 % ] ; relative risk [ RR ] 0.57 , 95 % CI 0.46 - 0.71 ; number needed to treat [ NNT ] 6 [ 95 % CI 4 - 9 ] ) . Benefits were also seen in both subgroups ( nulliparous : 57/198 [ 29 % ] versus 89/192 [ 46 % ] ; RR 0.62 [ 95 % CI 0.48 - 0.81 ] ; NNT 6 [ 95 % CI 4 - 12 ] and parous : 30/177 [ 17 % ] versus 60/175 [ 34 % ] ; RR 0.49 [ 95 % CI 0.34 - 0.73 ] ; NNT 6 [ 95 % CI 4 - 6 ] ) . Adverse effects were similar in both the groups except for uncomplicated bleeding , which was reported more frequently in the sweeping group . Other obstetric outcomes and indicators of neonatal morbidity were similar in both groups . There were two perinatal deaths in each group . CONCLUSIONS Membrane sweeping at 41 weeks can substantially reduce the proportion of women with post-term pregnancy OBJECTIVES To compare the efficacy of labour induction using sublingual misoprostol versus combined artificial rupture of membranes and oxytocin infusion for nulliparous women with a favourable cervix at term . DESIGN Open r and omised controlled trial . SETTING Regional hospital , Hong Kong . PATIENTS Fifty nulliparous women with a favourable cervix ( Bishop score 6 or more ) at term and indications for labour induction . INTERVENTIONS With their informed consent , 100 eligible women were to be r and omised to receive either sublingual misoprostol 50 micrograms every 4 hours for up to five doses or oxytocin infusion after artificial rupture of membranes . Interim analysis was planned at a sample size of 50 . MAIN OUTCOME MEASURES Vaginal delivery within 24 hours of induction . RESULTS The study was terminated when interim analysis of the first 50 recruits showed that a significantly smaller proportion of misoprostol-treated women delivered vaginally within 24 hours of induction than in the conventional treatment group ( 68 % vs 100 % ; relative risk , 0.68 ; 95 % confidence interval , 0.51 - 0.91 ; P=0.009 ) , although comparable numbers of women eventually delivered vaginally . The mean induction to vaginal delivery interval was 4.5 hours longer in the misoprostol group ( P=0.027 ) . After misoprostol treatment , all women went into labour . Forty percent of them delivered without oxytocin . There was no significant difference in uterine hyperstimulation rate , operative delivery rate , and neonatal outcomes . Maternal satisfaction was higher in the misoprostol group ( 92 % vs 60 % ; relative risk , 1.53 ; 95 % confidence interval , 1.09 - 2.16 ; P=0.008 ) . CONCLUSIONS Despite being well accepted by women , labour induction using this regimen of sublingual misoprostol is less effective in achieving vaginal delivery within 24 hours BACKGROUND To assess if acupuncture influences the onset of labour and the need for induction after prelabour rupture of membranes ( PROM ) in nulliparous women . Further , to investigate a possible effect of acupuncture on the woman 's wellbeing . METHODS In a r and omised controlled trial ( RCT ) , 106 nulliparous women with PROM were allocated to an acupuncture group ( AG ) or a control group ( CG ) . The outcome measures were time from PROM to onset of active phase of labour , and rate of inductions if labour was absent after 2 days . The women 's self-reported wellbeing was registered on a Visual Analogue Scale ( VAS ) . RESULTS There was no statistically significant difference between the 2 groups regarding time from PROM to active phase ( median times in AG versus CG : 15 versus 20.5 h , p=0.34 ) . Additionally , there was no difference between the 2 groups in the need for induction . We found no significant differences in self-reported wellbeing , but the women receiving acupuncture considered their treatment to be more positive than the controls ( p=0.003 ) . No adverse effects were reported . CONCLUSIONS Acupuncture treatment used in nulliparas after PROM showed no significant effect in reducing time to active labour or in reducing rate of inductions . There was no change in wellbeing as a result of acupuncture , but it was considered positive to receive this kind of treatment while waiting for labour to begin OBJECTIVE The purpose of this study was to compare the efficacy and safety profile of prostagl and in E2 with isosorbide mononitrate for cervical ripening before the induction of labor at term . STUDY DESIGN Primigravid women were assigned r and omly to receive either 40 mg of isosorbide mononitrate or 2 mg of prostagl and in E2 . Efficacy outcomes were the cervical ripening effect of each agent and the time from treatment initiation to delivery . Safety outcomes were the incidence and frequency of maternal side effects and events that would be potentially hazardous for mother and baby during outpatient cervical ripening . RESULTS Prostagl and in E2 was more effective than isosorbide mononitrate in inducing a change in modified Bishop score . Mean duration from treatment initiation to delivery was greater for isosorbide mononitrate than prostagl and in E2 . There were no adverse events in the isosorbide mononitrate group that would contraindicate outpatient treatment . However , in the prostagl and in E2 group , 7 % of the pregnancies had abnormal fetal heart rate patterns ( P = .0002 ) . Maternal satisfaction was significantly higher in the isosorbide mononitrate group . CONCLUSION Although isosorbide mononitrate was less effective , maternal satisfaction was significantly greater . The safety profile of each agent was such that it would be reasonable to give isosorbide mononitrate , but not prostagl and in E2 , on an outpatient basis OBJECTIVE To examine the effectiveness and safety of outpatient vaginal administration of isosorbide mononitrate ( IMN ) to induce cervical ripening . METHODS A prospect i ve , double-blind , placebo-controlled , r and omized clinical trial was conducted on 102 singleton term pregnant women with unfavorable cervices who were r and omly assigned to receive outpatient intravaginal IMN or placebo before admission for induction of labor . The main outcome variable was time from hospital admission to delivery . Secondary outcomes included fetal and maternal morbidity , labor characteristics , and incidence of cesarean delivery . RESULTS The admission-delivery interval was 13.45+/-6.63 and 20.12+/-8.19 h ( P=0.0001 ) for the IMN and placebo groups , respectively . Of the IMN patients 62.75 % needed prostagl and ins for cervical ripening versus 90.2 % with placebo ( P=0.002 ) . The incidence of tachysystole was significantly lower in the IMN group ( P<0.05 ) but there were no significant differences in cesarean delivery rate , neonatal outcomes , and incidence of hyperstimulation . CONCLUSIONS Outpatient use of IMN result ed in shorter admission to delivery interval , and was associated with less prostagl and in use and lower incidence of uterine tachysystole Misoprostol is a synthetic prostagl and in E1 analogue that has been found to be as effective as dinoprostone and oxytocin in inducing labor . Different routes of administration of misoprostol have been tried effectively and recently the sublingual and vaginal routes of administration were compared . However more research is needed in this area . An open r and omized controlled clinical trial was conducted at the labor ward of Wad Medani Hospital Sudan to test the outcome of induction of labor using misoprostol administered via different routes . The study received ethical clearance from the Ethical Board of The University of Geizera Sudan . The women admitted from February through November 2006 to the labor ward were asked to participate in the study if they had a singleton pregnancy and a live fetus but an unfavorable cervix ( Bishop score 6 ) . The women were assigned toreceive 50 µg of misoprostol orally vaginally or sublingually . Outcome measures were induction to delivery time cesarean section rate Apgar score at 1 min presence of meconium-stained liquor and referral of the newborn to the pediatrician . ( excerpt Objective . To evaluate the efficacy of membrane sweeping at initiation of labor induction in low-risk patients at term pregnancy ( 38–40 gestational weeks ) . Methods . This prospect i ve study included 351 antenatal women who were r and omly assigned to one of two groups : a sweeping of the membranes group ( n = 181 ) and a no sweeping control group ( n = 170 ) . The primary outcome measure was the proportion of women who entered spontaneous labor within 1 week of entry into the study . Secondary outcome measures included mode of delivery and maternal and fetal complications . Results . Five patients ( two in the sweeping group and three in the no sweeping group ) were excluded from the study because of breech presentation at labor . There were no statistically significant differences between the two groups regarding maternal age , parity or Bishop score . The proportion of subjects who entered spontaneous labor before 41 weeks of gestation was significantly different between the two groups ( p < 0.0001 ) . The mode of delivery did not differ significantly between the groups and there was no statistically significant difference in maternal or fetal complications . Conclusions . Sweeping of membranes is a safe method to reduce the length of term in pregnancy and the incidence of prolonged gestation in a low-risk population . There is no evidence that sweeping the membranes increases the risk of maternal or neonatal adverse outcomes OBJECTIVE The aim of this study was to compare the efficacy and safety of a prostagl and in E(2 ) ( PGE(2 ) ) vaginal insert with those of oxytocin for labor induction . The present study also examined whether its use reduces the rate of cesarean delivery in term pregnancies with premature rupture of membranes ( PROM ) and low Bishop scores . MATERIAL S AND METHODS A total of 240 women with singleton pregnancies at > or= 37 weeks , no prior uterine scar , vertex presentations , reactive nonstress tests , PROM for > or= 12 hours and Bishop scores of < or= 6 were r and omly assigned to receive either oxytocin or vaginal PGE(2 ) . The primary outcomes were time from induction to delivery and mode of delivery . RESULTS The time from labor induction to active labor onset was significantly shorter in the oxytocin group than in the PGE(2 ) group ( 4.9 + /- 4.1 vs. 8.5 + /- 3.6 hours ; p = 0.02 ) . The time from induction to delivery was also significantly shorter in the oxytocin group ( 3.4 + /- 1.5 vs. 9.6 + /- 4.7 hours ; p = 0.02 ) . Cesarean delivery rates were statistically similar in the oxytocin and PGE(2 ) groups ( 18.3 vs. 20.0 % ; p = 0.81 ) . Neonatal outcomes were comparable in both groups . Comparable results were observed for nulliparous women included in the study population . CONCLUSION Oxytocin treatment seems to be superior to vaginal administration of PGE(2 ) to induce labor in term pregnancies complicated with PROM and unfavorable services |
13,846 | 23,350,761 | There are rather consistent findings that greater age , a more severe stroke ( measured through a clinical evaluation scale ) , the presence of urinary incontinence ( with impaired awareness ) and a larger stroke volume ( measured through brain imaging techniques ) predict poor stroke outcome .
Studies using a selected group of stroke patients tended to identify different predictors .
The current evidence is insufficient for the development of a clinical prediction tool that is better than physicians ' informal predictions . | PURPOSE To identify factors in the early post-stroke period that have a predictive value for a poor outcome , defined as institutionalization or severe disability .
In contrast to clinical expectations , the prognostic value of ADL-dependency and impaired cognition remains unclear , and factors in the domains of emotional and communicative functioning rarely feature . | Background and Purpose — Asymptomatic hemorrhagic transformation of infa rct ion ( AHTI ) is common , but its risk factors and relationship with functional outcome are poorly defined . Methods — The analyses used data from the Tinzapararin in Acute Ischaemic Stroke Trial , a r and omized controlled trial assessing tinzaparin ( low molecular weight heparin ) versus aspirin in 1484 patients with acute ischemic stroke . CT head scans ( baseline , day 10 ) were adjudicated for the presence of hemorrhagic transformation . Stroke subtype was classified according to modified Trial of Org 10172 in Acute Stroke Treatment ( small vessel , large vessel , cardioembolic ) and the Oxfordshire Community Stroke Project ( total anterior , partial anterior , lacunar , and posterior circulatory syndromes ) . Modified Rankin scale and Barthel Index were measured at 3 and 6 months . Analyses were adjusted for age , sex , severity , blood pressure , infa rct volume , and treatment . Symptomatic hemorrhage was excluded . Results — At day 10 , AHTI did not differ between aspirin ( 300 mg ; 32.8 % ) and medium-dose ( 100 IU/kg ; 36.0 % ) and high-dose ( 175 IU/kg ; 31.4 % ) tinzaparin groups ( P=0.44 ) . Relative to lacunar stroke , AHTI on follow-up CT was significantly increased in total anterior circulation syndrome ( odds ratio , 11.5 ; 95 % CI , 7.1 to 18.7 ) and partial anterior circulation syndrome ( odds ratio , 7.2 ; 95 % CI , 4.5 to 11.4 ) stroke . Similarly , relative to small vessel disease , AHTI was increased in large vessel ( odds ratio , 15.1 ; 95 % CI , 9.4 to 24.3 ) and cardioembolic ( odds ratio , 14.1 ; 95 % CI , 8.5 to 23.5 ) stroke . After adjustment for infa rct volume , the presence of AHTI was not associated with outcome at 3 or 6 months as measured by the modified Rankin Scale and Barthel Index . Conclusions — AHTI is increased in ischemic stroke with cortical syndromes and of large vessel or cardioembolic etiology . Heparin does not increase AHTI . AHTI is not associated with functional outcome BACKGROUND Urinary tract infection ( UTI ) is a recognized complication of stroke . We aim ed to determine the incidence of UTI after acute stroke , the risk factors associated with this complication , and its association with outcome . METHODS Prospect i ve study of consecutive acute stroke patients admitted to an urban teaching hospital . Routine clinical assessment included the modified National Institutes of Health Stroke Scale ( mNIHSS ) and modified Rankin scale ( mRS ) . Patients were followed up for 3 months , including recording of clinician diagnosis of UTI . RESULTS We studied 412 patients ; 65 ( 15.8 % ) were diagnosed with UTI , at a median of 14 days ( IQR = 4 - 39 ) post-stroke . In a binomial multivariate regression analysis , UTI was associated with urinary catheterization ( OR = 3.03 , 95 % CI 1.41 - 6.52 ) , higher mRS ( OR = 1.85 , 1.29 - 2.64 ) and increasing age ( OR = 1.51 , 1.13 - 2.00 for each decade ) . UTI was associated with death or disability at 3 months , however , this link was attenuated and became non-significant when measures of stroke severity and pre-stroke morbidity were included in a multivariate analysis . CONCLUSION UTI is common after acute stroke . It is associated with urinary catheterization , post-stroke disability and increasing age . Avoidance of catheterization might reduce the incidence of this common complication We sought to establish the pattern of blood pressure ( BP ) change after hospitalization for acute hemispheric stroke . Methods In 292 patients from the Leicester teaching hospitals with acute hemispheric stroke within the previous 24 hours ( 139 men ; median age , 75 years [ range , 42 to 98 years ] ) , we prospect ively studied BP changes between admission , 24 hours , 1 week , and 4 to 6 weeks . Changes were assessed in relation to the main stroke risk factors , stroke type and severity , and antihypertensive drug treatment . All subjects were followed up for 1 week , with 117 subjects followed up for 4 to 6 weeks . Changes were assessed by repeated- measures ANOVA , and Student 's t tests were used to compare group pairs . Results Systolic and diastolic BP fell by 12 mm Hg ( 95 % confidence interval [ CI ] , 8 to 15 mm Hg ) and 7 mm Hg ( 95 % CI , 5 to 9 mm Hg ) , respectively , in the first 24 hours and 22 mm Hg ( 95 % CI , 18 to 25 mm Hg ) and 12 mm Hg ( 95 % CI , 10 to 14 mm Hg ) , respectively , during the first week ( all changes significant at P<.01 ) but no further thereafter . In those patients receiving no antihypertensive medication before or after stroke , the pattern of change was similar to that of the whole group . Previously diagnosed hypertensive subjects ( n=106 ) had higher initial BP values than did normotensive subjects , although by 1 week the levels were not significantly different . Patients with cerebral hemorrhage confirmed by computed tomography ( n=20 ) had higher systolic BP , but not diastolic BP , throughout the first week than those with cerebral infa rct ion ( n=89 ) . The severity of stroke , age , and previous stroke history did not appear to alter the BP pattern . Stroke patients who were moderate to heavy alcohol consumers had lower convalescent systolic BP levels than lighter drinkers or abstainers . Conclusions We have demonstrated a marked fall in systolic and diastolic BP levels during the first 7 days after acute hemispheric stroke , with little change thereafter . Higher initial systolic BP values were found in patients with cerebral hemorrhage compared with those with cerebral infa rct . Moderate to heavy alcohol consumption before stroke was associated with a greater systolic BP decline in the first week after the event compared with stroke patients who were light drinkers or abstainers BACKGROUND AND PURPOSE Even patients with the most severe strokes sometimes experience a remarkably good recovery . We evaluated possible predictors of a good outcome to search for new therapeutic strategies . METHODS We included the 223 patients ( 19 % ) with the most severe strokes ( Sc and inavian Stroke Scale score < 15 points ) from the 1197 unselected patients in the Copenhagen Stroke Study . Of these , 139 ( 62 % ) died in the hospital and were excluded . The 26 survivors ( 31 % ) with a good functional outcome ( Barthel Index > /=50 points ) were compared with the 58 survivors ( 69 % ) with a poor functional outcome ( Barthel Index < 50 points ) . The predictive value of the following factors was examined in a multivariate logistic regression model : age ; sex ; a spouse ; work ; home care before stroke ; initial stroke severity ; blood pressure , blood glucose , and body temperature on admission ; stroke subtype ; neurological impairment 1 week after onset ; diabetes ; hypertension ; atrial fibrillation ; ischemic heart disease ; previous stroke ; and other disabling disease . RESULTS Decreasing age ( odds ratio [ OR ] , 0.50 per 10-year decrease ; 95 % CI , 0.25 to 0.99 ; P=0.04 ) , a spouse ( OR , 3.1 ; 95 % CI , 1.1 to 8 . 8 ; P=0.03 ) , decreasing body temperature on admission ( OR , 1.8 per 1 degrees C decrease ; 95 % CI , 1.1 to 3.1 ; P=0.01 ) , and neurological recovery after 1 week ( OR , 3.2 per 10-point increase in Sc and inavian Stroke Scale score ; 95 % CI , 1.1 to 7.8 ; P=0.01 ) were all independent predictors of good functional outcome . CONCLUSIONS Patients with the most severe strokes who achieve a good functional outcome are generally characterized by younger age , the presence of a spouse at home , and early neurological recovery . Body temperature was a strong predictor of good functional outcome and the only potentially modifiable factor . We suggest that a r and omized controlled trial be undertaken to evaluate whether active reduction of body temperature can improve the generally poor prognosis of patients with the most severe strokes BACKGROUND AND PURPOSE The great variability of outcome seen in stroke patients has led to an interest in identifying predictors of outcome . The combination of clinical and imaging variables as predictors of stroke outcome in a multivariable risk adjustment model may be more powerful than either alone . The purpose of this study was to determine the multivariable relationship between infa rct volume , 6 clinical variables , and 3-month outcomes in ischemic stroke patients . METHODS Included in the study were 256 eligible patients from the R and omized Trial of Tirilazad Mesylate in Acute Stroke ( RANTTAS ) . Six clinical variables and 1-week infa rct volume were the prespecified predictor variables . The National Institutes of Health Stroke Scale , Barthel Index , and Glasgow Outcome Scale were the outcomes . Multivariable logistic regression techniques were used to develop the model equations , and bootstrap techniques were used for internal validation . Predictive performance of the models was assessed for discrimination with receiver operator characteristic ( ROC ) curves and for calibration with calibration curves . RESULTS The predictive models had areas under the ROC curve of 0.79 to 0.88 and demonstrated nearly ideal calibration curves . The areas under the ROC curves were statistically greater ( P<0.001 ) with both clinical and imaging information combined than with either alone for predicting excellent recovery and death or severe disability . CONCLUSIONS Combined clinical and imaging variables are predictive of 3-month outcome in ischemic stroke patients . Demonstration of this relationship with acute clinical variables and 1-week infa rct information supports future attempts to predict 3-month outcome with all acute variables Objective : To ” nd patient characteristics in the early post stroke phase that could predict three years functional outcome . Design : Prospect i ve study . Setting : In-hospital rehabilitation department ( admission and discharge ) . Outpatient department one and three years post stroke . Subjects : One hundred and forty-two stroke patients ( 56 % women ) , median age 75 years . Main outcome measures : Barthel Index ( BI ) score ; BI score change ; accommodation status ; Rankin scale score ; and Frenchay Activities Index ( FAI ) score , all registered three years post stroke . Results : The percentages of patients still living at home after one and three years were 88 % and 83 % , respectively . Twenty per cent of the patients had deteriorated according to the BI after three years , mostly due to recurrent strokes ( odds ratio ( OR ) 10.3 ; 95 % con”dence interval ( CI ) 3.0–35.5 ) and co-morbidity with other disabling disorders ( OR 3.9 ; CI 1.1–13.5 ) . Co-morbidity also emerged as an important risk factor for dependency according to BI score ( OR 8.8 ; CI 2.4–32.1 ) as well as for a poor FAI score ( OR 4.9 ; CI 1.9–13.0 ) . BI in the early phase was the strongest predictor for long-term functional outcome . Urinary incontinence emerged as a risk factor for nursing home placement after three years ( OR 3.2 ; CI 0.9–11.3 ) . Cognitive dysfunction was a risk factor for poor FAI scoring ( OR 2.7 ; CI 1.0–7.0 ) . Conclusions : After stroke rehabilitation , concomitant chronic disabling disorders and recurrent strokes seem to play an important role regarding dependency , h and icap and long-term functional decline The third most common stroke complication is infection . We studied the rates of aspiration pneumonia and urinary tract infection ( UTI ) , their risk factors and their effect on outcome in the 1455 Glycine Antagonist ( Gavestinel ) in Neuroprotection ( GAIN ) International patients with ischaemic stroke . Forward stepwise logistic regression and Cox proportional hazards modelling identified baseline factors that predicted events and the independent effect of events up to day 7 on poor stroke outcome at 3 months in patients alive at day 7 , after correcting for prognostic factors . Higher baseline National Institute of Health Stroke Scale ( NIHSS ) and age , male gender , history of diabetes and stroke subtype predicted pneumonia , which occurred in 13.6 % of patients . Female gender and higher baseline NIHSS and age predicted UTI , which occurred in 17.2 % of patients . Pneumonia was associated with poor outcome by mortality ( hazard ratio , 2.2 ; 95 % confidence interval , 1.5 - 3.3 ) , Barthel index ( < 60 ) ( odds ratio , 3.8 ; 2.2 - 6.7 ) , NIHSS ( 4.9 ; 1.7 - 14 ) and Rankin scale ( > /=2 ) ( 3.4 ; 1.4 - 8.3 ) . UTI was associated with Barthel index ( 1.9 ; 1.2 - 2.9 ) , NIHSS ( 2.2 ; 1.2 - 4.0 ) and Rankin scale ( 3.1 ; 1.6 - 4.9 ) . Pneumonia and UTI are independently associated with stroke poor outcome . Patients with identified risk factors must be closely monitored for infection Background and Purpose — Intracerebral hemorrhage ( ICH ) is the most fatal and disabling stroke subtype . Widely used tools for prediction of mortality are fundamentally limited in that they do not account for effects of withdrawal of care and are not design ed to predict functional recovery . We developed an acute clinical score to predict likelihood of functional independence . Methods — We prospect ively characterized 629 consecutive patients with ICH at hospital presentation . Predictors of functional independence ( Glasgow Outcome Score ≥4 ) at 90 days were used to develop a logistic regression-based risk stratification scale in a r and om subset of two thirds and vali date d in the remaining one third of the cohort . Results — At 90 days , 162 ( 26 % ) patients achieved independence . Age , Glasgow Coma Scale , ICH location , volume ( all P<0.0001 ) , and pre-ICH cognitive impairment ( P=0.005 ) were independently associated with Glasgow Outcome Score ≥4 . The FUNC score was developed as a sum of individual points ( 0–11 ) based on strength of association with outcome . In both the development and validation cohorts , the proportion of patients who achieved Glasgow Outcome Score ≥4 increased steadily with FUNC score . No patient assigned a FUNC score ≤4 achieved functional independence , whereas > 80 % with a score of 11 did . The predictive accuracy of the FUNC score remained unchanged when restricted to ICH survivors only , consistent with absence of confounding by early withdrawal of care . Conclusions — FUNC score is a valid clinical assessment tool that identifies patients with ICH who will attain functional independence and thus , can provide guidance in clinical decision-making and patient selection for clinical trials Background and Purpose — Several factors predict functional status after stroke , but most studies have included hospitalized patients with limited follow-up . We hypothesized that patients with ischemic stroke experience functional decline over 5 years independent of recurrent stroke and other risk factors . Methods — In the population -based Northern Manhattan Study , patients ≥40 years of age with incident ischemic stroke were prospect ively followed using the Barthel Index at 6 months and annually to 5 years . Baseline stroke severity was categorized as mild ( National Institutes of Health Stroke Scale < 6 ) , moderate ( 6 to 13 ) , and severe ( ≥14 ) . Follow-up was censored at death , recurrent stroke , or myocardial infa rct ion . Generalized Estimating Equations provided ORs and 95 % CIs for predictors of favorable ( Barthel Index ≥95 ) versus unfavorable ( Barthel Index < 95 ) functional status after adjusting for demographic and medical risk factors . Results — Of 525 patients , mean age was 68.6±12.4 years , 45.5 % were male , 54.7 % Hispanic , 54.7 % had Medicaid/no insurance , and 35.1 % had moderate stroke . The proportion with Barthel Index ≥95 declined over time ( OR , 0.91 ; 95 % CI , 0.84 to 0.99 ) . Changes in Barthel Index by insurance status were confirmed by a significant interaction term ( & bgr ; for interaction=−0.167 , P=0.034 ) ; those with Medicaid/no insurance declined ( OR , 0.84 ; P=0.003 ) , whereas those with Medicare/private insurance did not ( OR , 0.99 ; P=0.92 ) . Conclusions — The proportion of patients with functional independence after stroke declines annually for up to 5 years , and these effects are greatest for those with Medicaid or no health insurance . This decline is independent of age , stroke severity , and other predictors of functional decline and occurs even among those without recurrent stroke or myocardial infa rct ion Objective : To compare the baseline National Institutes of Health Stroke Scale ( NIHSS ) score and the Trial of Org 10172 in Acute Stroke Treatment ( TOAST ) stroke subtype as predictors of outcomes at 7 days and 3 months after ischemic stroke . Methods : Using data collected from 1,281 patients enrolled in a clinical trial , subtype of stroke was categorized using the TOAST classification , and neurologic impairment at baseline was quantified using the NIHSS . Outcomes were assessed at 7 days and 3 months using the Barthel Index ( BI ) and the Glasgow Outcome Scale ( GOS ) . An outcome was rated as excellent if the GOS score was 1 and the BI was 19 or 20 ( scale of 0 to 20 ) . Analyses were adjusted for age , sex , race , and history of previous stroke . Results : The baseline NIHSS score strongly predicted outcome , with one additional point on the NIHSS decreasing the likelihood of excellent outcomes at 7 days by 24 % and at 3 months by 17 % . At 3 months , excellent outcomes were noted in 46 % of patients with NIHSS scores of 7 to 10 and in 23 % of patients with scores of 11 to 15 . After multivariate adjustment , lacunar stroke had an odds ratio of 3.1 ( 95 % CI , 1.5 to 6.4 ) for an excellent outcome at 3 months . Conclusions : The NIHSS score strongly predicts the likelihood of a patient ’s recovery after stroke . A score of ≥16 forecasts a high probability of death or severe disability whereas a score of ≤6 forecasts a good recovery . Only the TOAST subtype of lacunar stroke predicts outcomes independent of the NIHSS score OBJECTIVES To investigate the prognostic effect of poststroke urinary incontinence ( UI ) on 1-year outcome in relation to measurements of attention and mental processing speed . DESIGN Prospect i ve observational study . SETTING Geriatric department ( stroke and rehabilitation unit ) in a university hospital . PARTICIPANTS Two hundred thirty-five previously continent patients ( median age 78 ) with an acute stroke . MEASUREMENTS Clinical stroke syndromes , subtypes of UI , pre- and poststroke cognitive function and activities of daily living , computerized assessment of attention and processing speed for 110 of the participants , mortality and accommodation at 1 year . RESULTS One hundred seventy patients remained continent , and 65 developed UI ( 27 with urge UI , 38 with UI with impaired awareness of the need to void ( IA-UI ) . Patients with urge UI had poorer power of attention and speed of memory than continent patients but similar continuity of attention ( P<.001 , .001 , and .07 , respectively ) . Patients with IA-UI performed poorer in all categories than continent and patients with urge UI ( all P<.01 ) . In regression analyses , IA-UI was the strongest predictor of mortality and nursing home residence after 1 year ( odds ratio=15.7 , 95 % confidence interval=3.6 - 69.7 ) . When deaths were excluded , IA-UI and continuity of attention remained independent risk factors . CONCLUSION Patients with poststroke UI are less attentive than continent patients . Those with IA-UI perform poorest . Sustained attention seems important for outcome and should be taken more into account in the rehabilitation process . In patients who recognize their incontinence , attention-focused training might be the most effective measure of reestablishing bladder control We describe the incidence and natural history of four clinical ly identifiable subgroups of cerebral infa rct ion in a community-based study of 675 patients with first-ever stroke . Of 543 patients with a cerebral infa rct , 92 ( 17 % ) had large anterior circulation infa rcts with both cortical and subcortical involvement ( total anterior circulation infa rcts , TACI ) ; 185 ( 34 % ) had more restricted and predominantly cortical infa rcts ( partial anterior circulation infa rcts , PACI ) ; 129 ( 24 % ) had infa rcts clearly associated with the vertebrobasilar arterial territory ( posterior circulation infa rcts , POCI ) ; and 137 ( 25 % ) had infa rcts confined to the territory of the deep perforating arteries ( lacunar infa rcts , LACI ) . There were striking differences in natural history between the groups . The TACI group had a negligible chance of good functional outcome and mortality was high . More than twice as many deaths were due to the complications of immobility than to direct neurological sequelae of the infa rct . Patients in the PACI group were much more likely to have an early recurrent stroke than were patients in other groups . Those in the POCI group were at greater risk of a recurrent stroke later in the first year after the index event but had the best chance of a good functional outcome . Despite the small anatomical size of the infa rcts in the LACI group , many patients remained substantially h and icapped . The findings have important implication s for the planning of stroke treatment trials and suggest that various therapies could be directed specifically at the subgroups The aims of this study were : ( 1 ) to identify reliable prognostic factors for detecting subgroups of no , low and high response in consecutive patients admitted for rehabilitation of first stroke sequelae , and ( 2 ) to quantify the relative risk of poor or excellent prognosis on both Activities of Daily Living ( ADL ) and mobility for each significant variable . We prospect ively studied 440 of 475 patients . From a group of 32 independent variables , those significantly associated with no , low and high effectiveness on both ADL and mobility were selected by means of multiple regression ; then , the relative risk was calculated for each variable that significantly entered the multiple regressions . Patients with severe impairment or with global aphasia showed a relative risk of no response 4–6 times higher than that of other patients . An interval before rehabilitation longer than 2 months was associated with an increasing risk of no response . Elderly patients had a significantly higher relative risk of low response both on ADL and mobility . The presence of hemineglect and depression was associated with an increasing risk of low response on ADL but not on mobility . The absence of hemineglect and a short interval are prerequisites for an excellent functional prognosis on both ADL and mobility . A minor impairment , employed status , the absence of global aphasia and age ≤65 years increased the risk of high response . At the beginning of treatment , clear prognostic factors for the detection of subgroups with poor or excellent rehabilitation prognosis can be identified PURPOSE Early identification of predictive factors relevant to the utilization of long-term care institution for stroke patients is important and thus investigated in this study on stroke patients receiving rehabilitation therapy . METHODS This prospect i ve follow-up investigation carried out during patients ' clinical visits , at homes or long-term care institutions , was conducted at least 6 months after stroke on 151 stroke survivors . Functional ability was evaluated with the functional independence measure ( FIM ) instrument at discharge of the inpatient rehabilitation programme . Balance status was measured using the seven item balance scale of the Fugl-Meyer sensorimotor assessment ( FMSA ) . Major medical , rehabilitative and sociodemographic factors were also examined during hospitalization period as independent variables . RESULTS Of all the patients surveyed , 23 ( 15.2 % ) had been living in long-term care institutions . Univariate statistical analysis indicated that the significant factors related to long-term care institution utilization included recurrence of attack , bilateral involvement , impaired orientation , and functional and balance status at discharge . CONCLUSIONS Basing on the significant predictors identified , analysis using the logistic regression model correctly classified three quarters of the subjects as long-term care institution residents . The strongest predictors of long-term care institution utilization for stroke patients following rehabilitation therapy were : bilaterally affected , impaired orientation and poor st and ing ability at discharge BACKGROUND AND PURPOSE Hypertension is the most important modifiable risk factor for secondary stroke prevention but the immediate management of blood pressure after stroke is uncertain . We evaluated outcomes in the NINDS tPA stroke study in relation to blood pressure declines during the first 24 h after r and omization . METHODS Declines in blood pressure compared to baseline and preceding time points were analyzed in relationship to favorable outcomes ( by a global test ) , poor outcomes ( Rankin scale > 3 ) and death at 3 months . RESULTS 551 patients did not receive immediate pre-r and omization anti-hypertensive treatment and had available blood pressures . Multivariate analysis showed significantly and progressively reducing likelihoods of a favorable outcome with each 10 mmHg decline in systolic blood pressure ( SBP ) > 50 mmHg compared to any preceding measurement . Poor outcomes were significantly more likely in patients with > 50 mmHg SBP reduction ( or > 30 mmHg compared to any immediately preceding measurement ) . There was an increased risk of death with blood pressure declines > 60 mmHg . tPA treatment still produced favorable outcomes compared with placebo even with blood pressure declines . The median largest SBP reduction from baseline in patients treated with tPA was 35 mmHg compared to 30 mmHg in placebo-treated patients ( p<0.01 ) . CONCLUSIONS In this post hoc analysis , progressively reducing likelihoods of a favorable outcome were seen with increasing declines in SBP . Despite a greater likelihood of favorable outcomes , tPA treatment was associated with a greater reduction in blood pressure than placebo . R and omized trials of blood pressure management are needed Background and purpose : Pre-existing cognitive decline and new-onset dementia are common in patients with stroke , but their influence on institutionalisation rates is unknown . Objective : To evaluate the influence of cognitive impairment on the institutionalisation rate 3 years after a stroke . Design : ( 1 ) The previous cognitive state of 192 consecutive patients with stroke living at home before the stroke ( with the Informant Question naire on COgnitive Decline in the Elderly ( IQCODE ) ) , ( 2 ) new-onset dementia occurring within 3 years and ( 3 ) institutionalisation rates within 3 years in the 165 patients who were discharged alive after the acute stage were prospect ively evaluated . Results : Independent predictors of institutionalisation over a 3-year period that were available at admission were age ( adjusted odds ratio ( adjOR ) for 1-year increase = 1.08 ; 95 % confidence interval ( CI ) 1.03 to 1.15 ) , severity of the neurological deficit ( adjOR for 1-point increase in Orgogozo score = 0.97 ; 95 % CI 0.96 to 0.99 ) and severity of cognitive impairment ( adjOR for 1-point increase in IQCODE score = 1.03 ; 95 % CI 1 to 1.06 ) . Factors associated with institutionalisation at 3 years that were present at admission or occurred during the follow-up were age ( adjOR for 1-year increase = 1.17 ; 95 % CI 1.07 to 1.27 ) and any ( pre-existing or new ) dementia ( adjOR = 5.85 ; 95 % CI 1.59 to 21.59 ) , but not the severity of the deficit of the neurological deficit . Conclusion : Age and cognitive impairment are more important predictors of institutionalisation 3 years after a stroke than the severity of the physical disability OBJECTIVE To evaluate the outcome of stroke stratified according to both initial stroke severity and initial level of disability . DESIGN Prospect i ve , consecutive , and community based . SETTING A stroke unit of a hospital in Denmark . This setting receives all acute stroke patients admitted from a well-defined catchment area of 239,886 inhabitants within the City of Copenhagen . Acute treatment as well as all stages of rehabilitation are cared for within the stroke unit regardless of age , stroke severity , and premorbid condition . PATIENTS 1197 patients with acute stroke . MAIN OUTCOME MEASURES Primary outcome was measured as death , discharge to nursing home , or to own home . Secondary outcome was measured as neurological deficits and functional disabilities after completed rehabilitation and again 6 months after stroke onset , using the Sc and inavian Neurological Stroke Scale and the Barthel Index . RESULTS Stroke was initially very severe in 223 ( 19 % ) of the patients , severe in 171 ( 14 % ) , moderate in 316 ( 26 % ) , and mild in 487 ( 41 % ) patients . Two hundred and fifty ( 21 % ) patients died during hospital stay , 177 ( 15 % ) were discharged to nursing home , and 770 ( 64 % ) patients were discharged to their own home . After completed rehabilitation , 11 % of survivors still had severe or very severe neurological deficits , 11 % had moderate deficits , and 78 % had no or only mild deficits ; 20 % were severely or very severely disabled , 8 % were moderately disabled , 26 % were mildly disabled , and 46 % had no disability in activities of daily living . Detailed information on outcome stratified according to initial stroke severity/disability also is presented . CONCLUSIONS This study provides a thorough description of the needs for stroke rehabilitation in the community and the amount of postrehabilitation disability in stroke survivors . For outcome prediction , the results can be used as a reliable tool for prognostication of the chances ( or risks ) of various outcomes in patients characterized by initial degree of stroke severity and /or functional disability using simple , reliable scores in the acute phase of stroke . However , the results should not be used as a guideline for selecting patients for rehabilitation in the acute phase because even the most severe cases regularly experience meaningful improvement during rehabilitation Purpose : To identify predictors of outcome after 12 months in elderly stroke patients rehabilitated in a geriatric ward . Design : Prospect i ve with evaluation in the subacute phase and after 12 months . Setting : Geriatric ward and outpatient clinic . Subjects : All stroke patients admitted from the acute unit to a geriatric ward for rehabilitation during a 16-month period ( n = 171 ) . Main outcome measures : Place of living , mortality and social functioning ( Frenchay Activities Index ) 12 months following stroke . Results : Age , urinary incontinence and cognitive function were significantly associated with place of living ( home versus nursing home ) 12 months post stroke in bivariate analyses . However , using multivariate logistic regression analyses , only age ( p = 0.005 ) and urinary incontinence at baseline ( p = 0.028 ) remained independent predictors of place of living . Mortality during the first year was significantly predicted by urinary incontinence and gender ( men doing worse ) , whereas the Barthel Activities of Daily Living ( ADL ) Index sumscore was the only significant independent predictor of social activities . Conclusion : Urinary incontinence at baseline seems to be a most important predictor of outcome 12 months post stroke in geriatric patients . However , with regard to social activities ( Frenchay Activities Index ) , functional impairment in the initial phase as reflected by the Barthel ADL Index supersedes other predictors OBJECTIVES To investigate the prevalence , incidence , clinical types , and prognostic effect of micturition disturbances in acute stroke . DESIGN Prospect i ve observational study . SETTING Geriatric department ( stroke and rehabilitation unit ) in a community hospital ( acute phase ) ; outpatient clinic , patients ' own homes , or nursing homes ( 3 months follow-up ) . PARTICIPANTS Three hundred fifteen patients ( mean age 77 ) with acute first-ever or recurrent stroke consecutively admitted to the hospital stroke unit . MEASUREMENTS Premorbid basic and instrumental activities of daily living ( ADLs ) and mental functioning ; comorbidity ; previous and actual micturition symptoms ; stroke syndromes ; medication use ; and poststroke mobility , ADLs , and cognition . RESULTS One hundred forty-seven patients ( 46 % ) had preexisting micturition disturbances ( urinary incontinence ( UI ) , n = 98 ; urgency/frequency , n = 37 ; voiding difficulties , n = 12 ) . Seventy-eight developed new symptoms ( UI , n = 65 ; urgency/frequency , n = 4 ; sustained retention , n = 9 ) . There were two UI types : urge UI ( n = 27 ) and UI with impaired awareness of bladder needs ( IA UI , n = 38 ) . In regression analyses , IA UI was the only micturition disturbance predicting mortality and need for nursing home care at 3 months ( odds ratio ( OR ) = 27.5 , 95 % confidence interval ( CI ) = 7.0 - 108.2 ) , together with poor mobility ( OR = 8.2 , 95 % CI = 2.6 - 26.2 ) , and partial or total anterior circulation stroke type ( OR = 3.6 , 95 % CI = 1.4 - 9.0 ) . CONCLUSION New-onset poststroke UI with impaired awareness of bladder needs is a strong and independent risk factor for poor outcome at 3 months . This probably reflects more serious brain damage , affecting sustained attention and information processing . Valid clinical tools to detect such dysfunction in stroke victims are needed . Clinical classification of poststroke UI is likely to improve management BACKGROUND AND PURPOSE Blood pressure is elevated in most patients during acute ischemic stroke , but the prognostic significance of this is unclear as the current data yield conflicting results . METHODS Admission blood pressure from the 1281 patients in the Trial of ORG 10172 in Acute Stroke Treatment ( TOAST ) was analyzed for prognostic significance as well as the risk of hemorrhagic transformation . We also examined weighted-average blood pressure over seven days , and the impact of a 30 % change in blood pressure in 24 hours . Patients with severe hypertension were excluded from the TOAST trial . RESULTS Increasing systolic blood pressure ( SBP ) on admission , but not diastolic ( DBP ) or mean arterial pressure ( MAP ) was predictive of poor outcome , but this effect was not significant after adjustment for other know prognostic factors . Increasing weighted-average SBP and MAP over seven days were predictive for poor outcome , but a 30 % change in blood pressure over 24 hours was not . CONCLUSIONS Admission blood pressure is not an independent prognostic factor in acute ischemic stroke , but the weighted-average of SBP and MAP over seven days probably does have predictive value with higher values having a worse prognosis . A prospect i ve trial of blood pressure control during acute stroke is needed |
13,847 | 27,276,077 | DISCUSSION / CONCLUSIONS Use of calcium results in higher mortality than either sevelamer in particular and NCBPBs in general ( moderate quality evidence ) .
Our results raise questions about whether administration of calcium as an intervention for CKD- MBD remains ethical . | BACKGROUND Chronic kidney disease-mineral and bone disorder ( CKD-MBD ) has been linked to poor health outcomes , including diminished quality and length of life .
This condition is characterized by high phosphate levels and requires phosphate-lowering agents-phosphate binders .
The objective of this systematic review is to compare the effects of available phosphate binders on patient-important outcomes in patients with CKD-MBD . | BACKGROUND Lanthanum carbonate ( LC ) , an effective non-calcium phosphate binder is widely used to manage hyperphosphatemia in patients with chronic kidney disease ( CKD ) on dialysis . Recently , the additional indication for control of hyperphosphatemia in CKD patients not on dialysis has been approved . METHODS A multicenter , r and omized , double-blind , placebo-controlled trial to confirm the efficacy and safety of LC in Japanese hyperphosphatemic stage 4 - 5 CKD patients not on dialysis . After a 4-week run-in period , 143 eligible subjects with serum phosphate levels of 5.6 - 11.0 mg/dL were r and omized ( 2 : 1 ) to receive LC or placebo ( 88 vs. 55 ) for 8 weeks ; 119 subjects completed the study ( 76 vs. 43 ) . The starting LC dose was 750 mg/day , which was then up-titrated to 2,250 mg/day as needed while tolerated . Primary efficacy analysis was performed on the intent-to-treat ( ITT ) population of 141 patients ( 86 vs. 55 ) . RESULTS LC produced a significantly greater reduction in serum phosphate level compared with placebo after 8 weeks of treatment ( difference , 0.97 ( 95 % CI : 0.58 , 1.37 ) mg/ dL ; p < 0.0001 ) . The cumulative proportion of subjects with controlled phosphate levels ≤ 4.6 mg/dL was higher in the LC group than the placebo group ( 59.56 % vs. 10.46 % ) . LC caused significantly greater reductions in serum Ca × P product and urinary phosphate excretion compared with placebo . The safety profile of LC was similar to that of placebo . CONCLUSIONS This study demonstrated the effectiveness of LC to control hyperphosphatemia in pre-dialysis CKD patients BACKGROUND JTT-751 is a novel phosphate binder containing ferric citrate as the active ingredient . METHODS In this Phase 3 , multicenter , r and omized , open-label , parallel-group study , we compared the efficacy and safety of JTT-751 and sevelamer hydrochloride in patients undergoing hemodialysis . A total of 230 patients with a serum phosphate ≥1.97 and < 3.23 mmol/L were r and omized to JTT-751 ( dose adjusted between 1.5 and 6.0 g/day ) or sevelamer hydrochloride ( dose adjusted between 3.0 and 9.0 g/day ) for 12 weeks . The primary outcome was change in serum phosphate from baseline to end of treatment . Secondary outcomes included the changes in corrected serum calcium and intact parathyroid hormone ( PTH ) . The changes in ferritin , transferrin saturation and erythropoiesis-stimulating agent dose were additional outcomes . RESULTS Changes in serum phosphate at the end of treatment were -0.82 mmol/L in the JTT-751 group and -0.78 mmol/L in the sevelamer group , establishing non-inferiority of JTT-751 compared with sevelamer ( least squares mean , -0.03 mmol/L ; 95 % confidence interval , -0.13 to 0.07 mmol/L ) . Corrected serum calcium increased and PTH decreased from baseline within both groups ; changes between groups were similar . Gastrointestinal disorders were the most common adverse events in both groups ; the incidence of diarrhea was higher in the JTT-751 group , while constipation occurred frequently in the sevelamer group . Treatment with JTT-751 result ed in significant relative increases in serum ferritin and transferrin saturation . CONCLUSIONS Efficacy and safety of JTT-751 was comparable to sevelamer in patients on hemodialysis with hyperphosphatemia . Differential adverse effects were observed ; biochemical markers of iron status increased in patients treated with JTT-751 . TRIAL REGISTRATION NUMBER CTI-111433 ( The Japan Pharmaceutical Information Center at : http//www . clinical trials.jp ) . Date of registration : 7 March 2011 Background and Aims : Calcium-containing phosphate binders have been shown to increase the progression of vascular calcification in hemodialysis patients . This is a prospect i ve study that compares the effects of calcium acetate and sevelamer on coronary calcification ( CAC ) and bone histology . Methods : 101 hemodialysis patients were r and omized for each phosphate binder and su bmi tted to multislice coronary tomographies and bone biopsies at entry and 12 months . Results : The 71 patients who concluded the study had similar baseline characteristics . On follow-up , the sevelamer group had higher levels of intact parathyroid hormone ( 498 ± 352 vs. 326 ± 236 pg/ml , p = 0.017 ) , bone alkaline phosphatase ( 38 ± 24 vs. 28 ± 15 U/l , p = 0.03 ) and deoxypyridinoline ( 135 ± 107 vs. 89 ± 71 nmol/l , p = 0.03 ) and lower LDL cholesterol ( 74 ± 21 vs. 91 ± 28 mg/dl , p = 0.015 ) . Phosphorus ( 5.8 ± 1.0 vs. 6 ± 1.0 mg/dl , p = 0.47 ) and calcium ( 1.27 ± 0.07 vs. 1.23 ± 0.08 mmol/l , p = 0.68 ) levels did not differ between groups . CAC progression ( 35 vs. 24 % , p = 0.94 ) and bone histological diagnosis at baseline and 12 months were similar in both groups . Patients of the sevelamer group with a high turnover at baseline had an increase in bone resorption ( eroded surface , ES/BS = 9.0 ± 5.9 vs. 13.1 ± 9.5 % , p = 0.05 ) , whereas patients of both groups with low turnover at baseline had an improvement in bone formation rate ( BFR/BS = 0.015 ± 0.016 vs. 0.062 ± 0.078 , p = 0.003 for calcium and 0.017 ± 0.016 vs. 0.071 ± 0.084 μm3/μm2/day , p = 0.010 for sevelamer ) . Conclusions : There was no difference in CAC progression or changes in bone remodeling between the calcium and the sevelamer groups Background High levels of circulating fibroblast growth factor 23 ( FGF23 ) are associated with chronic kidney disease ( CKD ) progression and high mortality . In the Phosphate Reduction Evaluation of FGF23 in Early CKD Treatment ( PREFECT ) study , we assessed the effect of reducing intestinal phosphate absorption using lanthanum carbonate on FGF23 levels in normophosphatemic patients with CKD stage 3 . Methods Thirty-five individuals were r and omized to lanthanum carbonate 3000 mg/day ( n = 23 ) or placebo ( n = 12 ) for 12 weeks . Levels of intact FGF23 ( iFGF23 ) , C-terminal FGF23 , serum and urinary phosphate and calcium , intact parathyroid hormone and 1,25-dihydroxyvitamin D were assessed . Results The median age was 65 years in the lanthanum group and 73 years in the placebo group ; 58.8 % and 41.7 % were men , respectively . No significant difference was seen in mean iFGF23 between groups at week 12 . There was , however , a transient reduction from baseline in iFGF23 in the lanthanum group at week 1 , from 70.5 pg/ml to 51.9 pg/ml , which was not seen in the placebo group ; this between-group difference in percentage change from baseline was significant in post hoc analyses ( p = 0.0102 ) . Urinary phosphate decreased after 1 week of lanthanum treatment and remained low at week 12 . Conclusions Reducing intestinal phosphate absorption with lanthanum carbonate did not lead to sustained reductions in iFGF23 in patients with CKD stage 3 , although phosphaturia decreased . This suggests that factors other than phosphate burden may be responsible for driving increases in circulating FGF23 in patients with CKD.Trial registration Clinical Trials.gov NCT01128179 , 20 May 2010 BACKGROUND Iron deficiency anemia and serum phosphate levels > 4.0mg/dL are relatively common in chronic kidney disease stages 3 to 5 and are associated with higher risks of progressive loss of kidney function , cardiovascular events , and mortality . STUDY DESIGN Double-blind , placebo-controlled , r and omized trial . SETTING & PARTICIPANTS 149 patients with estimated glomerular filtration rates < 60 mL/min/1.73 m(2 ) , iron deficiency anemia ( hemoglobin , 9.0 - 12.0 g/dL ; transferrin saturation [TSAT]≤ 30 % , serum ferritin ≤ 300 ng/mL ) , and serum phosphate levels ≥ 4.0 to 6.0mg/dL. Use of intravenous iron or erythropoiesis-stimulating agents was prohibited . INTERVENTION R and omization to treatment for 12 weeks with ferric citrate coordination complex ( ferric citrate ) or placebo . OUTCOMES & MEASUREMENTS Co primary end points were change in TSAT and serum phosphate level from baseline to end of study . Secondary outcomes included change from baseline to end of treatment in values for ferritin , hemoglobin , intact fibroblast growth factor 23 ( FGF-23 ) , urinary phosphate excretion , and estimated glomerular filtration rate . RESULTS Ferric citrate treatment increased mean TSAT from 22 % ± 7 % ( SD ) to 32 % ± 14 % and reduced serum phosphate levels from 4.5 ± 0.6 to 3.9 ± 0.6 mg/dL , while placebo exerted no effect on TSAT ( 21 % ± 8 % to 20 % ± 8 % ) and less effect on serum phosphate level ( 4.7 ± 0.6 to 4.4 ± 0.8 mg/dL ; between-group P<0.001 for each ) . Ferric citrate increased hemoglobin levels ( from 10.5 ± 0.8 to 11.0 ± 1.0 g/dL ; P<0.001 vs placebo ) , reduced urinary phosphate excretion 39 % ( P<0.001 vs placebo ) , and reduced serum intact FGF-23 levels from a median of 159 ( IQR , 102 - 289 ) to 105 ( IQR , 65 - 187 ) pg/mL ( P=0.02 vs placebo ) . The incidence and severity of adverse effects were similar between treatment arms . LIMITATIONS The study is limited by relatively small sample size and short duration and by having biochemical rather than clinical outcomes . CONCLUSIONS Short-term use of ferric citrate repletes iron stores , increases hemoglobin levels , and reduces levels of serum phosphate , urinary phosphate excretion , and FGF-23 in patients with chronic kidney disease stages 3 to 5 BACKGROUND AND OBJECTIVES Ferric citrate hydrate is a novel iron-based phosphate binder being developed for hyperphosphatemia in patients with CKD . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS A phase 3 , multicenter , r and omized , double blind , placebo-controlled study investigated the efficacy and safety of ferric citrate hydrate in nondialysis-dependent patients with CKD . Starting in April of 2011 , 90 CKD patients ( eGFR=9.21±5.72 ml/min per 1.73 m(2 ) ) with a serum phosphate≥5.0 mg/dl were r and omized 2:1 to ferric citrate hydrate or placebo for 12 weeks . The primary end point was change in serum phosphate from baseline to the end of treatment . Secondary end points included the percentage of patients achieving target serum phosphate levels ( 2.5 - 4.5 mg/dl ) and change in fibroblast growth factor-23 at the end of treatment . RESULTS The mean change in serum phosphate was -1.29 mg/dl ( 95 % confidence interval , -1.63 to -0.96 mg/dl ) in the ferric citrate hydrate group and 0.06 mg/dl ( 95 % confidence interval , -0.20 to 0.31 mg/dl ) in the placebo group ( P<0.001 for difference between groups ) . The percentage of patients achieving target serum phosphate levels was 64.9 % in the ferric citrate hydrate group and 6.9 % in the placebo group ( P<0.001 ) . Fibroblast growth factor-23 concentrations were significantly lower in patients treated with ferric citrate hydrate versus placebo ( change from baseline [ median ] , -142.0 versus 67.0 pg/ml ; P<0.001 ) . Ferric citrate hydrate significantly increased serum iron , ferritin , and transferrin saturation compared with placebo ( P=0.001 or P<0.001 ) . Five patients discontinued active treatment because of treatment-emergent adverse events with ferric citrate hydrate treatment versus one patient with placebo . Overall , adverse drug reactions were similar in patients receiving ferric citrate hydrate or placebo , with gastrointestinal disorders occurring in 30.0 % of ferric citrate hydrate patients and 26.7 % of patients receiving placebo . CONCLUSION In patients with nondialysis-dependent CKD , 12-week treatment with ferric citrate hydrate result ed in significant reductions in serum phosphate and fibroblast growth factor-23 while simultaneously increasing serum iron parameters BACKGROUND Sevelamer hydrochloride was recently proposed as a phosphate binder to prevent hypercalcaemia in place of calcium alkaline salts in dialysis patients . So far , it has been evaluated only in patients receiving calcitriol , without comparison with CaCO(3 ) alone , although the latter was found to be as effective as the combination of calcitriol and Al(OH)(3 ) in suppressing parathyroid hormone ( PTH ) without inducing hypercalcaemia and to have a better lowering effect on serum phosphate . Moreover , this bile salt binder may decrease serum 25-OH vitamin D. Therefore , we compared for 5 months two strategies for controlling moderate hyperparathyroidism : CaCO(3 ) alone vs sevelamer in conjunction with measures to increase calcium balance . METHODS Forty-two patients were r and omized : 21 continued their treatment with 4.8 g/day CaCO(3 ) and 21 were switched to sevelamer ( initial dose : 2.4 g/day , increased to 4.4 g/day ) . Each month , when serum-corrected calcium decreased below 2.30 mmol/l , dialysate calcium was increased or alphacalcidol was given at each dialysis session , according to serum PO(4 ) levels . The following parameters were monitored : serum Ca , PO(4 ) , bicarbonate and protein , weekly ; and serum PTH , 25-OH vitamin D and total , LDL and HDL cholesterol monthly . RESULTS Except for higher serum phosphate at month 1 , lower serum bicarbonate at month 2 and lower LDL cholesterol at month 5 in the sevelamer group , no difference was found between the two groups . Compared with baseline levels , PTH increased and 25-OH vitamin D decreased significantly in both groups , these two parameters being inversely correlated . CONCLUSIONS Given comparable control of plasma calcium , phosphate and 25-OH vitamin D , PTH control is comparable in both strategies . Sevelamer does not induce greater vitamin D depletion than CaCO(3 ) . The transient decrease of serum bicarbonate after discontinuation of CaCO(3 ) in the sevelamer group suggests a less optimal prevention of acidosis . The sevelamer-induced decrease in LDL cholesterol gives this drug a potential advantage in cardiovascular prevention Vascular calcification ( VC ) contributes to cardiovascular disease in hemodialysis ( HD ) patients , especially with diabetes mellitus ( DM ) complications . No r and omized studies have been published regarding the effect of lanthanum carbonate ( LC ) on VC progression in DM patients . The aim of this study was to evaluate the effects of lanthanum carbonate on the progression of VC in HD patients with type 2 DM . We conducted a r and omized controlled trial comparing LC with calcium carbonate ( CC ) in 43 HD patients at a single dialysis center . Estimations of aortic calcification index ( ACI ) by abdominal computed tomography were performed twice for each patient ( at baseline and 12 months ) . Forty-one patients completed the study ( 19 LC , 22 CC ) . When ACI at baseline was ≦0.48 ( median of baseline ACI ) , median change in ACI ( Δ%ACI ) was 20.44 ( 11.50 - 36.80 % ) in the LC group , and 40.00 ( 33.30 - 92.60 % ) in the CC group ( P = 0.026 ) . On the other h and , when ACI at baseline was > 0.48 , the median change in ACI ( Δ%ACI ) was 6.42 ( 3.13 - 24.40 % ) in the LC group , and 8.08 ( 5.68 - 12.20 % ) in the CC group ( P = 1.000 ) . Serum markers of chronic kidney disease-mineral and bone disorder ( CKD-MBD ) , HbA1c , dose of vitamin D analogues , and side-effects of medications did not change in either group throughout the study except int-PTH increased in the LC group . This study indicated that administration of LC inhibited the progression of VC in patients receiving HD for type 2 DM , only in cases of slight VC compared with CC In the GRADE approach , r and omized trials start as high- quality evidence and observational studies as low- quality evidence , but both can be rated down if a body of evidence is associated with a high risk of publication bias . Even when individual studies included in best- evidence summaries have a low risk of bias , publication bias can result in substantial overestimates of effect . Authors should suspect publication bias when available evidence comes from a number of small studies , most of which have been commercially funded . A number of approaches based on examination of the pattern of data are available to help assess publication bias . The most popular of these is the funnel plot ; all , however , have substantial limitations . Publication bias is likely frequent , and caution in the face of early results , particularly with small sample size and number of events , is warranted BACKGROUND Elevations in serum phosphorus are associated with renal decline in animal models and progression of established chronic kidney disease ( CKD ) in human observational studies . We examined whether serum phosphorus levels increase the risk of incident CKD or end-stage renal disease ( ESRD ) in two population -based prospect i ve cohort studies . METHODS Overall , 2269 participants free of CKD [ estimated glomerular filtration rate ( eGFR ) < 60 mL/min/1.73(2 ) ] from the Framingham Heart Study ( FHS ; mean age 42 years ; 53 % women ) and 13,372 participants from the Third National Health and Nutrition Examination Survey ( NHANES III ; mean age 44.3 years , 52 % women ) contributed to the present study . In the FHS , we evaluated the relationship between baseline phosphorus category ( < 2.5 mg/dL , 2.5 - 3.49 mg/dL , 3.5 - 3.99 mg/dL and ≥4 mg/dL ) and incident CKD ( n = 267 ) . In NHANES , we examined the relationship between phosphorus below and above 4 mg/dL in relation to incident ESRD ( n = 65 ) . RESULTS FHS participants in the highest phosphorus category had an increased risk of CKD [ odds ratio 2.14 ; 95 % confidence interval ( CI ) , 1.07 - 4.28 ; P = 0.03 ] in multivariable-adjusted models when compared to the referent group ( 2.5 - 3.49 mg/dL ) . Similarly , NHANES III participants with phosphorus levels ≥4 mg/dL demonstrated an increased risk of incident ESRD compared to those < 4 mg/dL ( relative risk 1.90 ; 95 % CI 1.03 - 3.53 ; P = 0.04 ) . CONCLUSIONS In prospect i ve studies of the general population , serum phosphorus levels in the upper-normal range were associated with a doubling in the risk of developing incident CKD and ESRD Background Coronary calcification in patients with end-stage renal disease ( ESRD ) is associated with an increased risk of cardiovascular outcomes and death from all causes . Previous evidence has been limited by short follow-up periods and inclusion of a heterogeneous cluster of events in the primary analyses . Objective To describe coronary calcification in patients incident to ESRD , and to identify whether calcification predicts vascular events or death . Design Prospect i ve sub study of an inception cohort . Setting Tertiary care haemodialysis centre in Ontario ( St Joseph ’s Healthcare Hamilton ) . Participants Patients starting haemodialysis who were new to ESRD . Measurements At baseline , clinical characterization and spiral computed tomography ( CT ) to score coronary calcification by the Agatston-Janowitz 130 scoring method . A primary outcome composite of adjudicated stroke , myocardial infa rct ion , or death . Methods We followed patients prospect ively to identify the relationship between cardiac calcification and subsequent stroke , myocardial infa rct ion , or death , using Cox regression . Results We recruited 248 patients in 3 centres to our main study , which required only biochemical markers . Of these 164 were at St Joseph ’s healthcare , and eligible to participate in the sub study ; of these , 51 completed CT scanning ( 31 % ) . Median follow up was 26 months ( Q1 , Q3 : 14 , 34 ) . The primary outcome occurred in 16 patients ; 11 in the group above the median and 5 in the group below ( p = 0.086 ) . There were 26 primary outcomes in 16 patients ; 20 ( 77 % ) events in the group above the coronary calcification median and 6 ( 23 % ) in the group below ( p = 0.006 ) . There were 10 deaths ; 8 in the group above the median compared with 2 in the group below ( p = 0.04 ) . The hazard ratios for coronary calcification above , compared with below the median , for the primary outcome composite were 2.5 ( 95 % CI 0.87 , 7.3 ; p = 0.09 ) and 1.7 ( 95 % CI 0.55 , 5.4 ; p = 0.4 ) , unadjusted and adjusted for age , respectively . For death , the hazard ratios were 4.6 ( 95 % CI 0.98 , 21.96 ; p = 0.054 ) and 2.4 ( 95 % CI 0.45 , 12.97 ; p = 0.3 ) respectively . Limitations We were limited by a small sample size and a small number of events . Conclusions Respondent burden is high for additional testing around the initiation of dialysis . High coronary calcification in patients new to ESRD has a tendency to predict cardiovascular outcomes and death , though effects are attenuated when adjusted for age . Abrégé Context eLa calcification de l'artère coronaire chez les patients atteints d’insuffisance rénale terminale ( IRT ) est associée à un risque accru de troubles cardiovasculaires et de mortalité , toutes causes confondues . Les données précédemment recueillies se limitaient à un suivi de courte durée , de même qu’à l ’ inclusion de séries d’accidents non liés lors de l’analyse préliminaire . ObjectifsDécrire la calcification de l'artère coronaire chez les patients atteints d’IRT et déterminer si la calcification de l'artère coronaire peut prédire des accidents vasculaires et la mort . Type d’étudeSous-étude prospect i ve de cohorte selon le mode d'installation . CadreUne unité de soins tertiaires en dialyse , en Ontario ( St Joseph ’s Healthcare Hamilton ) . Participants Des patients qui sont nouvellement atteints d’IRT et qui entament une hémodialyse . MesuresEn début de traitement , une caractérisation clinique et une tomodensitométrie ( TDM ) hélicoïdale qui permettent de mesurer la calcification de l'artère coronaire sur 130 , selon l’échelle d’Agatston-Janowitz . L’indicateur principal des résultats comprend l’AVC , l’infa rct us du myocarde ou la mort . MéthodesNous avons suivi les patients de manière prospect i ve , afin de cibler la relation entre la calcification de l'artère coronaire et l’AVC , l’infa rct us du myocarde ou la mort subséquente , en utilisant la régression de Cox . RésultatsNous avons recruté 248 patients dans trois unités , dans le cadre de l’étude principale , qui ne requérait que des biomarqueurs chimiques . De ces patients , 164 étaient de St Joseph ’s Healthcare , et étaient admissibles à la sous-étude ; 51 avaient effectué une tomographie par ordinateur ( 31 % ) . Le suivi médian s’étendait sur 26 mois ( Q1 , Q3 : 14 , 34 ) . L’indicateur principal a été observé chez 16 patients ; 11 dans le groupe se trouvant au-dessus de la médiane , et 5 dans le groupe inférieur ( p?=?0,086 ) . On a observé 26 indicateurs principaux chez 16 patients ; 20 ( 77 % ) accidents dans le groupe se trouvant au-dessus de la médiane en ce qui a trait à la calcification et 6 ( 23 % ) dans le groupe inférieur ( p?=?0,006 ) . Il y a eu 10 décès ; 8 dans le groupe se trouvant au-dessus de la médiane et 2 dans le groupe inférieur ( p?=?0,04 ) . Les taux de risque de calcification de l'artère coronaire se trouvant au-dessus et sous la médiane , pour les indicateurs principaux , étaient respectivement de 2,5 ( 95 % IC 0,98 ; 21,96 ; p?=?0,054 ) et 2,4 ( 95 % IC 0,45 , 12,97 ; p?=?0,3).Limites de l’étudeNous avons été limités par la taille restreinte de l’échantillon , de même que par le petit nombre d’accidents . Conclusion Le fardeau du répondant repose sur des examens supplémentaires au moment de commencer la dialyse . Un fort taux de calcification de l’artère coronaire chez les patients nouvellement atteints d’IRT tend à prédire des accidents cardiovasculaires et la mort , bien que les effets soient atténués après révision en fonction de l'âge Background . Phosphate binders are required to control serum phosphorus in dialysis patients . A phosphate binder combining calcium and magnesium offers an interesting therapeutic option . Methods . This controlled r and omized , investigator-masked , multicentre trial investigated the effect of calcium acetate/magnesium carbonate ( CaMg ) on serum phosphorus levels compared with sevelamer hydrochloride ( HCl ) . The study aim was to show non-inferiority of CaMg in lowering serum phosphorus levels into Kidney Disease Outcome Quality Initiative ( K/DOQI ) target level range after 24 weeks . Three hundred and twenty-six patients from five European countries were included . After a phosphate binder washout period , 255 patients were r and omized in a 1:1 fashion . Two hundred and four patients completed the study per protocol ( CaMg , N = 105 ; dropouts N = 18 ; sevelamer-HCl , N = 99 ; dropouts N = 34 ) . Patient baseline characteristics were similar in both groups . Results . Serum phosphorus levels had decreased significantly with both drugs at week 25 , and the study hypothesis of CaMg not being inferior to sevelamer-HCl was confirmed . The area under the curve for serum phosphorus ( P = 0.0042 ) and the number of visits above K/DOQI ( ≤1.78 mmol/L , P = 0.0198 ) and Kidney disease : Improving global outcomes ( KDIGO ) targets ( ≤1.45 mmol/L , P = 0.0067 ) were significantly lower with CaMg . Ionized serum calcium did not differ between groups ; total serum calcium increased in the CaMg group ( treatment difference 0.0477 mmol/L ; P = 0.0032 ) but was not associated with a higher risk of hypercalcaemia . An asymptomatic increase in serum magnesium occurred in CaMg-treated patients ( treatment difference 0.2597 mmol/L , P < 0.0001 ) . There was no difference in the number of patients with adverse events . Conclusion . CaMg was non-inferior to the comparator at controlling serum phosphorus levels at Week 25 . There was no change in ionized calcium ; there was minimal increase in total serum calcium and a small increase in serum magnesium . It had a good tolerability profile and thus may represent an effective treatment of hyperphosphataemia Background Serum phosphorus control is critical for chronic kidney disease ( CKD ) 5D patients . Currently , clinical profile for an oral phosphorus binder in the mainl and Chinese population is not available . Objective To establish the efficacy , safety , and tolerability of lanthanum carbonate in CKD 5D patients . Design Multicenter , r and omized , double blind , placebo-controlled study . A central r and omization center used computer generated tables to allocate treatments . Setting Twelve tertiary teaching hospitals and medical university affiliated hospitals in mainl and China . Participants Overall , 258 hemodialysis or continuous ambulatory peritoneal dialysis ( CAPD ) adult patients were enrolled . InterventionAfter a 0–3-week washout period and a 4-week lanthanum carbonate dose-titration period , 230 patients were r and omized 1:1 to receive lanthanum carbonate ( 1500 mg-3000 mg ) or placebo for a further 4-week maintenance phase . Main outcome measures Efficacy and safety of lanthanum carbonate to achieve and maintain target serum phosphorus concentrations were assessed . Results In the titration phase , serum phosphorus concentrations of all patients decreased significantly . About three-fifths achieved target levels without significantly disturbing serum calcium levels . At the end of the maintenance period , the mean difference in serum phosphorus was significantly different between the lanthanum carbonate and placebo-treated groups ( 0.63±0.62 mmol/L vs. 0.15±0.52 mmol/L , P < 0.001 ) . The drug-related adverse effects were mild and mostly gastrointestinal in nature . Conclusion Lanthanum carbonate is an efficacious and well-tolerated oral phosphate binder with a mild AE profile in hemodialysis and CAPD patients . This agent may provide an alternative for the treatment of hyperphosphatemia in CKD 5D patients in mainl and China . Trial registration No. Efficacy of PA21 ( sucroferric oxyhydroxide ) , a novel calcium-free polynuclear iron(III)-oxyhydroxide phosphate binder , was compared with that of sevelamer carbonate in an open-label , r and omized , active-controlled phase III study . Seven hundred and seven hemo- and peritoneal dialysis patients with hyperphosphatemia received PA21 1.0–3.0 g per day and 348 received sevelamer 4.8–14.4 g per day for an 8-week dose titration , followed by 4 weeks without dose change , and then 12 weeks maintenance . Serum phosphorus reductions at week 12 were −0.71 mmol/l ( PA21 ) and −0.79 mmol/l ( sevelamer ) , demonstrating non-inferiority of , on average , three tablets of PA21 vs. eight of sevelamer . Efficacy was maintained to week 24 . Non-adherence was 15.1 % ( PA21 ) vs. 21.3 % ( sevelamer ) . The percentage of patients that reported at least one treatment-emergent adverse event was 83.2 % with PA21 and 76.1 % with sevelamer . A higher proportion of patients withdrew owing to treatment-emergent adverse events with PA21 ( 15.7 % ) vs. sevelamer ( 6.6 % ) . Mild , transient diarrhea , discolored feces , and hyperphosphatemia were more frequent with PA21 ; nausea and constipation were more frequent with sevelamer . After 24 weeks , 99 hemodialysis patients on PA21 were re-r and omized into a 3-week superiority analysis of PA21 maintenance dose in 50 patients vs. low dose ( 250 mg per day ( ineffective control ) ) in 49 patients . The PA21 maintenance dose was superior to the low dose in maintaining serum phosphorus control . Thus , PA21 was effective in lowering serum phosphorus in dialysis patients , with similar efficacy to sevelamer carbonate , a lower pill burden , and better adherence Abstract Objective : Epidemiological data link elevated levels of serum phosphorus with increased mortality among patients with chronic kidney disease . Recent data also suggest improved survival with the use of dietary phosphate binders in patients on dialysis . However , few studies have comprehensively evaluated the survival benefit associated with different phosphate binders . A post-hoc survival analysis was undertaken of lanthanum carbonate ( Fosrenol * Fosrenol is a registered trademark of Shire Pharmaceuticals , Basingstoke , UK . ) versus st and ard therapy . Research design and methods : Patients on dialysis enrolled in a phase 3 , 2-year , comparative safety study were r and omized 1:1 to lanthanum carbonate or st and ard therapy to treat serum phosphorus to a target of ≤5.9 mg/dL ( 1.90 mmol/L ) . Patients ( N = 1354 ) were followed up for survival status during , or after completion of or discontinuation from the study . Main outcome measures : Survival was measured by time from first dose of study medication to all-cause mortality or last contact . Results : The distribution of follow-up time was similar in the lanthanum carbonate and st and ard therapy groups ( mean 23.7 versus 23.9 months [ median 27.0 versus 26.0 months ] , respectively ) . Serum phosphorus levels were similar across treatment groups , as patients were treated to target . At follow-up , 19.9 % ( 135/680 ) of patients treated with lanthanum carbonate had died versus 23.3 % ( 157/674 ) on st and ard therapy ( log-rank p = 0.18 ) . In the subgroup of patients aged > 65 years ( n = 336 ) , 27.0 % ( 44/163 ) of lanthanum-carbonate-treated patients had died compared with 39.3 % ( 68/173 ) on st and ard therapy ( log-rank p = 0.04 ) . Conclusion : In these survival analyses , overall mortality was similar in the lanthanum carbonate and st and ard therapy groups , but results suggest that there was a survival benefit associated with lanthanum carbonate treatment for patients aged > 65 years , who are likely to carry the greatest burden of vascular calcification . These results were similar to those observed in the Dialysis Clinical Outcomes Revisited study , a prospect i ve trial of sevelamer hydrochloride design ed to assess survival The risk of death in hemodialysis patients treated with calcium-containing phosphate binders or sevelamer is not known . We assessed all-cause mortality in 127 patients new to hemodialysis assigned to calcium-containing binders or sevelamer after a median follow-up of 44 months from r and omization . This was a predetermined secondary end point of a r and omized clinical trial design ed to assess progression of coronary artery calcium ( CAC ) scores in the two treatment arms . Thirty-four deaths occurred during the follow-up period : 23 in subjects r and omized to calcium-containing phosphate binders and 11 in subjects r and omized to sevelamer . Baseline CAC score was a significant predictor of mortality after adjustment for age , race , gender , and diabetes with increased mortality proportional to baseline score ( P=0.002 ) . Mortality was borderline significantly lower in subjects r and omized to sevelamer ( 5.3/100 patient years , confidence interval ( CI ) ( 2.2 - 8.5 ) compared to those r and omized to calcium-containing binders ( 10.6/100 patient years , CI 6.3 - 14.9 ) ( P=0.05 ) . The greater risk of death for patients treated with calcium-containing phosphate binders persisted after full multivariable adjustment ( P=0.016 , hazard ratio 3.1 , CI 1.23 - 7.61 ) . In subjects new to hemodialysis baseline CAC score was a significant predictor of all-cause mortality . Treatment with sevelamer was associated with a significant survival benefit as compared to the use of calcium-containing phosphate binders BACKGROUND Cardiovascular disease is frequent and severe in patients with end-stage renal disease . Disorders of mineral metabolism may contribute by promoting cardiovascular calcification . METHODS We conducted a r and omized clinical trial comparing sevelamer , a non-absorbed polymer , with calcium-based phosphate binders in 200 hemodialysis patients . Study outcomes included the targeted concentrations of serum phosphorus , calcium , and intact parathyroid hormone ( PTH ) , and calcification of the coronary arteries and thoracic aorta using a calcification score derived from electron beam tomography . RESULTS Sevelamer and calcium provided equivalent control of serum phosphorus ( end-of- study values 5.1 + /- 1.2 and 5.1 + /- 1.4 mg/dL , respectively , P = 0.33 ) . Serum calcium concentration was significantly higher in the calcium-treated group ( P = 0.002 ) , and hypercalcemia was more common ( 16 % vs. 5 % with sevelamer , P = 0.04 ) . More subjects in the calcium group had end-of- study intact PTH below the target of 150 to 300 pg/mL ( 57 % vs. 30 % , P = 0.001 ) . At study completion , the median absolute calcium score in the coronary arteries and aorta increased significantly in the calcium treated subjects but not in the sevelamer-treated subjects ( coronary arteries 36.6 vs. 0 , P = 0.03 and aorta 75.1 vs. 0 , P = 0.01 , respectively ) . The median percent change in coronary artery ( 25 % vs. 6 % , P = 0.02 ) and aortic ( 28 % vs. 5 % , P = 0.02 ) calcium score also was significantly greater with calcium than with sevelamer . CONCLUSIONS Compared with calcium-based phosphate binders , sevelamer is less likely to cause hypercalcemia , low levels of PTH , and progressive coronary and aortic calcification in hemodialysis patients BACKGROUND Elevated serum phosphorus and calcium are associated with arterial calcification and mortality in dialysis patients . Sevelamer , a phosphate-binding polymer , attenuates the progression of arterial calcification ; it is unknown whether this improves outcomes . PATIENTS AND INTERVENTIONS A r and omized comparison of sevelamer and calcium-based phosphate binders was performed in hemodialysis patients treated up to 45 months . The primary endpoint was mortality . Secondary endpoints included cause-specific mortality and hospitalization ; 2103 patients were r and omized , 2040 received treatment , and 1065 completed treatment . RESULTS Overall mortality was not significantly reduced by sevelamer ( adjusted relative risk = 0.92 ; 95 % confidence interval , 0.78 to 1.09 ; log-rank P = .40 ) . Among patients > or = 65 years of age , sevelamer reduced the risk of death ( adjusted relative risk = 0.77 ; 95 % confidence interval , 0.62 to 0.97 ; log-rank P = .02 ) . Sevelamer patients had a trend toward fewer hospitalizations ( P = .06 ) and fewer hospital days ( P = .09 ) . CONCLUSIONS A statistically significant reduction in mortality in the overall study population was not observed . Sevelamer was associated with a survival benefit among patients > or = 65 years of age BACKGROUND Whether the use of sevelamer rather than a calcium-containing phosphate binder improves cardiovascular ( CV ) survival in patients receiving dialysis remains to be eluci date d. STUDY DESIGN Open-label r and omized controlled trial with parallel groups . SETTING S & PARTICIPANTS 466 incident hemodialysis patients recruited from 18 centers in Italy . INTERVENTION Study participants were r and omly assigned in a 1:1 fashion to receive either sevelamer or a calcium-containing phosphate binder ( although not required by the protocol , all patients in this group received calcium carbonate ) for 24 months . OUTCOMES All individuals were followed up until completion of 36 months of follow-up or censoring . CV death due to cardiac arrhythmias was regarded as the primary end point . MEASUREMENTS Blind event adjudication . RESULTS At baseline , patients allocated to sevelamer had higher serum phosphorus ( mean , 5.6 ± 1.7 [ SD ] vs 4.8 ± 1.4 mg/dL ) and C-reactive protein levels ( mean , 8.8 ± 13.4 vs 5.9 ± 6.8 mg/dL ) and lower coronary artery calcification scores ( median , 19 [ IQR , 0 - 30 ] vs 30 [ IQR , 7 - 180 ] ) . At study completion , serum phosphate levels were lower in the sevelamer arm ( median dosages , 4,800 and 2,000 mg/d for sevelamer and calcium carbonate , respectively ) . After a mean follow-up of 28 ± 10 months , 128 deaths were recorded ( 29 and 88 due to cardiac arrhythmias and all-cause CV death ) . Sevelamer-treated patients experienced lower CV mortality due to cardiac arrhythmias compared with patients treated with calcium carbonate ( HR , 0.06 ; 95 % CI , 0.01 - 0.25 ; P < 0.001 ) . Similar results were noted for all-cause CV mortality and all-cause mortality , but not for non-CV mortality . Adjustments for potential confounders did not affect results . LIMITATIONS Open-label design , higher baseline coronary artery calcification burden in calcium carbonate-treated patients , different mineral metabolism control in sevelamer-treated patients , overall lower than expected mortality . CONCLUSIONS These results show that sevelamer compared to a calcium-containing phosphate binder improves survival in a cohort of incident hemodialysis patients . However , the better outcomes in the sevelamer group may be due to better phosphate control rather than reduction in calcium load Some propose using phosphate binders in the CKD population given the association between higher levels of phosphorus and mortality , but their safety and efficacy in this population are not well understood . Here , we aim ed to determine the effects of phosphate binders on parameters of mineral metabolism and vascular calcification among patients with moderate to advanced CKD . We r and omly assigned 148 patients with estimated GFR=20 - 45 ml/min per 1.73 m(2 ) to calcium acetate , lanthanum carbonate , sevelamer carbonate , or placebo . The primary endpoint was change in mean serum phosphorus from baseline to the average of months 3 , 6 , and 9 . Serum phosphorus decreased from a baseline mean of 4.2 mg/dl in both active and placebo arms to 3.9 mg/dl with active therapy and 4.1 mg/dl with placebo ( P=0.03 ) . Phosphate binders , but not placebo , decreased mean 24-hour urine phosphorus by 22 % . Median serum intact parathyroid hormone remained stable with active therapy and increased with placebo ( P=0.002 ) . Active therapy did not significantly affect plasma C-terminal fibroblast growth factor 23 levels . Active therapy did , however , significantly increase calcification of the coronary arteries and abdominal aorta ( coronary : median increases of 18.1 % versus 0.6 % , P=0.05 ; abdominal aorta : median increases of 15.4 % versus 3.4 % , P=0.03 ) . In conclusion , phosphate binders significantly lower serum and urinary phosphorus and attenuate progression of secondary hyperparathyroidism among patients with CKD who have normal or near-normal levels of serum phosphorus ; however , they also promote the progression of vascular calcification . The safety and efficacy of phosphate binders in CKD remain uncertain Elevated serum phosphorus is a predictable accompaniment of end-stage renal disease ( ESRD ) in the absence of dietary phosphate restriction or supplemental phosphate binders . The consequences of hyperphosphatemia include the development and progression of secondary hyperparathyroidism and a predisposition to metastatic calcification when the product of serum calcium and phosphorus ( Ca x PO4 ) is elevated . Both of these conditions may contribute to the substantial morbidity and mortality seen in patients with ESRD . We have analyzed the distribution of serum phosphorus in two large national , r and om , cross-sectional sample s of hemodialysis patients who have been receiving dialysis for at least 1 year . Data were obtained from two special studies of the United States Renal Data System , the Case Mix Adequacy Study ( 1990 ) and the Dialysis Morbidity and Mortality Study Wave 1 ( 1993 ) . The relative risk of death by serum phosphorus quintiles is described after adjusting for age at onset of ESRD , race , sex , smoking status , and the presence of diabetes , the acquired immunodeficiency syndrome , and /or neoplasm . Logistic regression analysis is then used to describe the demographic , comorbid , and laboratory parameters associated with high serum phosphorus . Serum phosphorus was similar in these two study population s and averaged 6.2 mg/dL. Ten percent of patients had levels greater than 9 mg/dL and at least 30 % of each group had serum phosphorus levels greater than 7 mg/dL. The adjusted relative risk of death by serum phosphorus level was not uniform across all quintiles , being constant below a level of 6.5 mg/dL and increasing significantly above this level . The relative risk of death for those with a serum phosphorus greater than 6.5 mg/dL was 1.27 relative to those with a serum phosphorus of 2.4 to 6.5 mg/dL. This increased risk was not diminished by statistical adjustment for coexisting medical conditions , delivered dose of dialysis , nutritional parameters , or markers of noncompliance . Evaluation of predictors of serum phosphorus greater than 6.5 mg/dL revealed in multivariate analysis that younger age at onset of ESRD , female sex , white race , diabetes , active smoking , and higher serum creatinine levels were all significant predictors . Analysis of serum calcium revealed no correlation with relative risk of death . The Ca x PO4 product , however , showed a mortality risk trend similar to that seen with serum phosphorus alone . Those in the highest quintile of the Ca x PO4 product ( > 72 mg2/dL2 ) had a relative mortality risk of 1.34 relative to those with products of 42 to 52 mg2/dL2 . The relative mortality risk by log parathyroid hormone ( PTH ) level was elevated for patients with higher levels , but the mortality risk associated with hyperphosphatemia was independent of PTH . For hemodialysis patients who have been receiving dialysis for at least 1 year , we conclude that a large percentage have a serum phosphorus level above 6.5 mg/dL and that this places them at increased risk of death . This increased risk is independent of PTH . The mechanism(s ) responsible for death is unknown , but may be related to an abnormally high Ca x PO4 product . Although mechanisms are not clearly established , this study supports the need for vigorous control of hyperphosphatemia to improve patient survival Background Hyperphosphatemia is a common complication in dialysis patients that can be treated by oral phosphate binders . We investigated the efficacy and safety of oral ferric citrate as a phosphate binder for Taiwanese patients with end stage renal disease and with hyperphosphatemia who were undergoing hemodialysis . Methods This was a prospect i ve , double-blind , placebo-controlled , r and omized trial carried out in 5 hospitals in Taiwan . Ferric citrate ( 4 or 6 g/day ) or placebo was administered for 56 days . Serum calcium , phosphorous levels , calcium × phosphorus product , serum ferritin level , transferrin saturation , and adverse events were recorded . Results A total of 166 patients completed the trial . The placebo group had relatively constant serum data . Serum phosphorus declined significantly in the 6 g/day group ( p < 0.05 for 4 and 8 weeks ) and the 4 g/day group ( p < 0.05 for 4 and 8 weeks ) . There were similar changes in the calcium × phosphorus product . The serum ferritin level increased significantly in the 6 g/day group ( p < 0.05 ) and the 4 g/day group ( p < 0.05 ) . There were similar changes in transferrin saturation . Most adverse events were mild to moderate and were comparable among the three groups . Conclusions A 56-day treatment with ferric citrate effectively controlled hyperphosphatemia and was well tolerated in maintenance hemodialysis patients . There were also moderate increases in serum ferritin and transferrin saturation Abstract Background : Cardiac valve calcification ( CVC ) and left ventricular ( LV ) alterations are frequent complication in end-stage renal disease ( ESRD ) . We determined the prevalence of CVC and LV hypertrophy ( LVH ) in ESRD patients before renal replacement therapy and 12 months after peritoneal dialysis ( PD ) . Methods : A prospect i ve longitudinal of 50 incident PD patients was studied . Demographic and clinical data were recorded and blood assayed at baseline and after 1-year of follow-up . CVC and LVH were evaluated by M-mode two-dimensional echocardiography . Results : CVC of the mitral and aortic valves and of both valves were noted in 30 , 18 and 10 % of patients , respectively . After 12 months of PD regimen , 20 % patients had aortic , 24 % mitral and 8 % had calcification of both valves . After one year of PD , LVH was 62 and 36 % in patients with and without CVC , respectively ( p < 0.05 ) . Endothelin-1 is an independent predictor of CVC at the baseline , while nitric oxide is inversely an independent predictor at the end of follow-up . Conclusions : CVC is associated with LVH in PD patients . These findings identified a potential role for monitored markers to be incorporated into therapeutic strategies aim ed at detection and treatment of cardiovascular complications and prevention strategies Patients on dialysis require phosphorus binders to prevent hyperphosphatemia and are iron deficient . We studied ferric citrate as a phosphorus binder and iron source . In this sequential , r and omized trial , 441 subjects on dialysis were r and omized to ferric citrate or active control in a 52-week active control period followed by a 4-week placebo control period , in which subjects on ferric citrate who completed the active control period were rer and omized to ferric citrate or placebo . The primary analysis compared the mean change in phosphorus between ferric citrate and placebo during the placebo control period . A sequential gatekeeping strategy controlled study -wise type 1 error for serum ferritin , transferrin saturation , and intravenous iron and erythropoietin-stimulating agent usage as prespecified secondary outcomes in the active control period . Ferric citrate controlled phosphorus compared with placebo , with a mean treatment difference of -2.2±0.2 mg/dl ( mean±SEM ) ( P<0.001 ) . Active control period phosphorus was similar between ferric citrate and active control , with comparable safety profiles . Subjects on ferric citrate achieved higher mean iron parameters ( ferritin=899±488 ng/ml [ mean±SD ] ; transferrin saturation=39%±17 % ) versus subjects on active control ( ferritin=628±367 ng/ml [ mean±SD ] ; transferrin saturation=30%±12 % ; P<0.001 for both ) . Subjects on ferric citrate received less intravenous elemental iron ( median=12.95 mg/wk ferric citrate ; 26.88 mg/wk active control ; P<0.001 ) and less erythropoietin-stimulating agent ( median epoetin-equivalent units per week : 5306 units/wk ferric citrate ; 6951 units/wk active control ; P=0.04 ) . Hemoglobin levels were statistically higher on ferric citrate . Thus , ferric citrate is an efficacious and safe phosphate binder that increases iron stores and reduces intravenous iron and erythropoietin-stimulating agent use while maintaining hemoglobin BACKGROUND AND OBJECTIVES Dietary phosphorous overload and excessive calcium intake from calcium-containing phosphate binders promote coronary artery calcification ( CAC ) that may contribute to high mortality of dialysis patients . CAC has been found in patients in early stages of nondialysis-dependent CKD . In this population , no study has evaluated the potential role of phosphorus binders on mortality . This study aim ed to evaluate all-cause mortality as the primary end point in nondialysis-dependent CKD patients r and omized to different phosphate binders ; secondary end points were dialysis inception and the composite end point of all-cause mortality and dialysis inception . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS This is a r and omized , multicenter , nonblinded pilot study . Consecutive out patients ( n=212 ; stage 3 - 4 CKD ) were r and omized to either sevelamer ( n=107 ) or calcium carbonate ( n=105 ) . Phosphorus concentration was maintained between 2.7 and 4.6 mg/dl for patients with stage 3 - 4 CKD and between 3.5 and 5.5 mg/dl for patients with stage 5 CKD . The CAC score was assessed by computed tomography at study entry and after 6 , 12 , 18 , and 24 months . All-cause mortality , dialysis inception , and the composite end point were recorded for up to 36 months . RESULTS In patients r and omized to sevelamer , all-cause mortality and the composite end point were lower ; a nonsignificant trend was noted for dialysis inception . CONCLUSIONS Sevelamer provided benefits in all-cause mortality and in the composite end point of death or dialysis inception but not advantages in dialysis inception . Larger studies are needed to confirm these results BACKGROUND Previous clinical trials showed that progression of coronary artery calcification ( CAC ) may be slower in hemodialysis patients treated with sevelamer than those treated with calcium-based phosphate binders . Because sevelamer decreases low-density lipoprotein cholesterol ( LDL-C ) levels , we hypothesized that intensive lowering of LDL-C levels with atorvastatin in hemodialysis patients treated with calcium acetate would result in CAC progression rates similar to those in sevelamer-treated patients . STUDY DESIGN R and omized , controlled , open-label , noninferiority trial with an upper bound for the noninferiority margin of 1.8 . SETTING & PARTICIPANTS 203 prevalent hemodialysis patients at 26 dialysis centers with serum phosphorus levels greater than 5.5 mg/dL , LDL-C levels greater than 80 mg/dL , and baseline CAC scores of 30 to 7,000 units assessed by means of electron-beam computed tomography . INTERVENTIONS 103 patients were r and omly assigned to calcium acetate , and 100 patients to sevelamer for 12 months to achieve phosphorus levels of 3.5 to 5.5 mg/dL. Atorvastatin was added to achieve serum LDL-C levels less than 70 mg/dL in both groups . OUTCOMES & MEASUREMENTS The primary end point was change in CAC score assessed by means of electron-beam computed tomography . RESULTS After 12 months , mean serum LDL-C levels decreased to 68.8 + /- 22.0 mg/dL in the calcium-acetate group and 62.4 + /- 23.0 mg/dL in the sevelamer group ( P = 0.3 ) . Geometric mean increases in CAC scores were 35 % in the calcium-acetate group and 39 % in the sevelamer group , with a covariate-adjusted calcium acetate-sevelamer ratio of 0.994 ( 95 % confidence interval , 0.851 to 1.161 ) . LIMITATIONS Treatment assignment was not blinded . The 1.8 a priori margin is large , CAC is a surrogate outcome , duration of treatment was short , and dropout rate was high . CONCLUSIONS With intensive lowering of LDL-C levels for 1 year , hemodialysis patients treated with either calcium acetate or sevelamer experienced similar progression of CAC Background and Objectives : Coronary artery calcification ( CAC ) is associated with future cardiovascular events and /or death of patients on hemodialysis ( HD ) . We investigated whether progression of CAC in patients on HD could be delayed by switching from a calcium (Ca)-based phosphate ( Pi ) binder to lanthanum carbonate . Design , Setting , Participants , and Measurements : The CAC scores were evaluated at study enrollment and after 6 months in 52 patients on HD using calcium carbonate ( CC ) as a Pi binder . Patients were r and omly divided into 2 groups assigned to receive either CC or lanthanum carbonate ( LC ) , and the CAC scores were evaluated after a 6-month treatment period . Progression of CAC was assessed , as were serum levels of Ca , Pi , and intact parathyroid hormone ( iPTH ) . Results : Forty-two patients completed the study ( 23 receiving CC and 19 receiving LC ) . In the 6 months prior to r and omization , all patients were treated with CC . During this 6-month period , the CAC scores increased significantly in all 42 patients . Once r and omized , there was significantly less progression in the group treated with LC than with CC . Changes in CAC scores from 6 to 12 months were significantly smaller in the LC group than the CC group ( −288.9 ± 1176.4 vs 107.1 ± 559.6 , P = .036 ) , and percentage changes were also significantly different ( −6.4 % vs 41.2 % , P = .024 ) . Serum Ca , Pi , and iPTH levels were similar in both groups during the study period . Conclusions : This pilot study suggested that LC delayed progression of CAC in patients on HD compared with CC BACKGROUND Vascular calcification ( VC ) contributes to cardiovascular disease in haemodialysis ( HD ) patients . Few controlled studies have addressed interventions to reduce VC but non-calcium-based phosphate binders may be beneficial . No published r and omized study to date has assessed the effect of lanthanum carbonate ( LC ) on VC progression . METHODS We conducted a pilot r and omized controlled trial to determine the effect of LC on VC . Forty-five HD patients were r and omized to either LC or calcium carbonate ( CC ) . Primary outcome was change in aortic VC after 18 months . Secondary outcomes included superficial femoral artery ( SFA ) VC , bone mineral density ( BMD ) of lumbar spine and serum markers of mineral metabolism . At baseline , 6 and 18 month computed tomography was performed to measure VC and BMD . A r and om effect linear regression model was performed to assess differences . RESULTS Thirty patients completed the study ( 17 LC , 13 CC ) ; baseline median age 58 years , 38 % diabetic , 64 % male . Ninety-three per cent had aortic VC at commencement and 87 % showed progression . At 18 months , there was significantly less aortic VC progression with LC than CC ( adjusted difference -98.1 ( -149.4 , -46.8 ) Hounsfield units ( HU ) , P < 0.001 ) . There was also a non-significant reduction with LC in left SFA VC ( -25.8 ( -67.7 , 16.1 ) HU , P = 0.2 ) and right SFA VC ( -35.9 ( -77.8 , 5.9 ) HU , P = 0.09 ) . There was no difference in lumbar spine BMD and serum phosphate , calcium and parathyroid hormone levels between groups . Limitations to the study include small sample size and loss to follow up . CONCLUSIONS Lanthanum carbonate was associated with reduced progression of aortic calcification compared with CC in HD patients over 18 months BACKGROUND Hyperphosphatemia is a common complication in end-stage renal disease ( ESRD ) patients . Reducing the serum phosphate level is crucial in management of ESRD . METHODS This study was a r and omized prospect i ve study , design ed to compare patients with hyperphosphatemia undergoing peritoneal dialysis while taking lanthanum carbonate or calcium carbonate . We divided 72 continuous ambulatory peritoneal dialysis ( CAPD ) patients whose serum phosphate levels were over 5.6 mg/dl into two groups to receive either lanthanum carbonate or calcium carbonate . Serum calcium , phosphate and PTH levels were examined serially for 24 weeks . RESULTS Both lanthanum carbonate and calcium carbonate reduced serum phosphate levels , from 6.79 ± 1.05 to 5.44 ± 1.44 and from 6.31 ± 1.13 to 4.74 ± 0.78 mg/dl , respectively . The calcium × phosphate product level was reduced in the lanthanum carbonate and calcium carbonate groups from 60.23 ± 10.23 to 46.97 ± 16.42 and from 57.92 ± 11.05 to 44.50 ± 7.74 mg2/dl2 , respectively . The serum parathyroid hormone ( PTH ) level in the lanthanum carbonate group did not change significantly compared to baseline during the study , but in the calcium carbonate group , the serum PTH level decreased significantly . Gastrointestinal complications were the main adverse effects of lanthanum carbonate and 11 out of 35 patients dropped out of the study due to this complication . CONCLUSIONS Lanthanum carbonate was as effective as calcium carbonate in reducing serum phosphate level , and serum PTH level tended to be steadier in the lanthanum carbonate group compared to the calcium carbonate group . Though the ifference was not significant , lanthanum carbonate tended not to elevate serum calcium level in CAPD patients compared to calcium carbonate . The high incidence of gastrointestinal adverse effect in the lanthanum carbonate group will need further evaluation BACKGROUND Some trials have indicated that coronary artery calcification progresses more slowly in sevelamer-treated dialysis patients than in those using calcium-based binders . Effects of phosphate binders on circulating advanced glycation end products ( AGEs ) are unknown . STUDY DESIGN R and omized trial with parallel-group design . SETTING & PARTICIPANTS 183 adult ( aged > 20 years ) patients on maintenance hemodialysis therapy at 12 dialysis facilities with a mean vintage of 118 ± 89 ( median , 108 ) months . Dialysate calcium concentration was 2.5 mEq/L , and dietary calcium was not controlled . INTERVENTION Patients were r and omly assigned to 12 months of treatment with sevelamer ( n = 91 ) or calcium carbonate ( n = 92 ) . OUTCOMES & MEASUREMENTS Primary outcome measures were change from baseline in coronary artery calcification score ( CACS ) determined at study entry and completion using multislice computed tomography and the proportion of patients with a ≥ 15 % increase in CACS . Blood parameters were determined at study entry and 2-week intervals , and levels of plasma pentosidine , a representative AGE , were determined at study entry , 6 months , and study completion . RESULTS 79 ( 86.8 % ) and 84 ( 91.3 % ) patients in the sevelamer and calcium-carbonate arms completed the treatment , respectively . Both binders were associated with an increase in mean CACS : 81.8 ( 95 % CI , 42.9 - 120.6 ) and 194.0 ( 139.7 - 248.4 ) , respectively ( P < 0.001 for both ) . After adjustment for baseline values , the increase in the sevelamer group was 112.3 ( 45.8 - 178 ) less ( P < 0.001 ) . Percentages of patients with a ≥ 15 % increase in CACS were 35 % of the sevelamer group and 59 % of the calcium-carbonate group ( P = 0.002 ) . Plasma pentosidine levels increased with calcium carbonate but not [ corrected ] sevelamer treatment ( P < 0.001 ) . Sevelamer use was associated with decreased risk of a ≥ 15 % increase in CACS regardless of baseline blood parameters , pentosidine level , and CACS . LIMITATIONS Treatment duration was relatively short , some sevelamer-treated patients ( 7 of 79 ) received calcium carbonate , and washout could not be performed . CONCLUSIONS The data suggest that sevelamer treatment slowed the increase in CACS and suppressed AGE accumulation BACKGROUND AND OBJECTIVES A dose-finding study was undertaken to investigate the efficacy of PA21 , a novel polynuclear iron(III)-oxyhydroxide phosphate binder . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS In a r and omized , active-controlled , multicenter , open-label study at 50 clinical sites in Europe and the United States , hemodialysis patients were r and omized to PA21 at dosages of 1.25 , 5.0 , 7.5 , 10.0 , or 12.5 g/d or sevelamer-HCl 4.8 g/d for 6 weeks . The primary efficacy endpoint was the change in serum phosphorus concentration from baseline . RESULTS There were 154 participants who were r and omized and received the study drug . All groups except PA21 1.25 g/d showed a significant decrease in serum phosphorus . Mean decreases in serum phosphorus in PA21 10 g/d and 12.5 g/d were -2.00±1.71 mg/dl and -1.69±1.81 mg/dl , respectively . A similar decrease to sevelamer-HCl ( -1.06±1.35 mg/dl ) was seen with PA21 5.0 g/d ( -1.08±2.12 mg/dl ) and 7.5 g/d ( -1.25±1.21 mg/d ) . Overall , 60.9 % of participants r and omized to PA21 and 57.7 % r and omized to sevelamer-HCl reported ≥1 adverse event . The most frequent adverse events were hypophosphatemia ( 18.0 % ) and discolored feces ( 11.7 % ) for the pooled PA21 dose groups , and diarrhea , hypophosphatemia , and hypotension ( each 11.5 % ) for sevelamer-HCl . Discontinuation due to adverse events occurred at a similar rate in PA21-treated ( 21.1 % ) and sevelamer-HCl-treated ( 23.1 % ) participants . CONCLUSIONS PA21 5 - 12.5 g/d significantly reduces serum phosphorus in hemodialysis patients . The 5 g/d and 7.5 g/d dosages showed similar efficacy to 4.8 g/d of sevelamer-HCl . The adverse events rate was similar for PA21 and sevelamer-HCl |
13,848 | 26,959,055 | Overall , most of the nutritional interventions tested by the selected RCTs were found to produce statistically significant cognitive benefits ( defined as improved neuropsychological test scores ) .
Results of the present review suggest that several dietary patterns and nutritional components may constitute promising strategies in postponing , slowing , and preventing cognitive decline . | In recent years , the possibility of favorably influencing the cognitive trajectory through promotion of lifestyle modifications has been increasingly investigated .
In particular , the relationship between nutritional habits and cognitive health has attracted special attention .
The present review is design ed to retrieve and discuss recent evidence ( published over the last 3 years ) coming from r and omized controlled trials ( RCTs ) investigating the efficacy of nutritional interventions aim ed at improving cognitive functioning and /or preventing cognitive decline in non-demented older individuals . | Abstract 1680 participants were r and omized over the recruitment period in MAPT study . A total of 1290 participants were recruited in the 7 University Hospital centers , and 390 participants in the 6 memory clinics around Toulouse Gerontopole / Alzheimer Disease research clinical center . The first r and omization was on May 30 , 2008 , and the targeted number of r and omized participants was reached on February 24 , 2011 ; 2595 subjects were finally screened , of which 1680 fulfilled the eligibility criteria which represents 64.8 % . Approximately , one quarter of screened people refused to participate after the detailed presentation of the study and 4.3 % were still interested in participating but missed for unknown reasons the baseline visit even after repeated contacts . Of the 1810 subjects who signed the consent for participating to the study at the baseline visit , 130 ( 7.1 % ) were excluded because one of the eligibility criteria was not satisfied . Interestingly , the higher percentage of r and omizations compared to screened participants is the personal contact source ; almost 85 % of screened participants entered in the study . In an equivalent way , Medias and conferences are efficient recruiting sources to enrol volunteers in the study . Unexpectedly , only about 60 % of screened participants from the hospital and GP sources were r and omized and 33.2 % from health care services . Almost a quarter of the r and omized participants come from the hospital out patients clinics and approximately 20 % from public conferences . A total of 1128 contacts yielded to 556 screened volunteers and 345 r and omized participants in the coordinating center of Toulouse . Thus , 30 % of contacts were recruited Purpose To assess the effects of creatine supplementation , associated or not with strength training , upon emotional and cognitive measures in older woman . Methods This is a 24-week , parallel-group , double-blind , r and omized , placebo-controlled trial . The individuals were r and omly allocated into one of the following groups ( n=14 each ) : 1 ) placebo , 2 ) creatine supplementation , 3 ) placebo associated with strength training or 4 ) creatine supplementation associated with strength training . According to their allocation , the participants were given creatine ( 4 x 5 g/d for 5 days followed by 5 g/d ) or placebo ( dextrose at the same dosage ) and were strength trained or not . Cognitive function , assessed by a comprehensive battery of tests involving memory , selective attention , and inhibitory control , and emotional measures , assessed by the Geriatric Depression Scale , were evaluated at baseline , after 12 and 24 weeks of the intervention . Muscle strength and food intake were evaluated at baseline and after 24 weeks . Results After the 24-week intervention , both training groups ( ingesting creatine supplementation and placebo ) had significant reductions on the Geriatric Depression Scale scores when compared with the non-trained placebo group ( p = 0.001 and p = 0.01 , respectively ) and the non-trained creatine group ( p < 0.001 for both comparison ) . However , no significant differences were observed between the non-trained placebo and creatine ( p = 0.60 ) groups , or between the trained placebo and creatine groups ( p = 0.83 ) . Both trained groups , irrespective of creatine supplementation , had better muscle strength performance than the non-trained groups . Neither strength training nor creatine supplementation altered any parameter of cognitive performance . Food intake remained unchanged . Conclusion Creatine supplementation did not promote any significant change in cognitive function and emotional parameters in apparently healthy older individuals . In addition , strength training per se improved emotional state and muscle strength , but not cognition , with no additive effects of creatine supplementation . Trial Registration Clinical trials.gov BACKGROUND Research indicates that the chronic consumption of flavonoids is associated with cognitive benefits in adults with mild cognitive impairment and neurodegenerative disease , although to our knowledge , there have been no such studies in healthy older adults . Furthermore , the effects of commonly consumed orange juice flavanones on cognitive function remain unexplored . OBJECTIVE We investigated whether 8 wk of daily flavanone-rich orange juice consumption was beneficial for cognitive function in healthy older adults . DESIGN High-flavanone ( 305 mg ) 100 % orange juice and an equicaloric low-flavanone ( 37 mg ) orange-flavored cordial ( 500 mL ) were consumed daily for 8 wk by 37 healthy older adults ( mean age : 67 y ) according to a crossover , double-blind , r and omized design separated by a 4-wk washout . Cognitive function , mood , and blood pressure were assessed at baseline and follow-up by using st and ardized vali date d tests . RESULTS Global cognitive function was significantly better after 8-wk consumption of flavanone-rich juice than after 8-wk consumption of the low-flavanone control . No significant effects on mood or blood pressure were observed . CONCLUSIONS Chronic daily consumption of flavanone-rich 100 % orange juice over 8 wk is beneficial for cognitive function in healthy older adults . The potential for flavanone-rich foods and drinks to attenuate cognitive decline in aging and the mechanisms that underlie these effects should be investigated IMPORTANCE Oxidative stress and vascular impairment are believed to partly mediate age-related cognitive decline , a strong risk factor for development of dementia . Epidemiologic studies suggest that a Mediterranean diet , an antioxidant-rich cardioprotective dietary pattern , delays cognitive decline , but clinical trial evidence is lacking . OBJECTIVE To investigate whether a Mediterranean diet supplemented with antioxidant-rich foods influences cognitive function compared with a control diet . DESIGN , SETTING , AND PARTICIPANTS Parallel-group r and omized clinical trial of 447 cognitively healthy volunteers from Barcelona , Spain ( 233 women [ 52.1 % ] ; mean age , 66.9 years ) , at high cardiovascular risk were enrolled into the Prevención con Dieta Mediterránea nutrition intervention trial from October 1 , 2003 , through December 31 , 2009 . All patients underwent neuropsychological assessment at inclusion and were offered retesting at the end of the study . INTERVENTIONS Participants were r and omly assigned to a Mediterranean diet supplemented with extravirgin olive oil ( 1 L/wk ) , a Mediterranean diet supplemented with mixed nuts ( 30 g/d ) , or a control diet ( advice to reduce dietary fat ) . MAIN OUTCOMES AND MEASURES Rates of cognitive change over time based on a neuropsychological test battery : Mini-Mental State Examination , Rey Auditory Verbal Learning Test ( RAVLT ) , Animals Semantic Fluency , Digit Span subtest from the Wechsler Adult Intelligence Scale , Verbal Paired Associates from the Wechsler Memory Scale , and the Color Trail Test . We used mean z scores of change in each test to construct 3 cognitive composites : memory , frontal ( attention and executive function ) , and global . RESULTS Follow-up cognitive tests were available in 334 participants after intervention ( median , 4.1 years ) . In multivariate analyses adjusted for confounders , participants allocated to a Mediterranean diet plus olive oil scored better on the RAVLT ( P = .049 ) and Color Trail Test part 2 ( P = .04 ) compared with controls ; no between-group differences were observed for the other cognitive tests . Similarly adjusted cognitive composites ( mean z scores with 95 % CIs ) for changes above baseline of the memory composite were 0.04 ( -0.09 to 0.18 ) for the Mediterranean diet plus olive oil , 0.09 ( -0.05 to 0.23 ; P = .04 vs controls ) for the Mediterranean diet plus nuts , and -0.17 ( -0.32 to -0.01 ) for the control diet . Respective changes from baseline of the frontal cognition composite were 0.23 ( 0.03 to 0.43 ; P = .003 vs controls ) , 0.03 ( -0.25 to 0.31 ) , and -0.33 ( -0.57 to -0.09 ) . Changes from baseline of the global cognition composite were 0.05 ( -0.11 to 0.21 ; P = .005 vs controls ) for the Mediterranean diet plus olive oil , -0.05 ( -0.27 to 0.18 ) for the Mediterranean diet plus nuts , and -0.38 ( -0.57 to -0.18 ) for the control diet . All cognitive composites significantly ( P < .05 ) decreased from baseline in controls . CONCLUSIONS AND RELEVANCE In an older population , a Mediterranean diet supplemented with olive oil or nuts is associated with improved cognitive function . TRIAL REGISTRATION is rct n.org Identifier : IS RCT N35739639 Recent epidemiological studies have indicated numerous associations between vascular and lifestyle related risk factors and incident dementia . However , evidence from r and omised controlled trials ( RCT ) showing effectiveness of interventions aim ed at these risk factors in preventing or postponing dementia onset is still lacking . Three large RCTs on multi-component interventions to prevent dementia ( preDIVA , FINGER , MAPT ) have been initiated in Europe to address these issues . Irrespective of some method ological differences , all three studies target cardiovascular and lifestyle related risk factors . Collaboration within the newly founded ' European Dementia Prevention Initiative ' ( EDPI ) will allow for a comprehensive exploration of optimal target population , intervention and outcome measures , which are currently unknown . Combining data of the ongoing studies and running simulation analyses will facilitate determining the optimal design including accurate sample -size calculations for future multi-national clinical trials on dementia prevention . Interventions aim ing at dementia prevention should be pragmatic and easy to implement on a large scale in different health care systems , without generating high additional costs or burden on participants or physicians . As the optimal age for intervention precedes the optimal age for outcome assessment , traditional trial design s might lead to suboptimal timing of either of the two . Separation of intervention and outcome assessment in time is a potential solution , but requires studies with very long follow-up . International collaboration of research groups with experience in dementia prevention studies and well-organised logistics for these major projects is pivotal to success for future large-scale dementia prevention studies . Founding of EDPI is an important first step in this direction Background and Purpose Cardiovascular risk factors are associated with an increased risk of dementia . Treatment of hypertension and hypercholesterolemia is associated with a decrease in incident dementia . Whether interventions aim ed at cardiovascular risk factors in late life also reduce dementia risk is unknown . Here , we report the outline of a pragmatic study that will attempt to answer this question and we describe the prevalence of cardiovascular risk factors in the target population . Methods We design ed a large cluster-r and omized trial with a 6-year follow-up in 3700 elderly subjects ( 70 to 78 y ) to assess whether nurse-led intensive vascular care in primary care decreases the incidence of dementia and reduces disability . Secondary outcome parameters are mortality , incidence of vascular events , and cognitive functioning . Intensive vascular care comprises treatment of hypertension , hypercholesterolemia , diabetes and reducing overweight , smoking cessation , and stimulating physical exercise . Results Baseline data of 1004 subjects show that 87 % of the subjects have 1 or more cardiovascular risk factors and 44 % have even 2 or more risk factors amenable to treatment . Seventy-nine percent of the subjects receiving antihypertensive medication still have a systolic pressure of > 140 mm Hg . Conclusions In this older age group , the very high percentage of elderly subjects with cardiovascular risk factors illustrates the large window of opportunity for therapies directed to lower the cardiovascular risk and potentially also the risk for dementia BACKGROUND Modifiable vascular and lifestyle-related risk factors have been associated with dementia risk in observational studies . In the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability ( FINGER ) , a proof-of-concept r and omised controlled trial , we aim ed to assess a multidomain approach to prevent cognitive decline in at-risk elderly people from the general population . METHODS In a double-blind r and omised controlled trial we enrolled individuals aged 60 - 77 years recruited from previous national surveys . Inclusion criteria were CAIDE ( Cardiovascular Risk Factors , Aging and Dementia ) Dementia Risk Score of at least 6 points and cognition at mean level or slightly lower than expected for age . We r and omly assigned participants in a 1:1 ratio to a 2 year multidomain intervention ( diet , exercise , cognitive training , vascular risk monitoring ) , or a control group ( general health advice ) . Computer-generated allocation was done in blocks of four ( two individuals r and omly allocated to each group ) at each site . Group allocation was not actively disclosed to participants and outcome assessors were masked to group allocation . The primary outcome was change in cognition as measured through comprehensive neuropsychological test battery ( NTB ) Z score . Analysis was by modified intention to treat ( all participants with at least one post-baseline observation ) . This trial is registered at Clinical Trials.gov , number NCT01041989 . FINDINGS Between Sept 7 , 2009 , and Nov 24 , 2011 , we screened 2654 individuals and r and omly assigned 1260 to the intervention group ( n=631 ) or control group ( n=629 ) . 591 ( 94 % ) participants in the intervention group and 599 ( 95 % ) in the control group had at least one post-baseline assessment and were included in the modified intention-to-treat analysis . Estimated mean change in NTB total Z score at 2 years was 0·20 ( SE 0·02 , SD 0·51 ) in the intervention group and 0·16 ( 0·01 , 0·51 ) in the control group . Between-group difference in the change of NTB total score per year was 0·022 ( 95 % CI 0·002 - 0·042 , p=0·030 ) . 153 ( 12 % ) individuals dropped out overall . Adverse events occurred in 46 ( 7 % ) participants in the intervention group compared with six ( 1 % ) participants in the control group ; the most common adverse event was musculoskeletal pain ( 32 [ 5 % ] individuals for intervention vs no individuals for control ) . INTERPRETATION Findings from this large , long-term , r and omised controlled trial suggest that a multidomain intervention could improve or maintain cognitive functioning in at-risk elderly people from the general population . FUNDING Academy of Finl and , La Carita Foundation , Alzheimer Association , Alzheimer 's Research and Prevention Foundation , Juho Vainio Foundation , Novo Nordisk Foundation , Finnish Social Insurance Institution , Ministry of Education and Culture , Salama bint Hamdan Al Nahyan Foundation , Axa Research Fund , EVO funding for University Hospitals of Kuopio , Oulu , and Turku and for Seinäjoki Central Hospital and Oulu City Hospital , Swedish Research Council , Swedish Research Council for Health , Working Life and Welfare , and af Jochnick Foundation The dentate gyrus ( DG ) is a region in the hippocampal formation whose function declines in association with human aging and is therefore considered to be a possible source of age-related memory decline . Causal evidence is needed , however , to show that DG-associated memory decline in otherwise healthy elders can be improved by interventions that enhance DG function . We addressed this issue by first using a high-resolution variant of functional magnetic resonance imaging ( fMRI ) to map the precise site of age-related DG dysfunction and to develop a cognitive task whose function localized to this anatomical site . Then , in a controlled r and omized trial , we applied these tools to study healthy 50–69-year-old subjects who consumed either a high or low cocoa flavanol – containing diet for 3 months . A high-flavanol intervention was found to enhance DG function , as measured by fMRI and by cognitive testing . Our findings establish that DG dysfunction is a driver of age-related cognitive decline and suggest non-pharmacological means for its amelioration Purpose Maintenance of cognitive abilities is important for elderly to stay independent . With the aging of the population , the call for modifiable factors is emerging . Dietary protein might improve cognitive performance ; however , this has hardly been studied . Therefore , we studied the impact of 24-week dietary protein supplementation on cognitive performance in pre-frail and frail elderly people . Methods Pre-frail and frail elderly subjects , according to the Fried criteria , r and omly received a protein drink containing 15 g protein or a placebo drink twice a day . Cognitive performance was measured at baseline and after 24 weeks by means of a sensitive neuropsychological test battery . In addition , reaction time was assessed after both 12 and 24 weeks of intervention . Domain scores were calculated for the domains episodic memory , attention and working memory , information processing speed , and executive functioning . Analyses of covariance were used to determine differences between groups . Linear mixed models were used to determine differences in reaction time over time and per treatment . Results In total , 65 subjects ( 79 ± 8 years ) with a median Mini-Mental State Examination score of 28 ( interquartile range 26–30 ) were included . Reaction time improved more in the protein group ( 68 ms ) than in the placebo group ( 18 ms , P = 0.03 ) . Dietary protein had no significant effect on any of the cognitive domain scores . Conclusions Protein supplementation might improve reaction time performance in pre-frail and frail elderly , but did not improve other cognitive functions Objective XXXto assess the effect on cognition of a controlled intervention testing Mediterranean diets ( MedDiet ) . Design XXXr and omized trial after 6.5 years of nutritional intervention . Setting Eight primary care centers affiliated to the University of Navarra . Participants A r and om sub sample of 285 participants ( 95 r and omly allocated to each of 3 groups ) of the PREDIMED-NAVARRA trial . All of them were at high vascular risk ( 44.8 % men , 74.1± 5.7 years at cognitive evaluation ) . Interventions Nutritional intervention comparing two MedDiets ( supplemented with extra-virgin olive oil [ EVOO ] or mixed nuts ) versus a low-fat control diet . Participants received intensive education to increase adherence to the intended intervention . Participants allocated to the MedDiet groups received EVOO ( 1 l/week ) or 30 g/day of mixed nuts . Dietary habits were evaluated using a vali date d 137-item food frequency question naire ( FFQ ) . Additionally , adherence to MedDiet was appraised using a 14-item question naire both at baseline and yearly thereafter . Measurements XXXcognitive performance as a main outcome and cognitive status ( normal , mild cognitive impairment [ MCI ] or dementia ) as a secondary outcome were evaluated by two neurologists blinded to group assignment after 6.5 years of nutritional intervention . Results Better post-trial cognitive performance versus control in all cognitive domains and significantly better performance across fluency and memory tasks were observed for participants allocated to the MedDiet+EVOO group . After adjustment for sex , age , education , apolipoprotein E genotype , family history of cognitive impairment/dementia , smoking , physical activity , body mass index , hypertension , dyslipidaemia , diabetes , alcohol and total energy intake , this group also showed lower MCI ( OR=0.34 95 % CI : 0.12–0.97 ) compared with control group . Participants assigned to MedDiet+Nuts group did not differ from controls . Conclusion A long-term intervention with an EVOO-rich MedDiet result ed in a better cognitive function in comparison with a control diet . However , non-significant differences were found for most cognitive domains . Participants allocated to an EVOO-rich MedDiet had less MCI than controls Objective Previous observational studies reported beneficial effects of the Mediterranean diet ( MedDiet ) on cognitive function , but results were inconsistent . We assessed the effect on cognition of a nutritional intervention using MedDiets in comparison with a low-fat control diet . Methods We assessed 522 participants at high vascular risk ( 44.6 % men , age 74.6 ± 5.7 years at cognitive evaluation ) enrolled in a multicentre , r and omised , primary prevention trial ( PREDIMED ) , after a nutritional intervention comparing two MedDiets ( supplemented with either extra-virgin olive oil ( EVOO ) or mixed nuts ) versus a low-fat control diet . Global cognitive performance was examined by Mini-Mental State Examination ( MMSE ) and Clock Drawing Test ( CDT ) after 6.5 years of nutritional intervention . Research ers who assessed the outcome were blinded to group assignment . We used general linear models to control for potential confounding . Results After adjustment for sex , age , education , Apolipoprotein E genotype , family history of cognitive impairment/dementia , smoking , physical activity , body mass index , hypertension , dyslipidaemia , diabetes , alcohol and total energy intake , participants allocated to the MedDiet+EVOO showed higher mean MMSE and CDT scores with significant differences versus control ( adjusted differences : + 0.62 95 % CI + 0.18 to + 1.05 , p=0.005 for MMSE , and + 0.51 95 % CI + 0.20 to + 0.82 , p=0.001 for CDT ) . The adjusted means of MMSE and CDT scores were also higher for participants allocated to the MedDiet+Nuts versus control ( adjusted differences : + 0.57 ( 95 % CI + 0.11 to + 1.03 ) , p=0.015 for MMSE and + 0.33 ( 95 % CI + 0.003 to + 0.67 ) , p=0.048 for CDT ) . These results did not differ after controlling for incident depression . Conclusions An intervention with MedDiets enhanced with either EVOO or nuts appears to improve cognition compared with a low-fat diet . IS RCT BACKGROUND Experimental evidence s have demonstrated that Nigella sativa Linn . seed ( NS ) has positive modulation effects on aged rats with memory impairments , prevents against hippocampal pyramidal cell loss and enhances consolidation of recall capability of stored information and spatial memory in rats . NS has neuroprotective , nephroprotective , lung protective , cardioprotective , hepatoprotective activities as established by previous studies on animals . Several clinical trials with NS on human have also demonstrated beneficial effect . AIM OF THE STUDY The present study was design ed to investigate the effects of NS on memory , attention and cognition in healthy elderly volunteers . Furthermore , safety profile of NS was assessed during the nine-week study period . METHODS Forty elderly volunteers were recruited and divided r and omly into group A and group B -- each consisting of 20 volunteers . The treatment procedure for group A was 500 mg NS capsule twice daily for nine weeks and Group B received placebo instead of NS in the similar manner . All the volunteers were assessed for neuropsychological state and safety profile twice before treatment and after nine weeks . The neuropsychological tests were logical memory test , digit span test , Rey-Osterrieth complex figure test , letter cancellation test , trail making test and stroop test . Safety profile was assessed by measuring biochemical markers of Cardiac ( total cholesterol , triglycerides and high density lipoprotein cholesterol , very low density lipoprotein , low density lipoprotein cholesterol , creatine kinase-MB ) ; Liver ( aspartate aminotransferase , alanin aminotransferase , alkaline phosphatase , total protein , albumin , bilirubin ) and Kidney ( creatinine and blood urea nitrogen ) through using commercial kits . RESULTS There was significant difference ( p<0.05 ) in the score of logical memory test-I and II , total score of digit span , 30 min delayed-recall , percent score in Rey-Osterrieth complex figure test , time taken to complete letter cancellation test , time taken in trail making test-A and test-B , score in part C of stroop test due to ingestion of NS for nine weeks . There were not statistically significant changes ( p>0.05 ) in any of the biochemical markers of cardiac , liver , kidney function during this nine-week study period . CONCLUSIONS The current study demonstrates the role of NS in enhancing memory , attention and cognition . Therefore , whether NS could be considered as potential food supplement for preventing or slow progressing of Alzheimer disease needs further investigations . However , study with Alzheimer 's patients with large population size for longer period of time is recommended before using NS daily and extensive phytochemical investigations are recommended for novel drug discovery from NS for treating cognitive disorders Physical activity has been proposed as one of the most effective strategies to prevent cognitive decline . Protein supplementation may exert an additive effect . The effect of resistance-type exercise training with or without protein supplementation on cognitive functioning in frail and pre-frail elderly people was assessed in a secondary analysis . Two 24-week , double-blind , r and omized , placebo-controlled intervention studies were carried out in parallel . Subjects performed a resistance-type exercise program of two sessions per week ( n=62 ) or no exercise program ( n=65 ) . In both studies , subjects were r and omly allocated to either a protein ( 2 × 15 g daily ) or a placebo drink . Cognitive functioning was assessed with a neuropsychological test battery focusing on the cognitive domains episodic memory , attention and working memory , information processing speed , and executive functioning . In frail and pre-frail elderly , resistance-type exercise training in combination with protein supplementation improved information processing speed ( changes in domain score 0.08±0.51 versus -0.23±0.19 in the non-exercise group , p=0.04 ) . Exercise training without protein supplementation was beneficial for attention and working memory ( changes in domain scores 0.35±0.70 versus -0.12±0.69 in the non-exercise group , p=0.02 ) . There were no significant differences among the intervention groups on the other cognitive tests or domain scores |
13,849 | 12,038,911 | Editorial peer review , although widely used , is largely untested and its effects are uncertain | CONTEXT Editorial peer review is widely used to select su bmi ssions to journals for publication and is presumed to improve their usefulness .
Sufficient research on peer review has been published to consider a synthesis of its effects . | OBJECTIVE To test the hypothesis that there is a review er bias against publication of a test of an unconventional drug . DESIGN R and omized , controlled , double-blind study of peer review . PARTICIPANTS Convenience sample of 291 medical doctors from a wide variety of specialties drawn from a list of conference participants . METHODS Review ers were r and omly assigned to receive one of two versions of a manuscript . Version M related to an in-vitro experiment on a mainstream drug ( Metoprolol ) . The otherwise identical version V used a highly unconventional drug ( beef spleen cell extract ) for the same experiment . Review ers were asked to complete a st and ardised evaluation sheet including visual analogue scales ( VASs ) on a set of predefined quality criteria . All participants were debriefed after completion of the study . RESULTS The response rate was 61 % . There were no significant differences in VAS ratings between the two versions of the manuscript . Ratings covered the entire range of the VASs . CONCLUSION In the present setting , there was no evidence for a review er-bias against testing an unconventional drug . The low inter-rater reliability , however , suggested inadequate validity of peer review Publication of medical research has high stakes : the communication and legitimization of medical research , the advancement of authors ' careers , priorities in funding decisions , the direction of future research , and the visibility and prestige of journals themselves . Peer review and editing play central roles in the publication process , affecting the acceptance of a manuscript and the form in which it appears . The most commonly heard justification of peer review is that it is an indispensable aid to an editor in assessing the importance of a scientific question and in assessing how well that question has been answered [ 1 , 2 ] . However , it has also been criticized as being inherently conservative , censorial , and , perhaps worst of all , arbitrary [ 3 ] . A frequently heard charge is that peer review delays the dissemination of crucial medical information without commensurate benefit [ 4 - 7 ] . During the last several years , some medical journal editors decided that the value of peer- review and editing practice s should be examined with the same rigor dem and ed for testing medical hypotheses [ 8 , 9 ] . The First International Congress on Peer Review was organized in 1989 [ 10 ] , bringing together medical journal editors and other interested scholars to present and discuss research on peer review ; a second Congress was held in 1993 . The peer- review process has two components : the assessment s by external review ers and the decisions and actions taken by editors , which are partially affected by comments from the review ers . To our knowledge , no study has evaluated the effects of peer review and editing on manuscript quality once the decision to accept has been made , and a computerized search of Index Medicus back to 1966 failed to locate any such studies . In this paper , we present the results of such a study , assessing the change in a manuscript between the times of provisional acceptance and final publication . We studied whether the quality of accepted manuscripts was improved by peer- review and editorial processes and , if it was , which aspects were most improved . Methods Setting The study was conducted at the editorial offices of Annals of Internal Medicine . Annals , a specialty journal in internal medicine , is published twice monthly and has a circulation of approximately 100 000 . Annals receives approximately 2400 manuscripts annually , of which half are reports of original research . During the period of this study , the investigators included the editors of Annals ( RHF and SWF ) and a statistical associate editor ( SNG ) . The Review Process No change was noted in the usual review and editing procedures at Annals during the time of this study . All manuscripts received at Annals were initially review ed by one of two full-time editors or one of two half-time deputy editors , as well as by one of seven associate editors , all of whom are faculty members of medical schools in Philadelphia and have subspecialty interests ( for example , infectious disease , gastroenterology ) . Half of the su bmi ssions were returned to authors without further review and half were sent to at least 2 outside review ers , selected by the associate editor from a data base of about 7000 review ers . After comments from the review ers were received , the original editor and associate editor reassessed each manuscript and chose which ones would be discussed at a weekly editorial conference of editors , deputy editors , medical associate editors , and two statistical associate editors . Factors that affected acceptance decisions included the quality of the research , the importance of the question , the contribution of the finding to its field , the utility and interest for Annals readers , the quality of the presentation , the priority relative to other articles , and available space . Authors were notified either that the editors would not accept the paper , that the editors were willing to reconsider the paper after major revisions , or that the paper was provisionally accepted , pending satisfactory revision . Approximately one third of the articles evaluated by outside review ers were accepted , 15 % of su bmi tted original research articles . Papers to be considered further were sent to authors , along with the comments of the two outside review ers , comments of one of the statistical editors , and a letter from one of the editors or deputy editors ( which summarized the discussion at the weekly conference , the ideas of the associate editor , and suggestions from the editor ) . In addition , each manuscript was review ed by a production editor , and directions for changes in manuscript wording or layout of figures and tables were included . All revised manuscripts were review ed by the editor or deputy editor in charge of the manuscript , the appropriate associate editor , the statistical editor , and the production editor . Some revised manuscripts were also reassessed by the original outside review ers . Approximately half of the revised manuscripts were returned to authors for further revision . Most revised manuscripts ( > 95 % ) were ultimately published . The time taken by this process was approximately 2 weeks for the initial decision to review or reject , 8 additional weeks to review and make an acceptance decision , 8 weeks until final acceptance , and about 4 months until publication . More than 95 % of manuscripts su bmi tted to Annals had a provisional acceptance or rejection decision sent to the authors within 3 months . The average time from su bmi ssion to publication was about 7 months , with initial peer review accounting for approximately 6 weeks . Manuscript Selection and Study Design All original research manuscripts ( articles ) accepted for publication by Annals from March 1992 to March 1993 were entered into the study after obtaining the author 's consent . Commentaries , review s , expository pieces , editorials , and brief reports were not included . This study had a beforeafter design , in which two versions of each manuscript were evaluated : the version originally su bmi tted and the version sent to the printer for publication after all modifications based on peer review , editors ' comments , and copyediting . All before and after manuscripts were in electronic form and were reformatted to make the appearance of the two versions identical . Authors ' names and affiliations were removed . The design of the study was approved by the Institutional Review Board of the University of Pennsylvania School of Medicine . Definition of Quality Manuscript quality can be separated conceptually into two components : the quality of the research itself , and the quality of the research report . The quality of the research report was evaluated in this study . It was defined as follows on the cover sheet of the quality assessment instrument : Whether the authors have described their research in enough detail and with sufficient clarity so a reader could make an independent judgment about the strengths and weaknesses of their data and conclusions . Manuscript Quality Assessment Instrument A 34- question instrument was developed to structure the assessment of the quality of a manuscript ( Appendix ) . Items were derived from published checklists [ 11 - 14 ] , articles about the contents of journal articles [ 15 - 18 ] , the authors ' editorial experience , and the comments of journal editors and method ologists who review ed drafts of the instrument . Each question could be answered on a 5-point ordinal scale , where 1 was worst and 5 was best . The instrument was organized along the same dimensions as a st and ard journal article : Title and Abstract ( 2 items ) , Introduction ( 2 items ) , Methods ( 7 items ) , Results ( 15 items ) , Discussion and Conclusions ( 4 items ) , and General Evaluation ( 4 items ) . An additional question asked for a subjective assessment of the manuscript 's overall quality on a 10-point scale . The instrument differed from previously published quality scoring schemes in several ways . It was not a checklist but rather was a set of structured judgments , grade d ordinally , allowing users the discretion not to penalize a manuscript if a detail was omitted that was not critical to the study 's interpretation . Also , in keeping with the definition of quality given above , each question was about the adequacy of the reporting rather than the quality of the research itself . Assessment A panel of 44 physicians and epidemiologists with training in research methods and in critically assessing the medical literature was recruited to serve as an independent panel of expert assessors ( experts ) . They did not receive any formal training in the use of the assessment instrument , although general guidelines were given on the cover sheet ( Appendix ) . The panel was masked to the design and aims of the study ; they were told only that they were participating in a study of manuscript quality for Annals . Before and after versions of each manuscript were r and omly assigned to different experts to prevent the bias that might have been introduced if they could infer the design of the study and thereby which manuscript had been through the editorial process . Thirty-two manuscript versions were given to two or three experts to assess the reliability of the instrument ; all others were assessed by only one expert . Statistical Analyses The study was design ed to have 90 % power to detect a 0.5 unit change in average score , assuming a within-manuscript st and ard deviation of 1 scale unit , using = 0.05 . The main outcome measure was the percentage of items that were scored 3 or higher on the 5-point scales ( percentage score ) . The average of all score components ( average score ) was also analyzed . Linear regression was used to assess the effect of revision on each of these outcome measures , with terms controlling for manuscript and review er . Item-specific analyses were done on dichotomized item scores ( 0 for ratings 2 and 1 for ratings 3 ) . The change from before revision to after revision in individual items was statistically assessed with conditional logistic regression , which allowed for variable group CONTEXT The quality of a process can only be tested against its agreed objectives . Editorial peer- review is widely used , yet there appears to be little agreement about how to measure its effects or processes . METHODS To identify outcome measures used to assess editorial peer review as performed by biomedical journals , we analyzed studies identified from 2 systematic review s that measured the effects of editorial peer review on the quality of the output ( ie , published articles ) or of the process itself ( eg , review ers ' comments ) . RESULTS Ten studies used a variety of instruments to assess the quality of articles that had undergone peer review . Only 1 , nonr and omized study compared the quality of articles published in peer- review ed and non-peer- review ed journals . The others measured the effects of variations in the peer- review process or used a before- and -after design to measure the effects of st and ard peer review on accepted articles . Eighteen studies measured the quality of review ers ' reports under different conditions such as blinding or after training . One study compared the time and cost of different review processes . CONCLUSIONS Until we have properly defined the objectives of peer- review , it will remain almost impossible to assess or improve its effectiveness . The research needed to underst and the broader effects of peer review poses many method ologic problems and would require the cooperation of many parts of the scientific community CONTEXT Anxiety about bias , lack of accountability , and poor quality of peer review has led to questions about the imbalance in anonymity between review ers and authors . OBJECTIVE To evaluate the effect on the quality of peer review of blinding review ers to the authors ' identities and requiring review ers to sign their reports . DESIGN R and omized controlled trial . SETTING A general medical journal . PARTICIPANTS A total of 420 review ers from the journal 's data base . INTERVENTION We modified a paper accepted for publication introducing 8 areas of weakness . Review ers were r and omly allocated to 5 groups . Groups 1 and 2 received manuscripts from which the authors ' names and affiliations had been removed , while groups 3 and 4 were aware of the authors ' identities . Groups 1 and 3 were asked to sign their reports , while groups 2 and 4 were asked to return their reports unsigned . The fifth group was sent the paper in the usual manner of the journal , with authors ' identities revealed and a request to comment anonymously . Group 5 differed from group 4 only in that its members were unaware that they were taking part in a study . MAIN OUTCOME MEASURE The number of weaknesses in the paper that were commented on by the review ers . RESULTS Reports were received from 221 review ers ( 53 % ) . The mean number of weaknesses commented on was 2 ( 1.7 , 2.1 , 1.8 , and 1.9 for groups 1 , 2 , 3 , and 4 and 5 combined , respectively ) . There were no statistically significant differences between groups in their performance . Review ers who were blinded to authors ' dentities were less likely to recommend rejection than those who were aware of the authors ' identities ( odds ratio , 0.5 ; 95 % confidence interval , 0.3 - 1.0 ) . CONCLUSIONS Neither blinding review ers to the authors and origin of the paper nor requiring them to sign their reports had any effect on rate of detection of errors . Such measures are unlikely to improve the quality of peer review reports OBJECTIVE To study whether review ers aware of author identity are biased in favor of authors with more previous publications . DESIGN R and omized controlled trial . SETTING Editorial office of the Journal of Developmental and Behavioral Pediatrics . PARTICIPANTS Two " blinded " and two " nonblinded " review ers assigned to 57 consecutive manuscripts su bmi tted between September 1991 and March 1992 . OUTCOME MEASURES Spearman rank correlation coefficients were used to compare the sum of rating scores of 1 to 5 ( 1 , accept ; 5 , reject ) given by the two blinded review ers , the two nonblinded review ers , and the editors to the number of articles published previously by the first and senior authors ( as determined from requested curricula vitae ) . Blinded review ers were sent a question naire asking whether they could determine the identity of the authors , how they knew , and whether they thought binding changed the quality or difficulty of their review . RESULTS The Wilcoxon Sign Rank Test disclosed no differences between blinded and nonblinded scores . The number of previous articles by the senior author was significantly correlated ( P < .01 ) with blinded scores ( r = -.45 ) and editors ' decisions ( r = -.45 ) , but not with nonblinded scores ; the number of articles by the first author was correlated ( P < .05 ) with editors ' decisions ( r = -.35 ) but not with blinded or nonblinded scores . Fifty ( 46 % ) of 108 blinded review ers correctly guessed the identity of the authors , mostly from self-references and knowledge of the work ; 86 % believed blinding did not change the quality of their review , and 73 % believed it did not change the difficulty of performing a review . CONCLUSIONS Blinded review ers and editors in this study , but not nonblinded review ers , gave better scores to authors with more previous articles . These results suggest that blinded review ers may provide more unbiased review s and that nonblinded review ers may be affected by various types of bias The objectives of this study were to see whether , in the opinion of authors , blinding or unmasking or a combination of the two affects the quality of review s and to compare authors ’ and editors ’ assessment s. In a trial conducted in the British Medical Journal , 527 consecutive manuscripts were r and omized into one of three groups , and each was sent to two review ers , who were r and omized to receive a blinded or an unblinded copy of the manuscript . Review quality was assessed by two editors and the corresponding author . There was no significant difference in assessment between groups or between editors and authors . Review s recommending publication were scored more highly than those recommending rejection CONTEXT All authors may not be equal in the eyes of review ers . Specifically , well-known authors may receive less objective ( poorer quality ) review s. One study at a single journal found a small improvement in review quality when review ers were masked to author identity . OBJECTIVES To determine whether masking review ers to author identity is generally associated with higher quality of review at biomedical journals , and to determine the success of routine masking techniques . DESIGN AND SETTING A r and omized controlled trial performed on external review s of manuscripts su bmi tted to Annals of Emergency Medicine , Annals of Internal Medicine , JAMA , Obstetrics & Gynecology , and Ophthalmology . INTERVENTIONS Two peers review ed each manuscript . In one study arm , both peer review ers received the manuscript according to usual masking practice . In the other arm , one review er was r and omized to receive a manuscript with author identity masked , and the other review er received an unmasked manuscript . MAIN OUTCOME MEASURE Review quality on a 5-point Likert scale as judged by manuscript author and editor . A difference of 0.5 or greater was considered important . RESULTS A total of 118 manuscripts were r and omized , 26 to usual practice and 92 to intervention . In the intervention arm , editor quality assessment was complete for 77 ( 84 % ) of 92 manuscripts . Author quality assessment was complete on 40 ( 54 % ) of 74 manuscripts . Authors and editors perceived no significant difference in quality between masked ( mean difference , 0.1 ; 95 % confidence interval [ CI ] , -0.2 to 0.4 ) and unmasked ( mean difference , -0.1 ; 95 % CI , -0.5 to 0.4 ) review s. We also found no difference in the degree to which the review influenced the editorial decision ( mean difference , -0.1 ; 95 % CI,-0.3 to 0.3 ) . Masking was often unsuccessful ( overall , 68 % successfully masked ; 95 % CI , 58%-77 % ) , although 1 journal had significantly better masking success than others ( 90 % successfully masked ; 95 % CI , 73%-98 % ) . Manuscripts by generally known authors were less likely to be successfully masked ( odds ratio , 0.3 ; 95 % CI , 0.1 - 0.8 ) . When analysis was restricted to manuscripts that were successfully masked , review quality as assessed by editors and authors still did not differ . CONCLUSIONS Masking review ers to author identity as commonly practice d does not improve quality of review s. Since manuscripts of well-known authors are more difficult to mask , and those manuscripts may be more likely to benefit from masking , the inability to mask review ers to the identity of well-known authors may have contributed to the lack of effect Abstract Objectives : To examine the effect on peer review of asking review ers to have their identity revealed to the authors of the paper . Design : R and omised trial . Consecutive eligible papers were sent to two review ers who were r and omised to have their identity revealed to the authors or to remain anonymous . Editors and authors were blind to the intervention . Main outcome measures : The quality of the review s was independently rated by two editors and the corresponding author using a vali date d instrument . Additional outcomes were the time taken to complete the review and the recommendation regarding publication . A question naire survey was undertaken of the authors of a cohort of manuscripts su bmi tted for publication to find out their views on open peer review . Results : Two editors ' assessment s were obtained for 113out of 125manuscripts , and the corresponding author 's assessment was obtained for 105 . Review ers r and omised to be asked to be identified were 12 % ( 95 % confidence interval 0.2 % to 24 % ) more likely to decline to review than review ers r and omised to remain anonymous ( 35 % v 23 % ) . There was no significant difference in quality ( scored on a scale of 1to 5 ) between anonymous review ers ( 3.06(SD 0.72 ) ) and identified review ers ( 3.09(0.68 ) ) ( P=0.68 , 95 % confidence interval for difference −align = baseline>0.19 to 0.12 ) , and no significant difference in the recommendation regarding publication or time taken to review the paper . The editors ' quality score for review s ( 3.05(SD 0.70 ) ) was significantly higher than that of authors ( 2.90(0.87))(P<0.005 , 95%confidence interval for difference − align = baseline>0.26 to − align = baseline>0.03 ) . Most authors were in favour of open peer review . Conclusions : Asking review ers to consent to being identified to the author had no important effect on the quality of the review , the recommendation regarding publication , or the time taken to review , but it significantly increased the likelihood of review ers declining to review Peer review ers are blinded sometimes to authors ' and institutions ' names , but the effects of blinding on review quality are not known . We , therefore , conducted a r and omized trial of blinded peer review . Each of 127 consecutive manuscripts of original research that were su bmi tted to the Journal of General Internal Medicine were sent to two external review ers , one of whom was r and omly selected to receive a manuscript with the authors ' and institutions ' names removed . Review ers were asked , but not required , to sign their review s. Blinding was successful for 73 % of review ers . Quality of review s was higher for the blinded manuscripts ( 3.5 vs 3.1 on a 5-point scale ) . Forty-three percent of review ers signed their review s , and blinding did not affect the proportion who signed . There was no association between signing and quality . Our study shows that , in our setting , blinding improves the quality of review s and that research on the effects of peer review is possible BACKGROUND The quality of peer review ing in developing countries is thought to be poor . To examine whether this was so , we compared the performance of Indian and non-Indian review ers who were sent original and review articles su bmi tted to The National Medical Journal of India . We also tested whether informing review ers that their comments would be exchanged improved the quality of their review s. METHODS In a prospect i ve , r and omized , blinded study , we sent 100 manuscripts to pairs of peer review ers ( Indian and non-Indian ) of which 78 pairs of completed replies were available for analysis . Thirty-eight pairs of review s were exchanged and 40 were not . The quality of the review s was assessed by two editors who were unaware of the review ers ' nationality and whether they had been told that their review s would be exchanged . The quality of the review s was scored out of 100 ( based on a pre design ed evaluation proforma ) . We also measured the time taken to return a manuscript . RESULTS Overall , non-Indian review ers scored higher than Indians ( mean scores non-Indians first , 56.7 v. 48.6 , p < 0.001 ) , especially those in the non-exchanged group ( 58.4 v. 47.3 , p < 0.001 ) but not the exchanged group ( 54.8 v. 50.0 , p < 0.06 ) . Being informed that review s would be exchanged did not affect the quality of review s by non-Indians ( 54.8 exchanged v. 58.4 non-exchanged ) or of review s by Indians ( 50.0 exchanged v. 47.3 non-exchanged ) . The editors ' assessment of the review ers matched well ( r = 0.59 , p < 0.001 ) . Non-Indians took the same amount of time as Indians to return their review s , although the postage time was at least eight days longer . CONCLUSIONS We found that non-Indian peer review ers were better than Indians and informing them that their views would be exchanged did not seem to affect the quality of their review s. We suggest that Indian editors should also use non-Indian review ers and start training programmes to improve the quality of peer review s in India BACKGROUND Academic biomedical journals use peer review and editing to help to select and improve the quality of articles . We have investigated whether articles accepted by the Nederl and s Tijdschrift voor Geneeskunde , the Dutch Journal of Medicine , were improved after peer review and editing ( post-acceptance scientific and copy editing ) . METHODS 400 readers of the journal ( 100 each of medical students , recent medical graduates , general practitioners , and specialists ) were invited to participate in a question naire survey . The first 25 from each group who agreed to participate were included . We posted a pack containing a set of identically appearing typescripts ( ie , blinding ) of the su bmi tted , accepted , and published versions of 50 articles that had been published in Ned Tijdschr Geneeskd . Each evaluator received two of the sets of versions , and each set was evaluated by one person from each group . The package also included two question naires : the first was used to compare the su bmi tted with the accepted version ( 25 questions ) , the second compared the accepted with the published version ( 17 questions ) . The questions were answered on five-point scales , and were about the quality of the articles or were general/overall scores . We analysed the data as scores of 3 - 5 ( ie , improvement ) versus 1 - 2 . FINDINGS After peer review , the quality in 14 of 23 questions ( 61 % ) was significantly improved ( p = 0.03 or smaller ) . In particular , the overall score and general medical value were significantly improved ( p = 0.00001 for each ) . Editing led to significant improvement in 11 of 16 questions ( 69 % , p = 0.017 or smaller ) , and especially in style and readability ( p = 0.001 and p = 0.004 ) . Generally , we found no differences between the scores of the four categories of evaluators . 72 % of the evaluators correctly identified which version was which . INTERPRETATION Evaluations by readers of the Ned Tijdschr Geneeskd indicated significant improvement of published articles after both peer review and editing . We think that peer review and editing are worthwhile tasks . We also think that possible biases would have had a negligible effect on our results ( including the fact that we selected the first 25 evaluators who responded , that some evaluators may have read the published version , and that one question naire may have looked more scientific than the other , more editorial one ) |
13,850 | 24,990,344 | CONCLUSIONS Limited data from two studies suggest that support groups may be of psychological benefit to people with dementia by reducing depression and improving quality of life and self-esteem . | OBJECTIVES Despite the large number of studies evaluating social support groups for people with dementia , there are no systematic review s of current evidence .
The aim of this study was to evaluate the effectiveness of social support group interventions for people with dementia and mild cognitive impairment . | BACKGROUND Subjects with a mild cognitive impairment ( MCI ) have a memory impairment beyond that expected for age and education yet are not demented . These subjects are becoming the focus of many prediction studies and early intervention trials . OBJECTIVE To characterize clinical ly subjects with MCI cross-sectionally and longitudinally . DESIGN A prospect i ve , longitudinal inception cohort . SETTING General community clinic . PARTICIPANTS A sample of 76 consecutively evaluated subjects with MCI were compared with 234 healthy control subjects and 106 patients with mild Alzheimer disease ( AD ) , all from a community setting as part of the Mayo Clinic Alzheimer 's Disease Center/Alzheimer 's Disease Patient Registry , Rochester , Minn. MAIN OUTCOME MEASURES The 3 groups of individuals were compared on demographic factors and measures of cognitive function including the Mini-Mental State Examination , Wechsler Adult Intelligence Scale-Revised , Wechsler Memory Scale-Revised , Dementia Rating Scale , Free and Cued Selective Reminding Test , and Auditory Verbal Learning Test . Clinical classifications of dementia and AD were determined according to the Diagnostic and Statistical Manual of Mental Disorders , Revised Third Edition and the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer 's Disease and Related Disorders Association criteria , respectively . RESULTS The primary distinction between control subjects and subjects with MCI was in the area of memory , while other cognitive functions were comparable . However , when the subjects with MCI were compared with the patients with very mild AD , memory performance was similar , but patients with AD were more impaired in other cognitive domains as well . Longitudinal performance demonstrated that the subjects with MCI declined at a rate greater than that of the controls but less rapidly than the patients with mild AD . CONCLUSIONS Patients who meet the criteria for MCI can be differentiated from healthy control subjects and those with very mild AD . They appear to constitute a clinical entity that can be characterized for treatment interventions One of the defining differences between mild cognitive impairment ( MCI ) and dementia is the degree of independence in everyday activities . Effecting memory-related behavioural change in MCI could help maintain daily function and prolong the time before onset of dependency . However , it is well known that changing previously well-established behaviours is difficult to achieve . We conducted a r and omised controlled trial to evaluate the effectiveness of a multidisciplinary group-based intervention programme in changing everyday memory behaviour in individuals with amnestic MCI . The intervention provided evidence d-based memory training and lifestyle education to optimise memory behaviour . Fifty-four participants were r and omly assigned to treatment or waitlist-control conditions . Consistent with our primary goal , treatment participants showed an increase in memory- strategy knowledge and use from pre-test to immediate post-test , and these gains were maintained at three-month post-test relative to waitlist controls . There were no group differences in memory beliefs or on laboratory tests of objective memory performance . The increase in memory- strategy knowledge and use was associated with the degree of participation in the programme . Individuals with MCI , therefore , can acquire and maintain knowledge about memory strategies and , importantly , can change their everyday memory behaviour by putting this knowledge into practice . This incorporation of practical memory strategies into daily routines could potentially provide the means for maintaining functional independence by individuals with MCI , an issue to be addressed in future research OBJECTIVES This article describes results of a r and omized controlled trial comparing a time-limited early-stage memory loss ( ESML ) support group program conducted by a local Alzheimer 's Association chapter to a wait-list ( WL ) control condition . METHODS One hundred and forty-two dyads were r and omized in blocks to ESML ( n = 96 ) or WL ( n = 46 ) . Mean age of participants was 74.9 years , and mean Mini-Mental State Examination was 23.4 . The primary outcome was participant 's quality of life ; secondary outcomes included mood , family communication , and perceived stress . RESULTS On the intent-to-treat ( ITT ) pre-post analysis , significant differences were seen in participant quality of life ( p < .001 ) , depression ( p < .01 ) , and family communication ( p < .05 ) . Within the care partner groups , there was no significant difference between ESML and WL in the ITT analysis . A post hoc exploratory examination of changes that were associated with improved quality of life in ESML participants revealed significant reductions of depressive symptoms and behavior problems ( p < .05 ) , improved family communication ( p < .05 ) , self-efficacy ( p < .01 ) , Medical Outcomes Study short form ( SF-36 ) role-emotional ( p < .05 ) , SF-36 social functioning ( p < .05 ) , and SF-36 mental health components ( p < .01 ) in improvers . DISCUSSION These results support the efficacy of ESML support groups for individuals with dementia Background : Patients with mild cognitive impairment ( MCI ) have to deal with an uncertain prognosis and also face a multitude of memory-related problems and psychosocial consequences . A newly developed group programme proved to be feasible , however , it needed confirmation by a controlled study . Aim : This controlled study evaluates this group therapy for MCI patients aim ed to help them accept and manage the memory problems and the psychosocial consequences . The programme combines elements from psychoeducation , cognitive rehabilitation and cognitive-behavioural therapy . Patients and Methods : Ninety-three MCI patients received treatment , with 30 patients being first assigned to a waiting list , thus serving as their own control group . Pre- and post-treatment acceptance and helplessness were assessed using subscales of the Illness Cognition Question naire , while distress and general well-being were gauged with the Geriatric Depression Scale and subscales of the R AND -36 . Results : Linear mixed model analyses showed that , relative to the controls , acceptance had increased more in the intervention group compared to the waiting-list period ( p = 0.034 ) . Distress and general well-being showed no changes . Treatment responders demonstrating a clinical ly significant effect on acceptance and two of three secondary outcome measures had higher baseline levels of helplessness and fewer self-reported memory complaints in daily life than patients who did not improve . Conclusion : The intervention helped the patients deal better with their uncertain future in that they were overall better able to accept their condition , with especially the female patients showing a decrease in helplessness cognitions , although the effects were relatively small Objectives : The Enriched Opportunities Programme ( EOP ) is a multi-level intervention focussing on improved quality of life for people with dementia . This study compared the experience of people living with dementia and other mental health problems in extra care housing schemes that utilised EOP with schemes that employed an active control intervention . Method : Ten extra care housing schemes were cluster r and omised to receive either the EOP intervention or an active control intervention for an 18-month period . Residents with dementia or other significant mental health problems ( 20–30 per scheme ) were assessed on a number of outcome measures at baseline , six months , one year and 18 months . The primary outcome measure was quality of life . Self-reported depression was an important secondary outcome . Results : The EOP-participating residents rated their quality of life more positively over time ( 4.0 ( SE 0.6 ) units ; 14 % p < 0.001 ) than the active control ( 1.3 ( SE 0.6 ) units ; 4 % p = 0.003 ) . There was also a significant group – time interaction for depressive symptoms ( p = 0.003 ) . The EOP-participating residents reported a reduction of 25 % at both six and 12 months and a 37 % reduction at 18 months ( all p 's < 0.001 ) . EOP residents were less likely than residents in the active control sites to move to a care home or to be admitted to a hospital inpatient bed . They were more likely to be seen by a range of community health professionals . Conclusion : The EOP had a positive impact on the quality of life of people with dementia in well-staffed extra care housing schemes Background After diagnosis of a dementing illness , patients and their spouses have many concerns related to the disease and their future . This often leads to poor psychological well-being and reduced health-related quality of life ( HRQoL ) of the family . Support for self-management skills has been proven to be an effective method to improve prognosis of asthma , heart failure and osteoarthritis . However , self-management interventions have not been studied in dementia . Therefore , our aim was to examine , in an objective -oriented group intervention , the efficacy of self-management support program ( SMP ) on the HRQoL of dementia patients and their spousal caregivers as well as on the sense of competence and psychological well-being of caregivers . Methods During the years 2011 to 12 , 160 dementia patients and their spouses will be recruited from memory clinics and r and omized into two arms : 80 patients for group-based SMP sessions including topics selected by the participants , 80 patients will serve as controls in usual community care . Sessions may include topics on dementia , community services , active lifestyle and prevention for cognitive decline , spousal relationship , future planning and emotional well-being . The patients and spouses will have their separate group sessions ( ten participants per group ) once a week for eight weeks . Main outcome measures will be patients ’ HRQoL ( 15D ) and spousal caregivers ’ HRQoL ( R AND -36 ) , and sense of competence ( SCQ ) . Secondary measures will be caregivers ’ psychological well-being ( GHQ-12 ) and coping re sources , patients ’ depression , cognition and signs of frailty . Data concerning admissions to institutional care and the use and costs of health and social services will be collected during a two-year follow-up . Discussion This is a ‘ proof-of-concept ’ study to explore the efficacy of group support for self-management skills among dementia families . It will also provide data on cost-effectiveness of the intervention . Trial registration Background Social support is important in daily activities of the elderly . This study tests the hypothesis that there is an association between social support and cognitive function among the elderly in a community setting . Methods Face-to-face interviews were conducted in a cross-sectional stratified r and om sample of 4,993 elderly ( ≥65 years ) city residents . Using multiple regression analysis , we investigated the influence of social support on cognitive function . Results 12 % were over 80 years old . 53.28 % were men . 67.14 % were married . Higher Short Portable Mental Status Question naire ( SPMSQ ) scores ( higher score means better cognitive function ) were associated with strong social support , as measured by marital status and perceived positive support from friends . Lower cognitive function was associated with older and with female respondents . Only instrumental activities of daily living ( IADL ) were statistically and negatively related to SPMSQ . Lower functional status was associated with lower cognitive function . Elders with grade school educations had lower SPMSQ scores than did elders with high school educations . Conclusions In Taiwan , higher cognitive function in community-living elderly was associated with increased social support . Life-style management should provide social activities for the elderly to promote a better quality of life BACKGROUND Relatives and caregivers of patients with dementia are often insecure about the impact of their efforts . This study examines whether and to what extent social support in the form of regular visits is increasing the well-being of demented aged . PROCEDURE A field experiment with slightly to seriously demented institutionalized aged persons ( MMS 5 - 25 ) was carried out to assess the effect of increased social support upon their well-being . Voluntary helpers , who were willing to visit their patients on a regular basis , were recruited by appeals at the senior university and by advertisements . The volunteers were trained to deal with the demented and were looked after regularly . The test subjects were r and omly assigned to one of two test groups . The first group was visited regularly for ten weeks , whereas the second group served as a control group . The participants of the experimental group received a visiting card with a photo of the volunteer and the next appointment date to remember their visitors and to increase the effect of predictability . RESULTS The effect of visits on the well-being of the institutionalized aged persons was significantly positive ( F(1,39 ) = 11.16 , p < 0.002 ) . The psychological , physiological and social well-being of the participants was improved . Additionally , visits moderated the pain result ing from physical illness and seemed to decrease the effects of mental decline on their performance . Furthermore , it was most impressive to find that the demented aged really took notice of the visits and seemed to remember them in one way or an other . The study pointed out that demented aged persons are still very sensitive in an emotional respect and that they are still able to give astonishing good and differentiated information about their feelings even in an advanced state of dementia . Even the volunteers gained from their visits , which was shown by their higher well-being after their visits Accurate clinical staging of dementia in older subjects has not previously been achieved despite the use of such methods as psychometric testing , behavioural rating , and various combinations of simpler psychometric and behavioural evaluations . The Clinical Dementia Rating ( CRD ) , a global rating device , was developed for a prospect i ve study of mild senile dementia -- Alzheimer type ( SDAT ) . Reliability , validity , and correlational data are discussed . The CRD was found to distinguish unambiguously among older subjects with a wide range of cognitive function , from healthy to severely impaired OBJECTIVES To determine whether community care of demented patients can be prolonged by means of a 2-year support program based on nurse case management . DESIGN R and omized controlled intervention study with 2-year follow-up . SETTING Demented patients entitled to payments from the Social Insurance Institution for community care , in five municipalities in eastern Finl and . PARTICIPANTS One hundred demented patients , age 65 and older , living at home with the primary support of informal caregivers , allocated at r and om to the intervention ( n = 53 ) or control group ( n = 47 ) . INTERVENTION Intervention patients and their caregivers were provided with a 2-year intervention program of systematic , comprehensive support by a dementia family care coordinator . MEASUREMENTS Time to institutionalization ( period in community care ) from enrollment of patients in the study to their placement in long-term institutional care . RESULTS During the first months , the rate of institutionalization was significantly lower in the intervention group than in the control group ( P = .042 ) , but the benefit of the intervention decreased with time ( P = .028 ) . Estimated probability of staying in community care up to 6 , 12 , and 24 months was 0.98 , 0.92 , and 0.63 in the intervention group and 0.91 , 0.81 , and 0.68 in the control group , respectively . Results also suggest that the intervention used in the study might be especially beneficial to patients with severe dementia and those with problems threatening the continuity of community care . CONCLUSIONS The placement of demented patients in long-term institutional care can be deferred with the support of a dementia family care coordinator . However , by the end of the 2-year intervention , the number of patients institutionalized was similar in the intervention and control group . It seems to be beneficial to direct this type of intensive support at severely demented patients and their caregivers . On the basis of our experiences , we suggest that intervention by a dementia family care coordinator should be targeted especially at patients with problems threatening the continuity of community care Theories supporting the existence of a use-dependent neuroplasticity in the older brain were used to guide this pilot study . A repeated- measures r and omized design was used to test the effectiveness of a multimodal ( Taiji exercises , cognitive-behavioral therapies , support group ) intervention on cognitive functioning , physical functioning , and behavioral outcomes in persons with dementia . The treatment group ( n = 24 persons with dementia ) participated in a 40-week intervention , with outcomes assessed at 20 and 40 weeks to assess optimal treatment length . Control group subjects ( n = 19 persons with dementia ) received attention-control educational programs . At 20 weeks , differences between groups were found for mental ability and self-esteem , with gains in balance being evident . Also , stability in depression and physical health were evident at 20 and 40 weeks for treatment group subjects . Continued improvement in outcomes was not observed at 40 weeks . However , findings support further testing of the intervention along with potential for achieving positive outcomes in early-stage dementia |
13,851 | 16,187,468 | EMLA may be an effective , noninvasive means of analgesia before dermal procedures .
However , we identified 3 topical anesthetics that are at least as efficacious as EMLA : tetracaine , liposome-encapsulated tetracaine , and liposome-encapsulated lidocaine .
Liposomal lidocaine is commercially available in the United States and offers a more rapid onset and less expensive alternative to EMLA | STUDY OBJECTIVE We compare the analgesic efficacy of topical anesthetics for dermal instrumentation with conventional infiltrated local anesthesia and also compare topically available amide and ester agents with a eutectic mixture of local anesthetics ( EMLA ) . | We have evaluated the anaesthetic effect of tetracaine gel 1 g , applied for 45 min , compared with EMLA cream 2 g , applied for 60 min , in a r and omized , double-blind study in 60 children aged 3 - 15 yr . Venous cannulation was performed 15 min after removal of the EMLA cream ( n = 20 ) and tetracaine gel ( n = 20 ) . Cannulation was performed up to 215 min after removal of the tetracaine gel in another 20 patients . Significantly lower pain scores were recorded by the children treated with tetracaine gel compared with EMLA cream ( P < 0.02 ) . Forty to 45 % of children in the tetracaine groups reported no pain compared with only 10 % in the EMLA group . Only minor adverse effects were observed . We conclude that tetracaine gel provided effective , rapid , long-lasting and safe local anaesthesia , and was significantly better than EMLA cream in reducing pain during venous cannulation in children using the recommended application periods for both formulations OBJECTIVES Children view needle sticks as the worst source of pain and fear in the hospital setting . In an effort to minimize the pain of needle sticks , the use of eutectic mixture of lidocaine and prilocaine ( EMLA ) has become st and ard practice in many children 's hospitals . Unfortunately , EMLA requires at least 60 minutes to be fully effective and reportedly may cause vasoconstriction , leading to difficult vein cannulation . A newly available local anesthetic ( ELA-Max ) may require less time and cause less vasoconstriction . The purpose of this r and omized crossover study was to investigate the anesthetic equivalence of EMLA and ELA-Max . METHODS Thirty well children ( 14 girls and 16 boys ) who were between the ages of 7 and 13 years volunteered to have EMLA applied to the dorsal aspect of 1 h and for 60 minutes and ELA-Max applied to the other h and for 30 minutes . Right and left h and s were r and omized to treatment type and order of intravenous ( IV ) insertion . Clinical Research Center nurses , blind to the anesthetic r and omization , attempted to insert a 22-gauge Teflon IV catheter into a vein in each h and . The children rated pain during IV insertion on the Oucher scale , and the nurse rated the difficulty of the insertion . RESULTS There was no significant difference in pain ratings for h and s that were treated with EMLA ( mean : 20.5 ) or with ELA-Max ( mean : 24 ) , and there was no difference for the difficulty of vein cannulation . Children 's preprocedure state anxiety was positively associated with pain ratings . CONCLUSIONS ELA-Max , applied for 30 minutes before IV cannulation , has an anesthetic effectiveness similar to EMLA applied for 60 minutes . Some children rated IV insertion pain fairly high for both h and s ( eg , 60 on a 0- to 100-point scale ) despite anesthetic treatment . Preprocedural anxiety may affect the perception and /or rating of pain . There were no differences between h and s that were treated with EMLA or with ELA-Max for success of IV insertion background . Liposomes are microscopic phospholipid vessels that have been utilized to extend the action of topical medications . Previous studies have demonstrated that liposomal vehicles can prolong the action of a variety of medications , including antifungals , anesthetics , interferon , and antineoplastic agents . objective . The purpose of this study was to examine the degree and duration of anesthesia produced by lidocaine in a liposomal vehicle compared with lidocaine in a nonliposomal vehicle and compared with EMLA . The topical preparations in this study were allowed to contact the skin for a 30‐minute period prior to evaluation of anesthetic effectiveness . Unoccluded and Tegaderm‐occluded topical preparations were evaluated in two separate arms of the study . material s and methods . Thirteen healthy volunteers ( three male , 10 female ) were recruited for the nonocclusion arm of the study . Six healthy volunteers ( two male , four female ) were recruited for the occlusion arm of the study . Subjects with a history of allergy to lidocaine , a history of seizures , cardiac or respiratory difficulty , pregnant patients , and patients less than 18 years old were excluded . Written informed consent was obtained from all patients prior to testing . The volar forearms of the volunteers were swabbed with isopropyl alcohol and allowed to dry . A template was then utilized to mark 2 × 2‐cm squares with a skin marker on both volar forearms . In total , nine squares corresponding to nine test areas were marked . The nine test preparations were applied to the test areas in a double‐blinded fashion using a clean swab stick . The test preparations were then allowed to remain on the skin for 30 minutes in either occluded or nonoccluded form depending upon the arm of the study . Following the 30‐minute application period , the test preparations were wiped off with clean gauze . Testing for anesthesia was performed by following a previously published method utilizing gentle pinpricks . A new pinprick apparatus was used for each patient . Pinprick testing was performed at 0 , 15 , 30 , 60 , and 90 minutes following the end of the 30‐minute application period . Patients ' responses to the pinprick were recorded in a binary fashion , as being either : 1 ) totally painless or 0 ) painfully sharp to any degree . Ten applications of the pinprick were applied r and omly across each 2 × 2‐cm test area . The number of painless applications of the pinprick out of a total of 10 applications of the pinprick was then recorded for each test area at every particular test time . In total , nine test preparations were evaluated . Analysis of the data was performed by a PhD statistical faculty consultant from the UCLA Mathematics Department . results . Liposomal lidocaine preparations evidence d longer duration s of anesthesia than lidocaine preparations in nonliposomal vehicles . Five percent liposomal lidocaine preparations were statistically equivalent to EMLA in anesthetic effectiveness . conclusion . Five percent liposomal lidocaine is an effective alternative topical agent for use in the attainment of temporary local anesthesia of the skin A r and omized double-blind study was conducted in 83 women scheduled for elective caesarean section to determine the efficacy of EMLA and lignocaine infiltration for epidural insertion . The patients were r and omly allocated to one of three groups : Group A ( EM/LIG ) received EMLA and intradermal and subdermal 1 % lignocaine infiltration , Group B ( EM/SAL ) EMLA and saline while Group C ( PL/LIG ) received placebo cream and 1 % lignocaine . Assessment s using a 100 mm pain score were performed on skin infiltration and after subsequent insertion of a 16 gauge Tuohy needle into the supraspinous ligament . Skin changes under the applied cream and nursing rating of patients ’ response were also noted . Statistical analyses were performed using Kruskal-Wallis and Fisher 's Exact Tests . Groups were comparable for age , weight , parity and EMLA application time ( interquartile range 105 - 150 minutes ) There were significantly higher pain scores for skin infiltration in Group C ( PL/LIG ) ( P<0.01 ) and for epidural needle insertion in Group B ( EM/SAL ) ( P<0.05 ) . We concluded that in this patient population , the application of EMLA cream for at least 90 minutes plus 1 % lignocaine infiltration optimized patient comfort for epidural insertion Background The eutectic mixture of local anaesthetics ( EMLA ) provides effective topical anaesthesia after a minimum of 60 to 90 mm application . Since liposome-encapsulated tetracaine ( LET ) can provide rapid dermal penetration , the goal of this study was to compare the local anaesthetic effects of EMLA and LET in human volunteers after 60 mm application . Methods After obtaining institutional approval and informed consent , healthy volunteers were recruited in a double blind , crossover , r and omized trial . The study creams ( 0.5 ml EMLA and 0.5 ml LET 5 % ) were applied r and omly to opposite arms for 60 min . The discomfort of iv cathetenzation was assessed using a visual analogue pain score ( VAS ) . Cutaneous side effects of the creams were recorded . Results Sixty-one subjects were studied . Twenty-one were excluded because of technical difficulties . Forty subjects completed the study and were included in the data analysis . The mean ( ±SD ) VAS was lower for LET than for EMLA ( 10.9 ± 9.0 mm vs 22.7 ± 17.1 mm , P < 0.001 ) . Erythema secondary to vasodilatation occurred more frequent in the LET group than in the EMLA group ( 33 vs 3 . P < 0.001 ) . One subject with a history of atopy developed a rash at the LET application site . Conclusion Liposome-encapsulated tetracaine can provide a more effective topical anaesthesia than EMLA for intravenous catheterization after 60 min application . Clinical evaluations are necessary to determine the efficacy and safety of LET in providing topical anaesthesia for vanous invasive percutaneous procedures in other patient population s . RésuméObjectifLe mélange eutectique d’anesthésique local ( EMLA ) appliqué pendant 60 à 90 minutes procure une anesthésie topique efficace . On sait que tétracaïne encapsulée dans les liposomes ( LET ) pénètre le derme rapidement . Cette étude a été entreprise pour comparer les effets anesthésiques locaux de l’EMLA et du LET chez des volontaires humains après 60 mm d’application . MéthodesAprès obtention de l’approbation des instances appropriées et du consentement éclairé , des volontaires ont été recrutés dans une étude aléatoire croisée à double insu . Les crèmes ( EMLA 0.5 ml et LET 5 % 0,5 ml ) ont été appliquées aléatoirement sur des bras opposés pendant 60 min . L’inconfort de la canulation veineuse a été évalué sur une échelle visuelle analogique ( ÉVA ) . Les effets secondaires ont été notés . RésultatsSoixante et un sujets ont participé à l’étude do nt vingt et un ont été rejetés à cause de problèmes techniques . Quarante sujets ont complété l’étude et ont été conservés pour l’analyse des données . L’ÉVA moyenne ( ±ÉT ) du LET était inférieure à celle de l’EMLA ( 10.9 ± 9.0 mm vs 22,7 ± 17.1 . P < 0,001 ) . L’érythème secondaire à la vasodilatation était plus fréquent dans le groupe LET que dans le groupe EMLA ( 33 vs 3 , P < 0.001 ) . Un des sujets considéré comine atopique a présenté de l’érythème au site d’application du LET . Conclusion La tétracaïne encapsulée dans les liposomes peut procurer une anesthésie topique plus efficace que l’EMLA pour la canulation veineuse après 60 min d’application . Des évaluations cliniques sont nécessaires pour déterminer l’efficacité et l’innocuité du LET pour l’anesthésie topique pendant des manipulations percutanées diverses chez d’autres groupes de patients In a double-blind , double-dummy study , the efficacy of topical 5 % EMLA cream was compared with that of lignocaine infiltration in alleviating the pain of arterial cannulation . Forty unpremedicated adults were allocated r and omly to four groups to receive EMLA cream alone , EMLA and 0.9 % saline infiltration , EMLA and 1 % lignocaine infiltration or placebo cream and 1 % lignocaine infiltration . Following arterial cannulation , pain was assessed by the patient using a visual analogue score and by an independent observer using a four-category verbal rating score . Significantly lower pain scores were observed in all patients receiving EMLA compared with those receiving placebo cream and lignocaine infiltration by both patient ( P less than 0.01 ) and observer ( P less than 0.001 ) assessment s. There were no significant differences between the three EMLA groups In this r and omized , double-blind study , we have compared the ability of 5 % liposome-encapsulated tetracaine ( amethocaine ) ( LET ) vs 5 % eutectic mixture of local anaesthetics ( EMLA ) to produce local anaesthesia of intact skin in 40 healthy volunteers . Volunteers had both preparations applied to their forearms under an occlusive dressing for 1 h. Superficial anaesthesia was measured by a total of nine 1-mm pinpricks on each arm . Deeper anaesthesia was assessed by single insertion of a sterile 22-gauge needle to a depth of 3 mm and pain was reported on a visual analogue scale ( VAS ) . If the volunteer perceived greater than four of the 1-mm pinpricks , the 3-mm insertion was not performed . Results showed that the number of pinpricks perceived was significantly less ( P < 0.01 ) for LET ( median 1.0 ; range 0 - 9 ) vs EMLA ( 1.5 ; 0 - 9 ) . In volunteers who had deeper anaesthesia assessed , there was no significant difference ( P = 0.065 ) in VAS scores for LET ( mean 1.5 ( SD 1.4 ) ; n = 34 ) vs EMLA ( 2.4 ( 2.1 ) ; n = 28 ) . Overall anaesthetic effect , as ranked by all of the subjects , was significantly better for LET compared with EMLA ( P = 0.024 ) . We have demonstrated that when applied in equal volumes , 5 % LET produced better superficial local anaesthesia than EMLA OBJECTIVES To determine the minimum clinical ly significant difference in visual analog scale ( VAS ) pain scores for acute pain in the ED setting and to determine whether this difference varies with gender , age , or cause of pain . METHODS A prospect i ve , descriptive study of 152 adult patients presenting to the ED with acute pain . At presentation and at 20-minute intervals to a maximum of three measurements , patients marked the level of their pain on a 100-mm , nonhatched VAS . At each follow-up they also gave a verbal rating of their pain as " a lot better , " " much the same , " " a little worse , " or " much worse . " The minimum clinical ly significant difference in VAS pain scores was defined as the mean difference between current and preceding scores when pain was reported as a little worse or a little better . Data were compared based on gender , age more than or less than 50 years , and traumatic vs nontraumatic causes of pain . RESULTS The minimum clinical ly significant difference in VAS pain scores is 9 mm ( 95 % CI , 6 to 13 mm ) . There is no statistically significant difference between the minimum clinical ly significant differences in VAS pain scores based on gender ( p=0.172 ) , age ( p=0.782 ) , or cause of pain ( p=0.84 ) . CONCLUSIONS The minimum clinical ly significant difference in VAS pain scores was found to be 9 mm . Differences of less than this amount , even if statistically significant , are unlikely to be of clinical significance . No significant difference in minimum significant VAS scores was found between gender , age , and cause-of-pain groups We have compared , in a double-blind study , the efficacy of topical amethocaine cream 1 g ( 5 % w/w ) in alleviating the pain of venous cannulation with that of 5 % EMLA cream 2.5 g. One hundred and twenty unpremedicated female patients undergoing minor gynaecological surgery , were allocated r and omly to one of four groups : 5 % EMLA cream 2.5 g for 30 min : 5 % EMLA cream 2.5 g for 60 min ; amethocaine cream 1 g ( 5 % w/w ) for 30 min ; amethocaine cream 1 g ( 5 % w/w ) for 60 min . After removal of the cream , venous cannulation was performed with an 18-gauge cannula . Patients assessed the pain experienced using a 100-mm visual analogue score and four-point rank score . In addition , a blinded observer assessed the patient 's response to venous cannulation using a four-point rank score . Good analgesia was obtained in all groups and there was no statistically significant difference in pain scores between the groups The efficacy of the use of EMLA cream to provide skin anaesthesia prior to the insertion of 16 G Tuohy needles was assessed . Sixty women in labour were r and omly allocated to receive either EMLA cream over the proposed epidural site for a minimum period of 5 min ( mean 9.1 min ) , a skin bleb and subcutaneous injection oflignocaine 2 % ( 1 ml ) , or a skin bleb with additional lignocaine 2 % ( 2 ml ) infiltrated into the supra and interspinous ligaments using a 23 G needle . Once the epidural catheter was sited , using a st and ard technique , 10 cm visual analogue pain scales were completed independently by the patient , by a blinded midwife and by the anaesthetist siting the epidural . Patients ' perception of pain was not significantly different in any of the three groups , although the mean pain score was least in the group receiving full infiltration . The anaesthetists consistently underestimated the patients ' perception of pain Background and Objectives The study was design ed to compare the analgesic efficacy of the local anesthetic EMLA when applied as a patch and as a cream in combination with a Tegaderm dressing to pediatric oncology patients undergoing repeated lumbar punctures . Methods The analgesic effect of the two products was assessed by a continuous or discrete visual analog scale in 24 children 3 - 16 years old , during two lumbar punctures . Distress was rated by use of the Observational Scale of Behavioral Distress . Results No significant differences were found between the pain and distress scores for the different preparations of EMLA . Conclusion The EMLA patch and the EMLA cream are equally effective in alleviating pain associated with lumbar puncture . The EMLA patch simplifies and speeds up the application of EMLA . It also allows for control of the dose administered per application , thus preventing both over- and underdosing Three commonly available local anaesthetics were compared , in a controlled trial , for use before venous cannulation . The pain of application of the local anaesthetic , the pain of cannulation , and the rate of successful cannulations were compared . The value of EMLA cream applied for 5 min was question ed . Venous cannulation with a 20 G venflon was found to be significantly more painful than the application of any of the local anaesthetics ( P < 0.01 ) . Lignocaine 1 % , injected subcutaneously , and ethyl chloride spray significantly reduced the pain of venous cannulation ( P < 0.01 ) . The use of lignocaine did not result in significantly more failed cannulations than the control group . It was concluded that local anaesthesia should be used before venous cannulation , even for 20 G cannulae The efficacy of tetracaine cream versus that of lidocaine-prilocaine cream for the prevention of pain in children undergoing venipuncture was studied . Hospital in patients 1 - 15 years of age received , on the back of each h and , a 30-minute application of tetracaine 4 % cream or a 60-minute application of lidocaine-prilocaine cream ( EMLA , Astra ) before undergoing scheduled venipuncture . The phlebotomists in this open , r and omized trial evaluated the efficacy of the cream at the moment of venipuncture as adequate , inadequate , or inconclusive . Blood sample s were taken immediately after venipuncture from 10 patients one to five years of age to measure the serum concentrations of tetracaine and its metabolite , N-butyl-p-aminobenzoic acid . Lidocaine-prilocaine cream was significantly more efficacious in preventing pain than tetracaine 4 % cream ( 97 % of the former group [ n = 32 ] had adequate pain relief , compared with 76 % of the latter [ n = 34 ] . The only adverse effects observed were mild local erythema in the tetracaine group and local skin blanching in the lidocaine-prilocaine group . No tetracaine could be detected in serum , and the serum concentrations of N-butyl-p-aminobenzoic acid ranged from 0 to 1.8 mg/l . Statistically , lidocaine-prilocaine cream was more efficacious than tetracaine 4 % cream , but the difference is of minor clinical significance and is outweighed by the practical advantages of tetracaine 4 % cream , namely the shorter application time , vasodilation and lower cost Objectives To compare the effect of topical skin anaesthetic agents on the discomfort and anxiety associated with venous cannulation . Design R and omised , double-blind , placebo-controlled , within subject , volunteer trial . Methods 20 healthy volunteers underwent venous cannulation on three separate occasions having received topical skin application of either 4 % amethocaine gel ( Ametop ) , 5 % eutectic mixture of lidocaine and prilocaine ( EMLA ) or E45 cream ( placebo ) . Visual analogue and verbal rating scales were used to assess pain and anxiety associated with the venous cannulation , and anticipated anxiety for future cannulation , under each drug condition . Results Subjects were aged 22 - 53 years ( mean 32.8 years ) . The mean visual analogue scores ( VAS ) for discomfort were found to be significantly lower ( p<0.001 ) with Ametop ( VAS = 18 mm ) and EMLA ( VAS = 29 mm ) compared with the control ( VAS = 38 mm ) . There was a positive correlation ( R2 = 72 % , p<0.001 ) between discomfort and the predicted anxiety if cannulation was to be repeated with the same cream . With the placebo a positive correlation ( R2 = 19.8 % , p = 0.05 ) was found between the level of anxiety before cannulation and the level of discomfort recorded . Conclusions Ametop and EMLA topical anaesthetic agents produce effective skin analgesia for venous cannulation . The use of topical analgesia can reduce perceived anxiety about future cannulation procedures . This has application in the management of anxious patients undergoing intravenous sedation , suggesting that topical analgesia prior to venous cannulation may significantly aid anxiolysis The skin application of EMLA cream under a Tegaderm dressing was compared in children with a new combined dressing/local anaesthetic patch — the EMLA patch . The analgesic effect during venepuncture was assessed using a visual analogue scale ( patients ) and a verbal rating scale ( investigator ) . Skin adhesiveness and incidence of local skin reactions with the two types of application were also studied . The study was design ed as an open r and omised trial with two parallel groups . Sixty children , aged between 5 and 15 years were evaluated . After a minimum application time of 60 min an intravenous cannula was inserted . There was no difference in analgesia as assessed by the patients or the investigators . Mild discomfort at removal of the occlusive dressing/patch was observed in a few patients , but there was no difference in the adhesiveness of the Tegaderm dressing and the EMLA patch . Only mild local skin reactions ( with paleness in the anaesthetised skin area ) were observed in both groups . It was concluded that both the EMLA patch and the Tegaderm/EMLA cream dressing provide effective dermal analgesia for venepuncture with a 0.8 mm ( outer diameter ) cannula . The two types of application were indistinguishable but the ease of application of the patch is a distinct advantage Purpose A eutectic mixture of local anesthetics ( EMLA ) is commonly used to provide topical anesthesia for intravenous ( iv ) cannulation . One of its side effects is vasoconstriction , which may render cannulation more difficult . A gel formulation of amethocaine ( Ametop ™ ) is now commercially available . The aim of this study was to compare EMLA and Ametop ™ with regard to the degree of topical anesthesia afforded , the incidence of vasoconstriction and the ease of iv cannulation . Methods Thirty two ASA 1 adult volunteers had a # 16 gauge iv cannula inserted on two separate occasions using EMLA and Ametop ™ applied in a double blind fashion for topical anesthesia . Parameters that were recorded after each cannulation included visual analogue pain scores ( VAPS ) , the presence of vasoconstriction and the ease of cannulation , grade d as : 1 = easy , 2 = moderately difficult , 3 = difficult and 4 = failed . Results The mean VAPS ± SD after cannulation with Ametop ™ M was 12 ± 9.9 and with EMLA was 25.3 ± 16.6 ( P = 0.002 ) . Vasoconstriction occurred after EMLA application on 17 occasions and twice after Ametop ™ ( P = 0.001 ) . The grade of difficulty of cannulation was 1.44 ± 0.88 following EMLA and 1.06 ± 0.25 with Ametop ™ ( P = 0.023 ) . Conclusions Intravenous cannulation was less painful following application of Ametop ™ than EMLA . In addition , Ametop ™ caused less vasoconstriction and facilitated easier cannulation . Its use as a topical anesthetic agent is recommended , especially when iv access may be problematic . RésuméObjectifUn mélange eutectique d’anesthésiques locaux ( MEAL ) est souvent utilisé pour l’anesthésie topique lors d’une canulation intraveineuse ( iv ) . La vasoconstriction , qui est l’un des effets secondaires du MEAL , peut compliquer la mise en place d’une canule . Une présentation en gel d’améthocaïne ( Ametop ™ ) est maintenant offerte dans le commerce . Le but de la présente étude était de comparer le MEAL et l’Ametop ™ en regard du degré d’anesthésie topique fourni , de l’incidence de la vasoconstriction et de la facilité de la canulation iv . Méthode : On a inséré , en deux occasions séparées chez 32 volontaires adultes d’état physique ASA 1 , une canuleiv de calibre 16 en utilisant en double aveugle le MEAL et Ametop ™ pour réaliser l’anesthésie topique . Après chaque canulation , on a enregistré les paramètres suivants : les scores de douleur à l’échelle visuelle analogue ( EVA ) , la présence de vasoconstriction et la facilité de canulation notée 1 = facile , 2 = modérément difficile , 3 = difficile et 4 = impossible . RésultatsLes scores moyens à l’EVA ± l’écart type ont été de 12 ± 9,9 à la suite de la canulation avec Ametop ™ M et de 25,3 ± 16,6 après le MEAL ( P = 0,002 ) . La vasoconstriction est survenue en 17 occasions après l’application du MEAL et deux fois plus souvent après Ametop ™ ( P = 0,001 ) . Le degré de difficulté de canulation a été de 1,44 ± 0,88 après le MEAL et de 1,06 ± 0,25 après Ametop ™ ( P = 0,023 ) . Conclusion La canulation intraveineuse est moins douloureuse après l’application d’Ametop ™ que celle du MEAL . De plus , l’Ametop ™ a provoqué moins de vasoconstriction et a facilité l ’ introduction d’une canule . Son usage comme anesthésique topique est recomm and é , surtout lorsqu’une action rapide est nécessaire ou que l’accèsiv peut être problématique The purpose of this study was to assess patient 's perception of pain associated with peripheral intravenous ( i.v . ) cannulation , using 3 methods of applying local anesthetics . A prospect i ve , r and omized , quasi-experimental study was conducted , using a convenience sample of men and women , ASA physical status I , II , or III , undergoing outpatient or same-day surgery . Group 1 received a subcutaneous injection of 1 % lidocaine , group 2 received topical EMLA cream for 45 to 60 minutes , and group 3 received treatment with " Numby Stuff " for 40 mA minutes . After the intended analgesic treatment was complete , the patient was asked to rate the pain experienced during the skin-numbing process . An i.v . was then started using an 18-gauge i.v . catheter , and the patient again was asked to rate the amount of pain experienced with the catheter insertion . A visual analog scale was used as the tool of measurement for pain . Results of the study showed that group 1 experienced a higher treatment pain score than either group 2 or group 3 , while group 2 experienced a higher pain score when the i.v . was started than either group 1 or group 3 . Of the 3 methods tested , results seem to indicate that the Numby Stuff system using iontophoresis is the superior method for decreasing the pain associated with peripheral i.v . cannulation , and application of the analgesic method does not cause significant pain This study compared pain on application , pain on venipuncture , cost , and convenience of 4 analgesic agents used for venipuncture . A convenience sample of 280 preoperative subjects was assigned r and omly to 1 of 4 groups . Group 1 received 2.5 % lidocaine--2.5 % prilocaine cream ( LPC ) topically , Group 2 received dichlorotetrafluoroethane spray ( DCTF ) , Group 3 received 0.5 % lidocaine subcutaneously , and group 4 received normal saline with 0.9 % benzyl alcohol ( BA ) subcutaneously . A 7-point verbal descriptor scale measured pain on application , and a 100-mm visual analogue scale measured pain on venipuncture . Cost was measured and compared on unit-dose basis . Convenience was measured with a question naire survey completed by the investigators . There was no significant difference ( P < .05 ) among the groups for age , sex , ASA physical status , or difficulty of venipuncture . There was a significant difference in pain on application for all 4 agents ( P < .05 ) . The DCTF had the highest pain on application score ( 1.7 + /- 0.1 ) , while the LPC had no pain on application ( 0.0 + /- 0 ) . Lidocaine had a higher pain on application score ( 1.08 + /- 0.1 ) than the BA ( 0.52 + /- 0.1 ) but a lower score than DCTF . Lidocaine ( 1.3 + /- 0.3 ) was significantly less painful ( P < .05 ) on venipuncture than LPC ( 2.18 + /- 0.3 ) and DCTF ( 2.5 + /- 0.3 ) but was not significantly different than BA ( 1.92 + /- 0.3 ) . ( All scores are given as mean + /- SEM . ) There was a significant difference in cost and convenience among the 4 agents , with BA and lidocaine being the least expensive analgesic agents . Lidocaine , DCTF , and BA were equally convenient to use , while LPC was the least convenient , ( P < .05 ) . Lidocaine had low pain on venipuncture and low cost and convenience of use , but it was less than ideal in terms of pain on application . The BA had all the qualities of an ideal analgesic agent for venipuncture in this sample and should be considered as an analgesic agent for venipuncture A eutectic mixture of local anesthetics ( EMLA ) in cream form has been used as a topical anesthetic to reduce the pain of procedures penetrating the skin . It is generally applied for 45 to 60 minutes before the painful procedure . The purpose of this study was to determine whether a 20-minute application of EMLA is useful in reducing the pain of routine peripheral intravenous cannulation in the emergency department ( ED ) . A blinded , r and omized , placebo-controlled , paired trial compared the pain of intravenous cannulation in both h and s of study subjects : one h and was treated with 20-minute EMLA cream and the other h and was treated with 20-minute placebo cream . Forty subjects identified the more painful h and and scored pain measurements of each h and using a 10-cm visual analog scale . These data failed to demonstrate any significant benefit of EMLA compared with placebo . EMLA is not useful for intravenous cannulation when used for 20-minute application times . There may be more effective and less costly ways of reducing the pain of intravenous cannulation that patients would prefer STUDY OBJECTIVE We sought to determine the minimum clinical ly significant difference in visual analog scale ( VAS ) pain score for children . METHODS We performed a prospect i ve , single-group , repeated- measures study of children between 8 and 15 years presenting to an urban pediatric emergency department with acute pain . On presentation to the ED , patients marked the level of their pain on a 100-mm nonhatched VAS scale . At 20-minute intervals thereafter , they were asked to give a verbal categoric rating of their pain as " heaps better , " " a bit better , " " much the same , " " a bit worse , " or " heaps worse " and to mark the level of pain on a VAS scale of the same type as used previously . A maximum of 3 comparisons was recorded for each child . The minimum clinical ly significant difference in VAS pain score was defined as the mean difference between current and preceding scores when the subject reported " a bit worse " or " a bit better " pain . RESULTS Seventy-three children were enrolled in the study , yielding 103 evaluable comparisons in which pain was rated as " a bit better " or " a bit worse . " The minimum clinical ly significant difference in VAS score was 10 mm ( 95 % confidence interval 7 to 12 mm ) . CONCLUSION This study found the minimum clinical ly significant difference in VAS pain score for children aged 8 to 15 years ( on a 100-mm VAS scale ) to be 10 mm ( 95 % confidence interval 7 to 12 mm ) . In studies of population s , differences of less than this amount , even if statistically significant , are unlikely to be of clinical significance The minimal effective onset time of the new topical anaesthetic , formulation EMLA ( a eutectic mixture of lidocaine and prilocaine ) , was evaluated by the double‐blind technique in 53 female and 66 male patients ( median age 40 and 36 years , respectively ) subjected to intravenous cannulation . Conventional plotting and regression analysis failed to answer the question . The Cusum technique , originally design ed for industrial production control , could successfully be applied to solve the problem . It demonstrated a minimal effective EMLA application time of 45 min in adults BACKGROUND In a prospect i ve r and omized study , we compared topical 4 % amethocaine gel ( Ametop ) with 2 % lidocaine infiltration for analgesia for radial artery cannulation . A previous study had shown topical analgesia with EMLA cream reduced pain , shortened cannulation time , and improved success rates when compared with lidocaine infiltration . METHODS One hundred adult patients undergoing elective cardiac surgery were r and omized . Cannulation times and success rates were compared between the two groups . The quality of analgesia was assessed using a visual analogue scale ( VAS ) and four-point verbal pain scoring system . RESULTS Ninety-nine sets of data were analysed using Mann-Whitney U and chi-squared tests . Mean time to cannulation was 56 s in the amethocaine group ( interquartile range ( IQR ) 41 - 142 ) and 59 s in the lidocaine group ( IQR 40 - 105 ) . The median pain score on the VAS was 2 in both groups ( IQR 1 - 3.5 for amethocaine and 0 - 4 for lidocaine ) . CONCLUSIONS There was no significant difference between these two methods of analgesia for any measured variable We have prospect ively assessed pain and anxiety of spinal puncture in 180 adult patients r and omly allocated to one of three equal groups . On the morning of surgery group 1 had an EMLA patch , whereas group 2 and 3 had placebo patches . Group 2 also had infiltration analgesia with 2 ml lignocaine 2 % with adrenaline , immediately before the block . Spinal anaesthesia was performed with 25 gauge sharp needles without introducer or 25,27 gauge blunt needles with 20,22 gauge introducers . Patients assessed the spinal puncture pain on a 10‐cm visual analogue scale immediately after removal of the needle . Pain scores were significantly lower in group 1 ( EMLA ) , median 0.75 , than in group 2 ( placebo , infiltration analgesia ) , median 1.75 , and group 3 ( placebo ) , median 1.80 , p < 0.0001 . Pain intensity was less than expected in more patients in the EMLA group than in the other two groups , p = 0.034 . However , the decision to accept/reject spinal anaesthesia in the future was not influenced by the pain of lumbar puncture . We conclude that application of an EMLA patch is a simple and effective method to provide adequate analgesia for spinal puncture , which also helps to allay patients ' fears of spinal anaesthesia OBJECTIVE A double-r and omized , blinded crossover trial was performed to assess the efficacy of ELA-Max ( 4 % liposomal lidocaine ) as compared with eutectic mixture of local anesthetics ( EMLA ) for pain relief during pediatric venipuncture procedures . Safety was assessed by evaluation for topical or systemic effects and measurement of serum lidocaine concentrations . METHODS A total of 120 children who were scheduled for repeat venipuncture for non- study -related reasons at 2 sites participated in the study . Patients were doubly r and omized to treatment regimen ( study medication application time of either 30 or 60 minutes ) and to the order of application of the topical anesthetics for each venipuncture . The primary outcome measures were the child 's rating of pain immediately after the venipuncture procedures using a 100-mm visual analog scale ( VAS ) tool and the parent 's and blinded research observer 's Observed Behavioral Distress scores . RESULTS Both ELA-Max and EMLA seemed to alleviate venipuncture pain . There was no clinical ly or statistically significant difference in the patient VAS scores within the 30-minute or 60-minute treatment groups , and there was no clinical or statistical difference in VAS scores between the 30-minute ELA-Max treatment without occlusion and the 60-minute EMLA treatment with occlusion . There were no clinical ly or statistically significant differences between treatment with ELA-Max and EMLA in parental or blinded research er Observed Behavioral Distress scores , the most frequent response at any observation time being " no distress . " CONCLUSION This study demonstrates that a 30-minute application of ELA-Max without occlusion is as safe and as effective for ameliorating pain associated with venipuncture as a 60-minute application of the prescription product EMLA requiring occlusion Eutectic mixture of local anaesthetics ( EMLA ) cream with Tegaderm was compared with prepackaged EMLA patch with regard to analgesic effect , adhesiveness and local reactions during venepuncture in 178 children from three to ten years . One EMLA patch , or half the contents of a 5 g tube of EMLA cream plus Tegaderm was applied to the dorsum of one h and or antecubital fossa for a minimum of 60 min before venepuncture . The subject and observer assessed the degree of pain on a threepoint verbal rating scale . The adhesion of the patch vs Tegaderm to the skin and local reactions were recorded . There was no difference between the two groups in pain associated with venepuncture ; 95 % of the EMLA patch group and 94 % of the EMLA cream group reported no or slight pain . There was no difference between the two treatment groups in terms of overall local reactions . The patch was less adhesive ( P < 0.001 ) , but this had no apparent influence on its effectiveness . In conclusion , EMLA patch is equivalent to 5 % EMLA cream ( 2.5 g ) in cutaneous pain relief when used for venepuncture in children . RésuméCette étude compare l’efficacité , l’adhésivité et les réactions locales du mélange eutectique de crème d’anesthésiques locaux ( EMLA ) appliqué sous une pellicule de Tegaderm avec un timbre préenduit d’EMLA au regard de l’effet analgésique , l’adhésivité , et des réactions locales lors d’une ponction veineuse réalisée chez 178 enfants âgés de trois à dix ans . Un timbre ou la moitié d’un tube de 5 g de crème EMLA avec Tegaderm est appliqué au dos de la main ou au pli du coude pendant au moins 60 min avant la ponction . Le sujet et l’observateur évaluent la douleur sur une échelle verbale à trois degrés . L’adhérence cutanée du timbre et celle du Tegaderm et les réactions locales sont enregistrées . On ne trouve pas de différence entre les deux groupes au regard de la douleur : 95 % du groupe EMLA-timbre et 94 % du groupe EMLA-crème ne rapportent que peu ou pas de douleur . Il n’y a pas de différence entre les groupes au regard des réactions locales . Le timbre adhère moins bien ( P < 0,001 ) , mais ceci n’a aucune influence apparente sur l’efficacité . En conclusion , le timbre EMLA équivaut à la crème ( 2,5 g ) pour le soulagement de la douleur cutanée lorqu’on les utilise pour la ponction veineuse chez l’enfant INTRODUCTION Arterial puncture is a painful procedure requiring prior local anesthesia . Various products are available for pain relief , among them EMLA anesthetic cream . OBJECTIVE To compare pain from simple puncture of the radial artery performed with or without application of EMLA anesthetic cream and after infiltration of mepivacaine . PATIENTS AND METHODS A prospect i ve , r and om double-blind study of 153 patients in three groups : group A , 51 patients who were applied 1 g of EMLA cream ; group B , 52 patients who were applied 1 g of placebo cream ; and group C , 50 patients who received infiltration of 0.2 ml of 1 % mepivacaine . Pain was assessed on a 10 cm visual analog scale ( 0 , absence of pain ; 10 , greatest imaginable pain ) . RESULTS Pain intensity reported by the patients was 2.6 + /- 1.8 in group A , 2.9 + /- 1.8 in group B and 1.6 + /- 1.8 in group C. The results for group C were statistically different from those for groups A and B. The difference between groups A ( EMLA ) and B ( placebo ) , however , was not statistically significant . CONCLUSIONS Mepivacaine infiltration is the more effective method for minimizing pain from puncture of the radial artery . EMLA anesthetic cream is not effective against pain caused by this procedure STUDY OBJECTIVE To compare patient and practitioner assessment s of pain associated with commonly performed emergency department procedures and use of anesthetics before these procedures . METHODS This was a prospect i ve , observational , cross-sectional study conducted at a university-based ED with a convenience sample of ED patients . Research assistants recorded the procedure performed and historical and demographic information on st and ardized data collection instruments . After each procedure , both the patient and practitioner independently recorded assessment s of patient pain on a 100-mm visual analog scale ( VAS ) . Use of preprocedure anesthetics and patient preferences regarding their use were also identified . Categorical variables were analyzed by chi(2 ) tests . Patient and practitioner VAS scores were compared using a paired t test ; alpha was preset at .05 . Correlation coefficients were calculated to assess correlation between patient and practitioner pain scores . RESULTS A total of 1,171 procedures were evaluated for the 15 most common procedures performed . The mean patient age was 42.8+/-18.7 years and 46.1 % were male . Overall , the mean patient VAS was 20.8 mm+/-25.1 mm ; the mean practitioner VAS was 23.5 mm+/-20.3 mm . The mean difference between groups was 3.0 mm ( 95 % confidence interval [ CI ] , 1.3 to 4.1 ) . Correlation between patient and practitioner pain scores for individual procedures was poor to fair ( r=.26 to.68 ) . The most painful procedures according to patients in descending order were nasogastric intubation , abscess drainage , fracture reduction , and urethral catheterization . Local anesthetics were administered in 12.8 % of procedures yet would be requested before similar future procedures by 17.1 % of patients . Patients who would choose local anesthetics in the future gave higher pain scores than those who would not ( 43.3 mm versus 16.3 mm ; mean difference=27.0 mm , 95 % CI , 22.2 to 31.8 mm ) . CONCLUSION The most painful procedures for ED patients were nasogastric intubation , incision and drainage of abscesses , fracture reduction , and urethral catheterization . Although practitioners also identified these procedures as most painful , the correlation between patient and practitioner pain assessment s in individual patients was highly variable . Overall use of anesthetics before these procedures was low . Practitioners should be attentive to their patients ' individual anesthetic needs before performing painful procedures The emulsion of lidocaine and prilocaine ( EMLA ) is effective in preventing the pain of venipuncture in children . It is therefore important to identify children who could benefit the most from EMLA . We studied the safety and feasibility of two methods of application of EMLA ( patch and cream ) in a r and omized , open-label trial of EMLA patch versus EMLA cream in 160 children with chronic diseases undergoing venipuncture . EMLA patch or cream was applied 60 to 120 min before puncture . Pain was assessed by the children using a visual analogue score . Children also scored the pain of their last puncture and the pain of removing the tape . EMLA patch and cream had similar efficacy ( visual analogue scores for the venipuncture were 8.5 ± 16 and 9.5 ± 17 out of 100 , respectively ) . Side effects occurred in similar frequencies in the two groups . Adhesiveness of the patch was less effective than that of the cream with Tegaderm . Age was a major determinant of pain perception ; younger children recalled more severe pain in their previous puncture . Children recently diagnosed had higher visual analogue scores than those with a long history of chronic disease . We concluded that EMLA patch and cream have a similar efficacy in children undergoing venipuncture . Young children recently diagnosed with chronic disease are most likely to benefit from EMLA At the end of a long week in the office , you sink back into your chair , reflecting on some of the more memorable patients you cared for and counseled . Through gentle history taking , you discovered that urinary incontinence is the underlying cause of an elderly patient 's increasing social isolation . During a careful physical examination , you detected bruising on the torso of a woman with chronic headaches and began to explore the longst and ing abusive relationship between the woman and her alcoholic partner . You discontinued procainamide therapy in a 72-year-old man who had asymptomatic premature ventricular contractions after myocardial infa rct ion . To prevent bleeding from esophageal varices , you started -blocker therapy in a woman with long-st and ing cryptogenic cirrhosis and portal hypertension . In couples ' therapy , discussing the future quality of life of a middle-aged gay man with human immunodeficiency virus infection , you journeyed through emotionally intense dialogue about advance directives . You presented the risk factors for major and minor bleeding to a 39-year-old woman who was considering warfarin therapy because of recently diagnosed atrial fibrillation and valvular heart disease . You listened to , made diagnoses for , treated , advised , and comforted many patients . Yet there were some hiccoughs in your practice along the way . You stumbled while debating the pros and cons of breast cancer screening with a healthy 48-year-old woman who has been staying current with information on the Internet . You question ed the merits of a personalized walking program suggested to you by a motivated 66-year-old man with severe claudication . Explaining that you wanted to review the best current evidence on these issues , you resolved to address your uncertainties before these patients made their next office visits , in a week 's time . Sighing deeply , you acknowledge that you have little time to read . You subscribe to three journals , which you browse months after they arrive-either when your journal stack becomes precariously high or when your guilt is sufficiently motivational . You sometimes find the conclusions of individual articles conflicting or confusing . You know that some of the decisions and suggestions you made this week , specifically your decisions about stopping procainamide therapy and starting -blocker therapy and your advice about bleeding risks from anticoagulant therapy , were based on the best current research evidence [ 1 - 3 ] . On the other h and , your patients ' inquiries about breast cancer screening and exercise treatment for claudication highlight your need for a concise , current , rigorous synthesis of the best available evidence on each of these topics : in brief , a systematic review [ 4 , 5 ] . Incorporating Research Evidence into Clinical Decision Making The foregoing scenario is familiar to practitioners . In a typical week , we encounter patients with diverse problems ; exercise numerous clinical , interpersonal , and technical skills ; and make many decisions . The factors that affect these decisions and their outcomes are complex . For instance , each patient has unique sociodemographic characteristics , cultural circumstances , and personal preferences . Each physician has unique knowledge , experiences , and values . Moreover , practitioners and their patients make decisions within the context of a rapidly changing health care system that influences the availability , accessibility , and cost of diagnostic tests and therapies [ 6 ] . Timely , useful evidence from the biomedical literature should be an integral component of clinical decision making . If one treatment has been shown to be better than another , we need to know , so that we can recommend the treatment to the appropriate patients . The worldwide effort to develop new tests and treatments , and to determine their usefulness , has never been stronger , and our patients and their families expect us to be fonts of the knowledge that results from this effort [ 7 ] . Unfortunately , it is easy for current best research evidence to pass us by [ 8 ] . We may lack the time , motivation , and basic skills needed to find , critically appraise , and synthesize information , all of which we must do if we are to integrate the results of original studies into our practice . Fortunately , several potent methods are emerging that can greatly enhance our ability to interpret and apply research evidence ; foremost among them is the systematic review . This article begins a series in Annals that will examine systematic review s in detail and explore their many applications . Systematic review s represent the best chance that most practitioners will have to underst and and accurately apply the key signals arising from the robust and increasingly productive search for solutions to medical problems . A properly conducted systematic review faithfully summarizes the evidence from all relevant studies on the topic of interest , and it does so concisely and transparently . What Is a Systematic Review ? Systematic review s are scientific investigations in themselves , with pre-planned methods and an assembly of original studies as their subjects . They synthesize the results of multiple primary investigations by using strategies that limit bias and r and om error [ 9 , 10 ] . These strategies include a comprehensive search of all potentially relevant articles and the use of explicit , reproducible criteria in the selection of articles for review . Primary research design s and study characteristics are appraised , data are synthesized , and results are interpreted . When the results of primary studies are summarized but not statistically combined , the review may be called a qualitative systematic review . A quantitative systematic review , or meta- analysis , is a systematic review that uses statistical methods to combine the results of two or more studies . The term overview is sometimes used to denote a systematic review , whether quantitative or qualitative . Summaries of research that lack explicit descriptions of systematic methods are often called narrative review s. Review articles are one type of integrative publication ; practice guidelines , economic evaluations , and clinical decision analyses are others . These other types of integrative articles often incorporate the results of systematic review s. For example , practice guidelines are systematic ally developed statements intended to assist practitioners and patients with decisions about appropriate health care for specific clinical circumstances [ 11 ] . Evidence -based practice guidelines are based on systematic review s of the literature , appropriately adapted to local circumstances and values . Economic evaluations compare both the costs and the consequences of different courses of action ; the knowledge of consequences that are considered in these evaluations is often generated by systematic review s of primary studies . Decision analyses quantify both the likelihood and the valuation of the expected outcomes associated with competing alternatives . Differences between Systematic and Narrative Review s All review s , narrative and systematic alike , are retrospective , observational research studies and are therefore subject to systematic and r and om error . Accordingly , the quality of a review - and thus its worth-depends on the extent to which scientific review methods have been used to minimize error and bias . This is the key feature that distinguishes traditional narrative review s from systematic review s ( Table 1 ) . If a review is prepared according to the steps outlined in the right column of Table 1 , it is more likely to be systematic and to provide unbiased conclusions . If review methods approximate those found in the middle column of Table 1 , the article is more likely to be a narrative review , and the conclusions are less likely to be based on an unbiased summary of all relevant evidence . Table 1 . Differences between Narrative Review s and Systematic Review s Systematic review s are generated to answer specific , often narrow , clinical questions in depth . These questions can be formulated explicitly according to four variables : a specific population and setting ( such as elderly out patients ) , the condition of interest ( for example , hypertension ) , an exposure to a test or treatment ( such as pharmacologic management ) , and one or more specific outcomes ( such as cardiovascular and cerebrovascular events and mortality ) [ 12 ] . Thus , an example of a well-formulated , clinical ly relevant question is , Does pharmacologic treatment of hypertension in the elderly prevent strokes and myocardial infa rct ions or delay death ? If the question that is driving the review is not clear from the title , abstract , or introduction , or if no methods section is included , the paper is more likely to be a narrative review than a systematic review [ 13 ] . Most narrative review articles deal with a broad range of issues related to a given topic rather than addressing a particular issue in depth [ 9 ] . For example , a narrative review on diabetes ( such as that which might be found in a textbook chapter ) might include sections on the physiology and pathophysiology of carbohydrate , lipid , and protein metabolism ; the epidemiology of and prognosis associated with diabetes ; diagnostic and screening approaches ; and preventive , therapeutic , rehabilitative , and palliative interventions . Thus , narrative review s may be most useful for obtaining a broad perspective on a topic ; they are less often useful in furnishing quantitative answers to specific clinical questions . Narrative review s are appropriate for describing the history or development of a problem and its management . Narrative review s may better describe cutting-edge developments if research is scant or preliminary or if studies are very limited by flawed design or execution [ 13 ] . They may be particularly useful for discussing data in light of underlying theory and context . Narrative review s can draw analogies and can conceptually integrate two independent fields of research , such as The use of a local anaesthetic cream ( EMLA ; Astra ) for arteriovenous fistula cannulation was compared to placebo in a double-blind r and omised manner in 26 patients undergoing chronic haemodialysis who were currently using injections of lignocaine . The EMLA cream was highly effective compared to placebo ( P less than 0.001 ) on visual analogue and verbal rating scales as well as ease of venepuncture ( P less than 0.01 ) . It also gave more pain relief and improved the ease of venepuncture compared to lignocaine injections . Patients expressed a strong preference for the EMLA cream , which has advantages that outweigh the cost and convenience factors Using a r and omized , controlled study , the investigators evaluated and compared the effects of local anesthesia versus no anesthesia on pain associated with peripherally inserted central catheter ( PICC ) insertion . A sample of 42 subjects was selected and divided into three groups . Group 1 received EMLA cream . Group 2 received buffered lidocaine . Group 3 ( the control group ) did not receive a local anesthetic . The short form of the McGill Pain Question naire was used to measure pain quality and intensity . A numerical Visual Analogue Scale accompanied the question naire and measured overall pain intensity . Results showed that buffered lidocaine was statistically superior to EMLA cream or no anesthetic in relieving pain associated with PICC insertion We have evaluated the efficacy and safety of a preparation of 4 % amethocaine gel in alleviating the pain of venous cannulation in children . In an initial open study of 148 children , clinical ly acceptable anaesthesia was achieved in 92 % of cases . The preparation was then compared with 5 % EMLA cream in a single-blind study in 94 patients using an application time of 40 min . We found clinical ly acceptable conditions in 85 % of patients receiving amethocaine gel compared with 66 % in the EMLA group . There were no significant adverse effects noted in each group , although 37 % of those children treated with amethocaine gel showed localized erythema at the application site . The results suggest that amethocaine gel has greater efficacy and a faster onset time than EMLA cream when used for this purpose in children STUDY OBJECTIVE To determine the amount of change in pain severity , as measured by a visual analog scale , that constitutes a minimum clinical ly significant difference . METHODS Patients 18 years of age or older who presented with acute pain result ing from trauma were enrolled in this prospect i ve , descriptive study . The setting was an urban county hospital emergency department with a Level 1 trauma center . In the course of a brief interview , patients were asked to indicate their current pain severity with a single mark through a st and ard 100-mm visual analog scale . At intervals of 20 minutes for the next 2 hours , patients were asked to repeat this measurement and , in addition , to contrast their present pain severity with that at the time of the previous measurement . They were to indicate whether they had " much less , " " a little less , " " about the same , " " a little more , " or " much more " pain . All contrasts were made without reference to prior visual analog scale measurements . A maximum of six measurements of pain change were recorded per patient . Measurements ended when the patient left the ED or when the patient reported a pain score of zero . The minimum clinical ly significant change in visual analog scale pain score was defined as the mean difference between current and preceding visual analog scale scores when the subject noted a little less or a little more pain . RESULTS Forty-eight subjects were enrolled , and 248 pain contrasts were recorded . Of these contrasts , 41 were rated as a little less and 39 as a little more pain . The mean difference between current and preceding visual analog scale scores in these 80 contrasts was 13 mm ( 95 % confidence interval , 10 to 17 mm ) . CONCLUSION The minimum clinical ly significant change in patient pain severity measured with a 100-mm visual analog scale was 13 mm . Studies of pain experience that report less than a 13-mm change in pain severity , although statistically significant , may have no clinical importance |
13,852 | 27,551,826 | Most interventions improved providers ' interpersonal , patient-centered interviewing skills .
Interventions that targeted parents involved booklets and role-playing to encourage questions .
They improved parents ' satisfaction and communication .
An intervention that targeted youth used a video portraying how children can communicate better with physicians .
Once the children aged 5 - 15 years watched the video , they wrote questions for their physicians prior to the medical visit .
The experimental group of children had better rapport with physicians and could recall recommendations about medications more often than the control group . | RATIONALE Research related to effective communication between children/parents and medical providers is limited .
OBJECTIVE To review interventions seeking to improve communication between children/parents and medical providers . | BACKGROUND Involvement of family in bedside rounds is one strategy to implement family-centered care to help families get clear information about their child , and be actively involved in decision-making about care . However in developing countries such as Pakistan , daily bedside rounds include the physician , residents , medical students and a nurse/technician . Parents are not currently a part of these rounds . OBJECTIVE To assess whether family-centered rounds improve parents ' and health care professionals ' satisfaction , decrease patient length of stay , and improve time utilization when compared to traditional practice rounds in a population with a low literacy rate , socioeconomic status , and different cultural values and beliefs . DESIGN A non-r and omized before-after study design . SETTING A private hospital in Karachi , Pakistan . PARTICIPANTS A convenience sample of 82 parents , whose children were hospitalized for a minimum of 48h , and 25 health care professionals able to attend two consecutive rounds . METHODS During the before phase , traditional bedside rounds were practice d ; and during after phase , family-centered rounds were practice d. Parents and health care professionals completed a question naire on the second day of rounds . An observational form facilitated data collection on length of stay and time utilization during . RESULTS Parents ' ratings during the family-centered rounds were significantly higher for some parental satisfaction items : evidence of team work ( p=0.007 ) , use of simple language during the rounds ( p=0.002 ) , feeling of inclusion in discussion at rounds ( p=0.03 ) , decision making ( p=0.01 ) , and preference for family-centered rounds ( p=<0.001 ) . No significant differences were found in health care professionals ' satisfaction between rounds . Patient length of stay was significantly reduced in the family-centered rounds group , while no significant difference was found in the duration of rounds . Family-centered rounds served as an opportunity for parents to correct/add to patient history or documentation . CONCLUSION Parents were satisfied with both forms of rounds ; however , they appeared to have a greater preference for family-centered rounds than health care professionals . Family-centered rounds were a re source for Pakistani parents , enabling direct communication with the medical team without impacting on the time required to complete rounds . Family-centered rounds may improve quality of care such as decreasing length of stay or preventing critical incidents OBJECTIVE It was hypothesized that parents exposed to a communication skills intervention would participate ( e.g. , ask questions , express concerns ) in a pre-surgical consultation more than parents in the control group . METHODS Sixty-five parents of prospect i ve pediatric surgery patients were r and omly assigned to either a communication skills intervention ( booklet mailed prior to the consultation ) or control group . Only initial consultation parents were included , no follow-ups . Audio-recordings of the medical consultations were obtained and the transcripts analyzed utilizing a content-coding system to determine patient participation . Also , parents were given a health literacy test ( s-TOFHLA ) and a post-interview question naire to gather demographic data . RESULTS Intervention parents participated overall significantly more than control parents . Follow-up analyses revealed that intervention parents asked significantly more questions , and engaged in significantly more information verifying and expressing of concerns . There were no significant differences for parents ' assertive statements or information provision . Other significant predictors of parents ' participation were consultation length and parents ' income . CONCLUSION The intervention tested in this study promoted parents ' participation in a pre-surgical consultation . As such , it has the potential to improve information exchange between parents and physicians with positive implication s for informed consent . PRACTICE IMPLICATION S Providing parents with communication guidelines prior to a surgical consultation may improve physician-patient communication OBJECTIVE Problems with clinician-patient communication negatively impact newborn screening , genetics , and all of healthcare . Training programs teach communication , but educational methods are not feasible for entire population s of clinicians . To address this healthcare quality gap , we developed a Communication Quality Assurance intervention . METHODS Child health providers volunteered for a r and omized controlled trial of assessment and a report card . Participants provided telephone counseling to a st and ardized parent regarding a newborn screening result showing heterozygous status for cystic fibrosis or sickle cell disease . Our rapid-throughput timeline allows individualized feedback within a week . Two encounters were recorded ( baseline and after a r and om sample received the report card ) and abstract ed for four groups of communication quality indicators . RESULTS 92 participants finished both counseling encounters within our rapid-throughput time limits . Participants r and omized to receive the report card improved communication behaviors more than controls , including request for teach-back ( p<0.01 ) , opening behaviors ( p=0.01 ) , anticipate/vali date emotion ( p<0.001 ) and the ratio of explained to unexplained jargon words ( p<0.03 ) . CONCLUSION The rapid-throughput report card is effective at improving specific communication behaviors . PRACTICE IMPLICATION S Communication can be taught , but this project shows how healthcare organizations can assure communication quality everywhere . Further implementation could improve newborn screening , genetics , and healthcare in general OBJECTIVE . We evaluated the effectiveness of a continuing medical education program , Physician Asthma Care Education , in improving pediatricians ’ asthma therapeutic and communication skills and patients ’ health care utilization for asthma . METHODS . We conducted a r and omized trial in 10 regions in the United States . Primary care providers were recruited and r and omly assigned by site to receive the program provided by local faculty . The program included 2 interactive seminar sessions ( 2.5 hours each ) that review ed national asthma guidelines , communication skills , and key educational messages . Format included short lectures , case discussion s , and a video modeling communication techniques . We collected information on parent perceptions of physicians ’ communication , the child ’s asthma symptoms , and patients ’ asthma health care utilization . We used multivariate regression models to determine differences between control and intervention groups . RESULTS . A total of 101 primary care providers and a r and om sample of 870 of their asthma patients participated . After 1 year , we completed follow-up telephone interviews with the parents of 731 of the 870 patients . Compared to control subjects , parents reported that physicians in the intervention group were more likely to inquire about patients ’ concerns about asthma , encourage patients to be physically active , and set goals for successful treatment . Patients of physicians that attended the program had a greater decrease in days limited by asthma symptoms ( 8.5 vs 15.6 days ) , as well as decreased emergency department asthma visits ( 0.30 vs 0.55 visits per year ) . CONCLUSIONS . The Physician Asthma Care Education program was used in a range of locations and was effective in improving parent-reported provider communication skills , the number of days affected by asthma symptoms , and asthma health care use . Patients with more frequent asthma symptoms and higher health care utilization at baseline were more likely to benefit from their physician ’s participation in the program OBJECTIVE To determine whether augmenting st and ard feedback on resident performance with a multi source feedback intervention improved pediatric resident communication skills and professionalism . DESIGN R and omized controlled trial . SETTING Children 's Hospital Medical Center , Cincinnati , Ohio , from June 21 , 2004 , to July 7 , 2005 . PARTICIPANTS Thirty-six first-year pediatric residents . INTERVENTIONS Residents assigned to the multi source feedback group ( n = 18 ) completed a self- assessment , received a feedback report about baseline parent and nurse evaluations , and participated in a tailored coaching session in addition to receiving st and ard feedback . Residents in the control group ( n = 18 ) received st and ard feedback only . The control group and their residency directors were blinded to parent and nurse evaluations until the end of the study . MAIN OUTCOME MEASURES Residents ' specific communication skills and professional behaviors were rated by parents and nurses of pediatric patients . Both groups were evaluated at baseline and after 5 months . Scores were calculated on each item as percentage in the highest response category . RESULTS Both groups had comparable baseline characteristics and ratings . Parent ratings increased for both groups . While parent ratings increased more for the multi source feedback group , differences between groups were not statistically significant . In contrast , nurse ratings increased for the multi source feedback group and decreased for the control group . The difference in change between groups was statistically significant for communicating effectively with the patient and family ( 35 % ; 95 % confidence interval , 11.0%-58.0 % ) , timeliness of completing tasks ( 30 % ; 95 % confidence interval , 7.9%-53.0 % ) , and demonstrating responsibility and accountability ( 26 % ; 95 % confidence interval , 2.9%-49.0 % ) . CONCLUSION A multi source feedback intervention positively affected communication skills and professional behavior among pediatric residents Background To assess the student perspective on acceptability , realism , and perceived effect of communication training with peer role play ( RP ) and st and ardised patients ( SP ) . Methods 69 prefinal year students from a large German medical faculty were r and omly assigned to one of two groups receiving communication training with RP ( N = 34 ) or SP ( N = 35 ) in the course of their paediatric rotation . In both groups , training addressed major medical and communication problems encountered in the exploration and counselling of parents of sick children . Acceptability and realism of the training as well as perceived effects and applicability for future parent-physician encounters were assessed using six-point Likert scales . Results Both forms of training were highly accepted ( RP 5.32 ± .41 , SP 5.51 ± .44 , n.s . ; 6 = very good , 1 = very poor ) and perceived to be highly realistic ( RP 5.60 ± .38 , SP 5.53 ± .36 , n.s . ; 6 = highly realistic , 1 = unrealistic ) . Regarding perceived effects , participation was seen to be significantly more worthwhile in the SP group ( RP 5.17 ± .37 , SP 5.50 ± .43 ; p < .003 ; 6 = totally agree , 1 = do n't agree at all ) . Both training methods were perceived as useful for training communication skills ( RP 5.01 ± .68 , SP 5.34 ± .47 ; 6 = totally agree ; 1 = do n't agree at all ) and were considered to be moderately applicable for future parent-physician encounters ( RP 4.29 ± 1.08 , SP 5.00 ± .89 ; 6 = well prepared , 1 = unprepared ) , with usefulness and applicability both being rated higher in the SP group ( p < .032 and p < .009 ) . Conclusions RP and SP represent comparably valuable tools for the training of specific communication skills from the student perspective . Both provide highly realistic training scenarios and warrant inclusion in medical curricula . Given the expense of SP , deciding which method to employ should be carefully weighed up . From the perspective of the students in our study , SP were seen as a more useful and more applicable tool than RP . We discuss the potential of RP to foster a greater empathic appreciation of the patient perspective To determine whether st and ardized instructions enhance communication of discharge information , we provided 197 parents of children in whom otitis media was diagnosed with one of three types of instruction at the time of discharge from a pediatric emergency department : ( 1 ) instruction by individual housestaff and medical students after consultation with an attending physician ( control group ) ; ( 2 ) st and ardized verbal instructions given by housestaff and students trained in their use ( verbal group ) ; or ( 3 ) the same instructions given to the verbal group , together with a type-written copy of the information to take home ( verbal + written group ) . Prior to leaving the emergency department and , again , by phone , 1 and 3 days later , parents were question ed concerning the prescribed medication 's name , dose , frequency , and duration of administration ( medication data ) , three signs of improvement , and eight signs indicating the need for medical advice ( worrisome signs ) . The mean percentage of correct responses per parent in each group was computed for each information category . Both at exit interview and at follow-up , parents receiving either form of st and ardized instructions showed significantly greater knowledge of information related to their child 's illness than did controls . Information regarding medication data was more likely to be communicated to parents in all groups than were signs of improvement or worrisome signs . The addition of written instructions to st and ardized verbal instructions did not improve parental recall of discharge information The Physician Asthma Care Education ( PACE ) program significantly improved asthma prescribing and communication behaviours of primary care paediatricians in the USA . We tested the feasibility and acceptability of a modified PACE program with Australian general practitioners ( GP ) and measured its impact on self-reported consulting behaviours in a pilot study . Recruitment took place through a local GP division . Twenty-five GP completed two PACE Australia workshops , which incorporated paediatric asthma management consistent with Australian asthma guidelines and focussed on effective communication strategies . Program feasibility , usefulness and perceived benefit were measured by question naires before the workshop and 1 month later , and an evaluation question naire after each workshop . GP were universally enthusiastic and supportive of the workshops . The most useful elements they reported were communication skills , case studies , device demonstrations and the toolkit provided . GP self reports of the perceived helpfulness of the key communication strategies and their confidence in their application and reported frequency of use increased significantly after the workshops . The PACE program shows promise in improving the way in which Australian GP manage asthma consultations , particularly with regard to doctor-patient communication . The impact ofthe modified PACE Australia program on the processes and outcomes ofGP care ofchildren with asthma is now being measured in a r and omised controlled trial INTRODUCTION Following the recent amendment to the Medical Education Act in Germany ( Approbationsordnung 2002 ) and the abolition of the preliminary approbation for early residency ( AiP ) , the discussion increasingly focuses on the restructuring of German post-graduate medical training . The training should include well-defined learning objectives and an educational concept with a central emphasis on communication skills training . In the German-speaking countries there has as yet been no publication of a structured training course for the improvement of communication skills in the context of post-graduate education . METHODS Jointly design ed by the University of Heidelberg 's Clinic of Internal Medicine and Clinic of Paediatrics , this study aim ed to measure the effect of a training programme for h and ling problems and difficult situations arising in the communication with parents and patients . 28 paediatric residents took part in a r and omised controlled trial using st and ardized patients and video-feedback ( intervention group : N = 14 ; control group : N = 14 ) . Upon completion of the study , the control group also received training and was subsequently evaluated . The training course consisted of four units , lasting 90 minutes each . Both the acceptance of the training units and the self-evaluation of communication skills in dealing with parents were subject to assessment . RESULTS The participating residents acknowledged the training course to be an extremely useful tool for improving their communication skills and confidence in dealing with the parents of ill children . A pre-post comparison of self-assessed communication skills revealed a significant increase in the intervention group , but not in the control group . DISCUSSION The structured training course presented in the current study proved highly effective and should serve as a model for a compulsory component of a post-graduate training Abstract Paediatric care places great dem and s on interpersonal communication skills , especially as regards the h and ling of psychosocial issues . Recent shifts in paediatric morbidity and increases in patient empowerment furthermore emphasize the need for continuing paediatric education in communication skills . It is , however , debatable , whether after residency paediatric education can influence paediatrician performance . This study evaluated the effects of a 5-day experiential communication training by means of a pretest/post-test control group design . A total of 21 consulting paediatricians ( 10 experimental , 11 control group paediatricians ) videotaped two series of consecutive outpatient encounters . Compared with the untrained control group , trained paediatricians asked more psychosocial questions and looked at the patients and their parents more often . In addition , they gave patients and parents more room to talk . No difference was found in the length of the outpatient visits . Conclusion Paediatric education after residency influences paediatricians ' verbal and nonverbal communication skills positively , especially as regards h and ling psychosocial issues . On the basis of these findings , it appears worthwhile to encourage continuing paediatric education in interpersonal communication skills OBJECTIVE To investigate the effect of communication skills training on doctors ' and nurses ' self-efficacy , to explore how training courses influence the initial experience of self-efficacy and to identify determinants of health professionals ' self-efficacy . METHODS The study was conducted as a r and omized trial . Clinicians in the intervention group received a 5 day communication course and the control group received no intervention . The impact of the intervention was evaluated by means of question naires measuring the effect of communication courses on changes in doctors ' and nurses ' self-efficacy . RESULTS Clinicians who participated in the communication course improved their self-efficacy for specific communication tasks with up to 37 % . The improvements remained constant for the following 6 months . The training course did not influence the initial experience of self-efficacy . CONCLUSION Communication skills training can improve clinicians ' evaluation of his or her ability to perform a specific communication task - measured as self-efficacy . PRACTICE IMPLICATION S Communication courses can be used to improve doctors ' and nurses ' ability to perform some of the essential communicative dem and s they are facing in daily praxis A brief educational intervention to promote effective communication between physicians , children , and parents during pediatric office visits was design ed and tested . A r and omized clinical trial involving 141 children ( 5- to 15-year-olds ) tested the effectiveness of the intervention to improve the process and outcome of medical care . The intervention was contained in three brief videotapes ( one each for parents , physicians , and patients ) and in accompanying written material s. Material s were design ed to build skills and motivation for increased child competence and participation during pediatric medical visits . Control subjects saw health education videotapes and received material s comparable in length with those of experimental subjects . Postintervention medical visit process was analyzed using videotapes of visits . Visit outcomes , assessed with st and ardized instruments and interviews , included children 's rapport with physicians , children 's anxiety , children 's preference for an active health role , children 's recall of information , parents ' satisfaction with the medical visit , and physician satisfaction . Results indicated that physicians in the intervention group , compared with their counterparts in the control group , more often included children in discussion s of medical recommendations ( 50 % vs 29 % , t = 2.39 , P less than .05 ) ; that children in the intervention group , compared with control children , recalled more medication recommendations ( 77 % vs 47 % , P less than .01 ) and reported greater satisfaction and preference for an active health role ; and that the intervention and control groups did not differ in parent satisfaction , physician satisfaction , or child anxiety . The results suggest that a brief educational intervention administered during waiting room time can positively impact physician-child rapport and children 's preference for an active role in health and their acquisition of medical information OBJECTIVE Training in communication can change clinician behaviors , but brief training may function by altering attitudes rather than teaching new skills . We used data from a trial of mental health training for office-based primary care to determine indicators of uptake that predicted parent and child outcomes . METHODS Clinicians ( n=50 ) were r and omized to be controls or receive training . Uptake was determined comparing pre- and post-training visits with st and ardized patients ( SPs ) coded for skills and patient centeredness . Clinical outcomes were assessed by recruiting and following 403 children/youth ages 5 - 16 making visits to participants . At 6 months , change in mental health was assessed by parent and youth reports using the Strengths and Difficulties Question naire . RESULTS Trained clinicians used more agenda setting , time , and anger management skills than controls and showed increased patient centeredness toward SP parents , but not adolescents . Increased patient-centeredness toward parents predicted improvement in child/youth symptoms and functioning ( rated by parents ) , and improvement in youth-rated symptoms . Increased skills alone were not associated with improvement , but patients of clinicians above the mean for both skill and patient-centeredness change improved most OBJECTIVE To describe the theoretical basis , use , and satisfaction with Teen CHAT , an online educational intervention design ed to improve physician-adolescent communication about healthy weight . METHODS Routine health maintenance encounters between pediatricians and family practitioners and their overweight adolescent patients were audio recorded , and content was coded to summarize adherence with motivational interviewing techniques . An online educational intervention was developed using constructs from social cognitive theory and using personalized audio recordings . Physicians were r and omized to the online intervention or not , and completed post-intervention surveys . RESULTS Forty-six physicians were recruited , and 22 physicians were r and omized to view the intervention website . The educational intervention took an average of 54min to complete , and most physicians thought it was useful , that they would use newly acquired skills with their patients , and would recommend it to others . Fewer physicians thought it helped them address confidentiality issues with their adolescent patients . CONCLUSION The Teen CHAT online intervention shows potential for enhancing physician motivational interviewing skills in an acceptable and time-efficient manner . PRACTICE IMPLICATION S If found to be effective in enhancing motivational interviewing skills and changing adolescent weight-related behaviors , wide dissemination will be feasible and indicated |
13,853 | 27,410,189 | None of the individual subgroup comparisons of aqueous chlorhexidine versus aqueous povidone-iodine , alcoholic chlorhexidine versus aqueous povidone-iodine and alcoholic chlorhexidine versus alcoholic povidone-iodine showed clear differences for catheter-related BSI or mortality ( and were generally underpowered ) .
AUTHORS ' CONCLUSIONS It is not clear whether cleaning the skin around CVC insertion sites with antiseptic reduces catheter related blood stream infection compared with no skin cleansing .
Skin cleansing with chlorhexidine solution may reduce rates of CRBSI and catheter colonisation compared with cleaning with povidone iodine .
Moreover these results may be influenced by the nature of the antiseptic solution ( i.e. aqueous or alcohol-based ) . | BACKGROUND The central venous catheter ( CVC ) is a device used for many functions , including monitoring haemodynamic indicators and administering intravenous medications , fluids , blood products and parenteral nutrition .
However , as a foreign object , it is susceptible to colonisation by micro-organisms , which may lead to catheter-related blood stream infection ( BSI ) and in turn , increased mortality , morbidities and health care costs .
OBJECTIVES To assess the effects of skin antisepsis as part of CVC care for reducing catheter-related BSIs , catheter colonisation , and patient mortality and morbidities . | OBJECTIVE To determine the effect of routine intravenous ( IV ) administration set changes on central venous catheter ( CVC ) colonization and catheter-related bacteremia . DESIGN Prospect i ve , r and omized , controlled trial . SETTING Eighteen-bed intensive care unit ( ICU ) in a large metropolitan hospital . PARTICIPANTS Two hundred fifty-one patients with 404 chlorhexidine gluconate and silver sulfadiazine-coated multi-lumen CVCs . INTERVENTIONS CVCs inserted in the ICU and in situ on day 4 were r and omized to have their IV administration sets changed on day 4 ( n = 203 ) or not at all ( n = 201 ) . Use of fluid containers and blood product administration sets was limited to 24 hours . CVCs were removed when not required , infection was suspected , or in place on day 7 . Catheter cultures were performed on removal by blinded laboratory staff . Catheter-related bacteremia was diagnosed by a blinded intensivist using strict definitions . Data were collected regarding catheter duration , site , Acute Physiology and Chronic Health Evaluation ( APACHE ) II score , patient age , diagnosis , hyperglycemia , hypoalbuminemia , immune status , number of fluid containers and IV injections , and administration of propofol , blood , total parenteral nutrition , or lipid infusion . RESULTS There were 10 colonized CVCs in the group receiving a set change and 19 in the group not receiving one . This difference was not statistically significant on Kaplan-Meier survival analysis . There were 3 cases of catheter-related bacteremia per group . Logistic regression found that burns diagnosis and increased ICU stay significantly predicted colonization . CONCLUSION IV administration sets can be used for 7 days in patients with short-term , antiseptic-coated CVCs In a prospect i ve study , 218 cardiothoracic patients , in whom ' Abbocath-T ' cannulae had been inserted preoperatively into the internal jugular vein , were r and omized to receive skin preparation of the insertion site with tincture of iodine ( 108 controls ) or tincture of iodine followed by application of sterile 2 % calcium mupirocin ointment ( 110 test patients ) . Cannulae were usually removed within 48 h of the operation . Patients receiving mupirocin were less likely to develop significant colonization of one or more of their cannulae as judged by Maki 's criterion of a yield of greater than 15 colony forming units ( cfu ) from a cannula segment rolled on an agar plate ( 17 % of mupirocin treated patients compared with 54 % of the controls , P less than 0.001 ) . Coagulase-negative staphylococci , micrococci , or both , were the commonest isolates and were cultured from 70 % of the 186 control cannulae compared with 24 % of 172 cannulae inserted through mupirocin-treated skin ( P less than 0.001 ) . A count of more than 15 cfu was found on the tips of 25 % control cannulae compared with 5 % of the cannulae from mupirocin-treated patients , an effect which was independent of in-situ time ( P less than 0.001 ) . For cannulae with colonized tips , the same species was isolated from the skin of the insertion site in 67 % , from the exterior of the hub in 61 % and from the lumen in only 15 % . There were no side effects attributed to mupirocin or superinfection with resistant organisms . We conclude that in cardiothoracic patients the application of mupirocin after st and ard skin preparation with tincture of iodine significantly reduces the colonization of central venous cannulae by organisms derived from the skin insertion site The objective of this study was to assess the risk of bacteremia , estimate the cost and evaluate the quality of life by using a transparent dressing ( TD ) versus ( vs ) a dry gauze ( DG ) on the exit site of long term central I.V. catheters ( LTCC ) of hemodialysis patients . This 6-months preliminary study was conducted on 58 patients ( pts ) r and omized to receive DG replaced 3 times/week ( 29 pts ) or TD replaced every 7 days ( 29 pts ) . Data on patients , conditions of the exit site , local infection , bacteremia , quality of life and cost related to each type of dressing were collected . Two pts in the DG group experienced bacteremia related to their LTCC vs 1 pt in the group TD . A total of 7 ( DG ) vs 13 ( TD ) pts experienced skin condition changes at the catheter exit site . Some skin reactions , erythema and pruritus , did occur initially in the group TD and was due in part to insufficient drying time of the skin preparation solution . The estimated individual , weekly costs for using the DG was $ 7.60 vs $ 4.72 Canadian dollars for the TD . The SF-36 ™ scores did not show a significant difference between the 2 groups during the study ( 3.8 ( PCS ) , 6.4 ( MCS ) at study end ) . Although this study was statistically underpowered , it suggests that the incidence of bacteremia was not increased with the use of a TD . Moreover , the use of a TD allowed fewer dressing changes , lowered total treatment costs , with no observed unfavorable impact on the quality of life and without significant local complications of the exit site . Based on the positive results observed in this pilot study , further study is warranted to examine the cost effectiveness of long-term use of TD dressings on dialysis catheter exit sites BACKGROUND Intravascular-catheter-related infections are frequent life-threatening events in health care , but incidence can be decreased by improvements in the quality of care . Optimisation of skin antisepsis is essential to prevent short-term catheter-related infections . We hypothesised that chlorhexidine-alcohol would be more effective than povidone iodine-alcohol as a skin antiseptic to prevent intravascular-catheter-related infections . METHODS In this open-label , r and omised controlled trial with a two-by-two factorial design , we enrolled consecutive adults ( age ≥18 years ) admitted to one of 11 French intensive-care units and requiring at least one of central -venous , haemodialysis , or arterial catheters . Before catheter insertion , we r and omly assigned ( 1:1:1:1 ) patients via a secure web-based r and om-number generator ( permuted blocks of eight , stratified by centre ) to have all intravascular catheters prepared with 2 % chlorhexidine-70 % isopropyl alcohol ( chlorhexidine-alcohol ) or 5 % povidone iodine-69 % ethanol ( povidone iodine-alcohol ) , with or without scrubbing of the skin with detergent before antiseptic application . Physicians and nurses were not masked to group assignment but microbiologists and outcome assessors were . The primary outcome was the incidence of catheter-related infections with chlorhexidine-alcohol versus povidone iodine-alcohol in the intention-to-treat population . This study is registered with Clinical Trials.gov , number NCT01629550 and is closed to new participants . FINDINGS Between Oct 26 , 2012 , and Feb 12 , 2014 , 2546 patients were eligible to participate in the study . We r and omly assigned 1181 patients ( 2547 catheters ) to chlorhexidine-alcohol ( 594 patients with scrubbing , 587 without ) and 1168 ( 2612 catheters ) to povidone iodine-alcohol ( 580 patients with scrubbing , 588 without ) . Chlorhexidine-alcohol was associated with lower incidence of catheter-related infections ( 0·28 vs 1·77 per 1000 catheter-days with povidone iodine-alcohol ; hazard ratio 0·15 , 95 % CI 0·05 - 0·41 ; p=0·0002 ) . Scrubbing was not associated with a significant difference in catheter colonisation ( p=0·3877 ) . No systemic adverse events were reported , but severe skin reactions occurred more frequently in those assigned to chlorhexidine-alcohol ( 27 [ 3 % ] patients vs seven [ 1 % ] with povidone iodine-alcohol ; p=0·0017 ) and led to chlorhexidine discontinuation in two patients . INTERPRETATION For skin antisepsis , chlorhexidine-alcohol provides greater protection against short-term catheter-related infections than does povidone iodine-alcohol and should be included in all bundles for prevention of intravascular catheter-related infections . FUNDING University Hospital of Poitiers , CareFusion OBJECTIVE To compare the effectiveness for prevention of central venous and arterial catheter colonization of 3 skin antisepsis with 1 of 3 antiseptic solutions : 10 % aqueous povidone iodine ( aqueous PI ) , 2 % aqueous chlorhexidine gluconate ( aqueous CG ) , and 0.5 % alcoholic chlorhexidine gluconate ( alcoholic CG ) . DESIGN Prospect i ve , r and omized controlled trial . SETTING Intensive care unit in a teaching hospital . METHODS Patients were r and omly assigned to 1 of the 3 skin antisepsis groups . The distal tips of catheters were semiquantitatively cultured when the catheters were no longer necessary or if there was a suspicion of catheter-related infection . Rates of catheter colonization , catheter-related sepsis , and catheter-related bacteremia were compared among the 3 groups . RESULTS A total of 631 catheters were included in the study ( 194 from the aqueous PI group , 211 from the aqueous CG group , and 226 from the alcoholic CG group ) . The incidence of catheter colonization was significantly lower in the alcoholic CG than in the aqueous PI group ( 14.2 % vs 24.7 % ; relative risk , 0.5 [ 95 % confidence interval , 0.3 - 0.8 ; P < .01 ] ) ; it was also significantly lower in the aqueous CG group than in the aqueous PI group ( 16.1 % vs 24.7 % ; relative risk , 0.6 [ 95 % confidence interval , 0.4 - 0.9 ; P = .03 ] ) . There were no significant differences between the aqueous CG and the alcoholic CG groups . Incidences of catheter-related bacteremia were similar for all 3 groups . The aqueous and alcoholic CG solutions were superior to the aqueous PI solution in preventing catheter colonization due to gram-positive bacteria . CONCLUSIONS The aqueous and alcoholic CG solutions for cutaneous antisepsis were similarly effective in preventing colonization of central venous catheters and arterial catheters . Both had significantly lower incidences of colonization than did the aqueous PI solution ; this effect seems to be related to the CG solutions ' more efficacious prevention of colonization with gram-positive bacteria OBJECTIVE To examine the extent to which US acute care hospitals have adopted recommended practice s to prevent central venous catheter-related bloodstream infections ( CR-BSIs ) . PARTICIPANTS AND METHODS Between March 16 , 2005 , and August 1 , 2005 , a survey of infection control coordinators was conducted at a national r and om sample of nonfederal hospitals with an intensive care unit and more than 50 hospital beds ( n=600 ) and at all Department of Veterans Affairs ( VA ) medical centers ( n=119 ) . Primary outcomes were regular use of 5 specific practice s and a composite approach for preventing CR-BSIs . RESULTS The overall survey response rate was 72 % ( n=516 ) . A higher percentage of VA compared to non-VA hospitals reported using maximal sterile barrier pre caution s ( 84 % vs 71 % ; P=.01 ) ; chlorhexidine gluconate for insertion site antisepsis ( 91 % vs 69 % ; P<.001 ) ; and a composite approach ( 62 % vs 44 % ; P=.003 ) combining concurrent use of maximal sterile barrier pre caution s , chlorhexidine gluconate , and avoidance of routine central line changes . Those hospitals having a higher safety culture score , having a certified infection control professional , and participating in an infection prevention collaborative were more likely to use CR-BSI prevention practice s. CONCLUSION Most US hospitals are using maximal sterile barrier pre caution s and chlorhexidine gluconate , 2 of the most strongly recommended practice s to prevent CR-BSIs . However , fewer than half of non-VA US hospitals reported concurrent use of maximal sterile barrier pre caution s , chlorhexidine gluconate , and avoidance of routine central line changes . Wider use of CR-BSI prevention practice s by hospitals could be encouraged by fostering a culture of safety , participating in infection prevention collaboratives , and promoting infection control professional certification BACKGROUND Long-term central venous catheterization is associated with a higher rate of catheter-related blood stream infections ( CR-BSI ) . It is unclear whether there is a difference in the CR-BSI rate associated with central venous catheters ( CVCs ) and peripherally inserted central catheters ( PICCs ) in long-stay patients in surgical intensive care units ( SICUs ) . We hypothesized that PICC use reduces the rate of CR-BSI compared with use of antiseptic CVCs in these patients . METHODS All 121 patients admitted to our SICU for ≥14 days between July 2005 and July 2006 were included . Central venous access was maintained with an antiseptic CVC ( Arrow Guard silver/chlorhexidine ; n = 263 ) or replacement with a PICC ( n = 37 ) . Experienced residents , using maximum barrier pre caution s and chlorhexidine skin preparation , placed central lines ; a credentialed registered nurse placed PICCs similarly . A CR-BSI was defined by semi-quantitative catheter tip cultures with ≥15 colony-forming units and at least one positive blood culture with the same organism . Multivariable regression was performed to identify predictors of CR-BSI . RESULTS There were 13 CVC infections and one PICC infection , result ing in an infection rate of 6.0/1,000 catheter-days for CVCs and 2.2/1,000 for PICCs . Infected and non-infected CVCs were in place a mean of 25 ± 11 and 16 ± 9 days , respectively . The infected PICC was in place for 19 days , whereas the remainder of the PICCs were in place a mean of 14 ± 17 days . Logistic regression demonstrated that line days ( duration of catheterization ) was the only independent predictor of CVC infection ( p = 0.015 ) . CONCLUSION In this non-r and omized study , PICC was associated with fewer CR-BSIs in long-stay SICU patients , although CVCs were in place longer than PICC lines . The only predictor of CVC infection was the duration the line was in place . These results suggest that minimizing the duration of central venous access and substituting PICC for CVC may reduce the incidence of CR-BSI in long-stay SICU patients The objective of the study was to evaluate the effectiveness of chlorhexidine-impregnated sponges for reducing catheter-related infections of central venous catheters inserted for cancer chemotherapy . The method used was a r and omized , prospect i ve , open , controlled clinical study ( three-step group sequential analysis protocol ) . The patients were from two high dependency units at a university hospital undergoing chemotherapy for haematological or oncological malignancies requiring central venous catheters ( CVCs ) expected to remain in place for at least 5 days . Six hundred and one patients with 9,731 catheterization days were studied between January 2004 and January 2006 . Patients admitted for chemotherapy received chlorhexidine and silver sulfadiazine-impregnated triple-lumen CVCs under st and ardized conditions and were r and omized to the groups receiving a chlorhexidine gluconate-impregnated wound dressing or a st and ard sterile dressing . Daily routine included clinical assessment of the insertion site ( swelling , pain , redness ) , temperature , white blood count and C-reactive protein . Catheters remained in place until they were no longer needed or when a CVC-related infection was suspected . Infection was confirmed with blood cultures via the catheter lumina and peripheral blood cultures according to the time-to-positivity method . Six hundred and one patients were included . The groups were comparable with respect to demographic and clinical data . The incidence of CVC-related infections were 11.3 % ( 34 of 301 ) and 6.3 % ( 19 of 300 ) in the control and chlorhexidine-impregnated wound dressing groups , respectively ( p = 0.016 , relative risk 0.54 ; confidence interval 0.31–0.94 ) . Especially , catheter-related infections at internal jugular vein insertions could be reduced ( p = 0.018 ) . No adverse effects related to the intervention were observed . The use of chlorhexidine-impregnated wound dressings significantly reduced the incidence of CVC-related infections in patients receiving chemotherapy Background Catheter-related infection is the third cause of infections in intensive care units ( ICU ) , increasing the length of stay in ICU and hospital , mortality , and costs . Skin antisepsis is one of the most prevalent preventive measures . In this respect , it would appear preferable to recommend the use of alcoholic povidone iodine or chlorhexidine rather than aqueous povidone iodine . However , the data comparing chlorhexidine to povidone-iodine , both of them in alcoholic solutions , remain limited . Moreover , the benefits of enhanced cleaning prior to disinfection of skin that is not visibly soiled have yet to be confirmed in a r and omized study . Methods A prospect i ve multicenter , 2 × 2 factorial , r and omized-controlled , assessor-blind trial will be conducted in 11 intensive care units in six French hospitals . All adult patients aged over 18 years requiring the insertion of at least one peripheral arterial catheter and /or a non-tunneled central venous catheter and /or a hemodialysis catheter and /or an arterial pulmonary catheter will be r and omly assigned to have all their catheters cared with one of four skin preparation strategies ( 2 % chlorhexidine/70 % isopropyl alcohol or 5 % povidone iodine/69 % ethanol with or without prior skin scrubbing ) . At catheter removal , catheter tips will be quantitatively cultured . Sets of aerobic and anaerobic blood cultures will be routinely obtained when a patient has fever , hypothermia , or other indications . In case of suspected catheter-related infection the patient ’s form will be review ed by an independent adjudication committee . We plan to enroll 2,400 patients ( 4,800 catheters ) . The main objective is to demonstrate that use of 2 % alcoholic chlorhexidine compared to 5 % alcoholic povidone iodine in skin preparation lowers the rate of catheter-related infection . The second endpoint is to demonstrate that enhanced skin cleaning prior to disinfection of skin that is not visibly soiled does not reduce catheter colonization . Other outcomes include comparison of skin colonization at catheter insertion site , comparison of catheter colonization and catheter-related bacteremia taking place during implementation of the four strategies of skin preparation , and cutaneous tolerance , length of hospitalization , mortality , and costs . Discussion This study will help to up date recommendations on the choice of an antiseptic agent to use in skin preparation prior to insertion of a vascular catheter and , by extension , of an epidural catheter and it will likewise help to up date recommendations on the usefulness of skin scrubbing prior to disinfection when the skin is not visibly soiled . Trial registration Clinical trials.gov number Background : Central venous ( CV ) catheters play an essential role in the management of critically ill patients in the Intensive Care Unit ( ICU ) . CV lines are , however , allied to catheter-associated blood stream infections . Bacterial colonization of CV lines is deemed the main cause of catheter-associated infection . The purpose of our study was to compare bacterial colony counts in the catheter site before CV line insertion in two groups of post-cardiac surgery patients : a group receiving Sanosil ( an antiseptic agent composed of H2O2 and silver ) and a control group . Methods : This interventional prospect i ve double-blinded clinical trial recruited the patients in three post-cardiac surgery ICUs of a heart center . The participants were divided into interventional ( 113 patients ) and control ( 136 patients ) groups . Sanosil was added to the routine preparation procedure ( Chlorhexidine bath one day before and scrub with Povidone-Iodine just before the CV line insertion ) . After the removal of the CV lines , the catheters tips were sent for culture and evaluation of colony counts . Results : Catheter colonization occurred in 55 ( 22.1 % ) patients : 26 ( 23 % ) patients in the Sanosil group and 29 ( 21.3 % ) in the control group ; there was no significant statistical difference between the two groups ( p value = 0.75 , RR = 1.05 , 95 % CI : 0.76–1.45 ) . The most common organism having colonized in the cultures of the catheter tips was staphylococcus epidermis : 20 cases in the control group and 16 cases in the intervention group . Conclusion : Catheter colonization frequently occurs in post-cardiac surgery patients . However , our results did not indicate the effectiveness of adding Sanosil to the routine preparation procedure with respect to reducing catheter bacterial colonization BACKGROUND Although chlorhexidine-based solutions and alcohol-based povidone-iodine have been shown to be more efficient than aqueous povidone-iodine for skin disinfection at catheter insertion sites , their abilities to reduce catheter-related infection have never been compared . METHODS Consecutively scheduled central venous catheters inserted into jugular or subclavian veins were r and omly assigned to be disinfected with 5 % povidone-iodine in 70 % ethanol or with a combination of 0.25 % chlorhexidine gluconate , 0.025 % benzalkonium chloride , and 4 % benzylic alcohol . Solutions were used for skin disinfection before catheter insertion ( 2 consecutive 30-second applications separated by a period sufficiently long to allow for dryness ) and then as single applications during subsequent dressing changes ( every 72 hours , or earlier if soiled or wet ) . RESULTS Of 538 catheters r and omized , 481 ( 89.4 % ) produced evaluable culture results . Compared with povidone-iodine , the chlorhexidine-based solution was associated with a 50 % decrease in the incidence of catheter colonization ( 11.6 % vs 22.2 % [ P = .002 ] ; incidence density , 9.7 vs 18.3 per 1000 catheter-days ) and with a trend toward lower rates of catheter-related bloodstream infection ( 1.7 % vs 4.2 % [ P = .09 ] ; incidence density , 1.4 vs 3.4 per 1000 catheter-days ) . Independent risk factors for catheter colonization were catheter insertion into the jugular vein ( adjusted relative risk , 2.01 ; 95 % confidence interval , 1.24 - 3.24 ) and use of povidone-iodine ( adjusted relative risk , 1.87 ; 95 % confidence interval , 1.18 - 2.96 ) . CONCLUSION Chlorhexidine-based solutions should be considered as a replacement for povidone-iodine ( including alcohol-based ) formulations in efforts to prevent catheter-related infection Objective : To investigate whether maximal sterile barrier pre caution s ( MSBPs ) during central venous catheter ( CVC ) insertion are truly effective in preventing catheter-related bloodstream infections ( CRBSIs ) in patients in general surgical units . Summary Background Data : The reported effectiveness of MSBPs was based on the results of a single-center r and omized controlled trial by Raad et al and the majority of the patients ( 99 % ) in the study were chemotherapy out patients . Methods : Between March 14 , 2004 and December 28 , 2006 , the patients scheduled for CVC insertion in surgical units at 9 medical centers in Japan were r and omly assigned to either an MSBP group ( n = 211 ) or a st and ard sterile barrier pre caution ( SSBP ) group ( n = 213 ) . This study was registered in the UMIN Clinical Trials Registry ( registration ID number : UMIN000001400 ) . Results : The median ( range ) duration of catheterization was 14 days ( 0–92 days ) in the MSBP group and 14 days ( 0–112 days ) in the SSBP group . There were 5 cases ( 2.4 % ) of CRBSI in the MSBP group and 6 cases ( 2.8 % ) in the SSBP group ( relative risk , 0.84 ; 95 % confidence interval , 0.26–2.7 ; P = 0.77 ) . The rate of CRBSIs per 1000 catheter days was 1.5 in the MSBP group and 1.6 in the SSBP group . There were 8 cases ( 3.8 % ) of catheter-related infections in the MSBP group and 7 cases ( 3.3 % ) in the SSBP group ( relative risk , 1.2 ; 95 % confidence interval , 0.43–3.1 ; P = 0.78 ) . The rate of catheter-related infection per 1000 catheter days was 2.4 in the MSBP group and 1.9 in the SSBP group . Conclusions : This study is larger in sample size than the one performed by Raad et al and could not demonstrate better prevention of CRBSIs by MSBP compared with SSBP . A large r and omized controlled trial or at least a meta- analysis of any other studies in the literature is necessary to reach to a conclusion on this issue Background : The r and omized two-way factorial Dressing Study ( 1,636 patients , 28,931 catheter days ) showed that a chlorhexidine-impregnated sponge decreased the incidence of major catheter-related infections from 1.4‰ to 0.6‰ catheter days , and that scheduled dressing changes every 7 days was not inferior to scheduled changes every 3 days . Here , we assessed the cost benefits of chlorhexidine-impregnated sponge use . Methods : Costs directly related to major catheter-related infections and the costs of chlorhexidine-impregnated sponge and contact dermatitis were calculated prospect ively using microcosting methods during the original study . The added length of stay in the intensive care unit due to major catheter-related infection was estimated using the disability model and assuming a cost of $ 2,118/intensive care unit day . The cost of each strategy was estimated based on all costs and on the probability of major catheter-related infection according to the Dressing Study results . Interventions : None . Results : Median direct cost of major catheter-related infection was $ 792 . Estimated added length of stay due to major catheter-related infection was 11 days ( 95 % confidence interval [ −2 days ; 26 days ] ) . Overall cost of major catheter-related infection was $ 24,090/episode . Each dressing cost $ 9.08 ( 146 observations ) and each chlorhexidine-impregnated sponge cost $ 9.73 . Assuming a baseline major catheter-related infection incidence of 1.4‰ catheter days , chlorhexidine-impregnated sponge use saved $ 197 per patient with the 3-day chlorhexidine-impregnated sponge dressing change strategy , and $ 83 with the 7-day st and ard dressing change strategy . Chlorhexidine-impregnated sponge use remained cost saving assuming a baseline major catheter-related infection incidence as low as 0.35‰ catheter days , or an overall cost per major catheter-related infections of up to $ 4,400 . Conclusion : Chlorhexidine-impregnated sponge for arterial and central venous catheters saves money by preventing major catheter-related infections , even in intensive care units with low baseline major catheter-related infection levels . Trial Registration : Clinical trials.gov number , NCT00417235 OBJECTIVES To characterize and enumerate central venous catheter (CVC)-related complications among children with chronic illnesses , and to reduce the complication rate through changes in CVC management and education . DESIGN A prospect i ve observational study followed by an educational program and a nonr and omized interventional trial . SETTING The Children 's Hospital of Philadelphia , a tertiary , pediatric facility . PATIENTS 268 children with Broviac , Hickman , or Infusaport catheters in place during 58,290 catheter days . INTERVENTIONS Development and implementation of protocol s for cleaning insertion site and hub , use of nonocclusive dressings , and manipulation of access ; formal staff and parental education about protocol s. RESULTS CVC-related infections fell from 4.58/1,000 catheter-days preintervention to 3.83 postintervention ( risk ratio [ RR ] , 0.20 ; 95 % confidence interval [ CI95 ] , 0.89 - 1.622 ; P = .25 ) ; exit-site infections fell from 0.58 to 0.11 ( CI95 , 1.22 - 45.64 ; P = .02 ) ; rates among infants on the surgical service fell from 15.46 to 6.67 ( RR , 2.31 ; CI95 , 1.10 - 4.30 ; P = .02 ) . CONCLUSIONS Education and changes in management protocol s reduced the incidence of exit-site infections among all patients and reduced the overall infectious complication rate among the infants receiving parenteral nutrition on the surgical service . Other interventions are needed to decrease further the infectious complications in these children AIM Intravenous catheters have become one of the essential tools of modern medicine . Preventive measures taken while the catheter is being inserted or in place can provide a significant reduction in catheter-related infections and bacteremia/sepsis . This study aims to evaluate whether the patient 's age and gender , the presence of malignancy and coexisting diseases , catheter duration , use of total parenteral nutrition solution , blood products , and antibiotics as well as antiseptics applied while attaching the central venous catheter ( chlorhexidine and povidone-iodine ) affect the development of catheter colonization and catheter-related bloodstream infections in patients with central venous catheters . MATERIAL S AND METHODS Our study includes 50 cases which were admitted to İzmir Atatürk Training and Research Hospital , I. Surgical Clinic , hospitalized due to various reasons between the date s of January‒December 2010 and required catheter use . Patients were r and omly assigned to one of the two operating rooms , in one of which the insertion site was disinfected with Poviiodeks ® ( 10 % povidone-iodine ) while in the other , ( latter ) Savlosol ® ( 15 % cetrimide , 1.5 % Chlorhexidine-gluconate , ethanol ) was used . RESULTS Among many factors examined in our study , only the use of clorhexidine versus iodine povidon in skin antisepsis was found to be statistically significant in the reduction of CRBSI and CC ( for CRBSI p=0.022 and for CC p=0.047 ) . CONCLUSIONS Our study concludes that skin antisepsis is the only determining factor in the prevention of blood infection and colonization due to central venous catheter application and the use of clorhexidine vs. povidon is proven to be statistically significant ( Tab . 1 , Ref . 27 ) BACKGROUND Catheter-related bloodstream infections ( CRBSIs ) account for the majority of hemodialysis-related infections . There are no published data on the efficacy of the chlorhexidine-impregnated foam dressing at reducing the rate of CRBSI among patients undergoing hemodialysis . DESIGN A prospect i ve , nonblinded , crossover intervention trial to determine the efficacy of a chlorhexidine-impregnated foam dressing to reduce the rate of CRBSI among patients undergoing hemodialysis . SETTING Two outpatient dialysis centers . PATIENTS A total of 121 patients who underwent dialysis through tunneled central venous catheters received the intervention during the trial . METHODS The primary outcome of interest was the incidence of CRBSI . A nested cohort study of all patients who received the chlorhexidine-impregnated foam dressing was also conducted . Backward stepwise logistic regression analysis was used to determine independent risk factors for development of CRBSI . RESULTS Thirty-seven CRBSIs occurred in the intervention group , for an incidence of 6.3 CRBSIs per 1,000 dialysis sessions , and 30 CRBSIs occurred in the control group , an incidence of 5.2 CRBSIs per 1,000 dialysis sessions ( risk ratio , 1.22 [ 95 % confidence interval { CI } , 0.75 - 1.97 ] ; P = .46 ) . The chlorhexidine-impregnated foam dressing was well tolerated , with only 2 patients ( < 2 % ) experiencing dermatitis that led to its discontinuation . The only independent risk factor for development of CRBSI was dialysis treatment at one dialysis center ( adjusted odds ratio , 4.4 [ 95 % CI , 1.77 - 13.65 ] ; P = .002 ) . Age of at least 60 years ( adjusted odds ratio , 0.28 [ 95 % CI , 0.09 - 0.82 ] ; P = .02 ) was associated with lower risk of CRBSI . CONCLUSIONS The use of a chlorhexidine-impregnated foam dressing did not decrease the incidence of CRBSI among patients with tunneled central venous catheters who were undergoing hemodialysis The clinical usefulness of hemodialysis catheters is limited by increased infectious morbidity and mortality . Topical antiseptic agents , such as mupirocin , are effective at reducing this risk but have been reported to select for antibiotic-resistant strains . The aim of the present study was to determine the efficacy and the safety of exit-site application of a st and ardized antibacterial honey versus mupirocin in preventing catheter-associated infections . A r and omized , controlled trial was performed comparing the effect of thrice-weekly exit-site application of Medihoney versus mupirocin on infection rates in patients who were receiving hemodialysis via tunneled , cuffed central venous catheters . A total of 101 patients were enrolled . The incidences of catheter-associated bacteremias in honey-treated ( n = 51 ) and mupirocin-treated ( n = 50 ) patients were comparable ( 0.97 versus 0.85 episodes per 1000 catheter-days , respectively ; NS ) . On Cox proportional hazards model analysis , the use of honey was not significantly associated with bacteremia-free survival ( unadjusted hazard ratio , 0.94 ; 95 % confidence interval , 0.27 to 3.24 ; P = 0.92 ) . No exit-site infections occurred . During the study period , 2 % of staphylococcal isolates within the hospital were mupirocin resistant . Thrice-weekly application of st and ardized antibacterial honey to hemodialysis catheter exit sites was safe , cheap , and effective and result ed in a comparable rate of catheter-associated infection to that obtained with mupirocin ( although the study was not adequately powered to assess therapeutic equivalence ) . The effectiveness of honey against antibiotic-resistant microorganisms and its low likelihood of selecting for further resistant strains suggest that this agent may represent a satisfactory alternative means of chemoprophylaxis in patients with central venous catheters OBJECTIVE To evaluate the incidence of nosocomial bacteremias related to the use of non-impregnated central venous catheters ( CVCs ) when only non-technologic strategies were used to prevent them . DESIGN This was a prospect i ve study of infectious complications of CVCs placed in intensive care unit ( ICU ) patients from April 1997 to December 2001 . SETTING The medical-surgical ICU of a tertiary-care , university-affiliated hospital in Argentina . METHODS We studied all patients admitted to the ICU using non-impregnated CVCs . Maximal sterile barrier pre caution s ( ie , use of cap , mask , sterile gown , sterile gloves , and large sterile drape ) , strict h and washing , preparation of the patients ' skin with antiseptic solutions , insertion and management of catheters by trained personnel , and continuing quality improvement programs aim ed at appropriate insertion and maintenance of catheters were employed . RESULTS During the study period , 2,525 patients were admitted to the ICU . Eight hundred sixty-eight patients had 1,037 CVCs inserted . The number of CVC-related bloodstream infections ( BSIs ) , acquired in the ICU , was 2.7 per 1,000 CVC-days ( 13 nosocomial CVC-related BSIs during 4,770 days of CVC use ) . Microorganisms isolated included methicillin-susceptible Staphylococcus aureus ( n = 6 ) , methicillin-resistant S. aureus ( n = 2 ) , coagulase-negative methicillin-resistant Staphylococcus ( n = 2 ) , Escherichia coli ( n = 1 ) , Klebsiella pneumoniae ( n = 1 ) , and Enterobacter cloacae ( n = 1 ) . CONCLUSIONS A low rate of catheter-related BSI was achieved without antimicrobial-impregnated catheters . The incidence of CVC-associated bacteremias corresponded to the 10th to 20th percentile range of the National Nosocomial Infections Surveillance System hospitals for the same type of ICU OBJECTIVES To compare the costs with the benefits of using chlorhexidine gluconate dressings on central venous catheters and to determine the effectiveness of these dressings in reducing local infections and catheter-related bloodstream infections ( CRBSIs ) , costs , and mortality . DESIGN Cost-benefit analysis using r and omized , controlled trial data on chlorhexidine dressing prevention of local infection and CRBSI , data on cost of chlorhexidine dressing versus st and ard treatment , data on averted cost of treating local infection and CRBSI , and data on mortality attributable to CRBSI . Decision analysis evaluated averted CRBSI treatment cost per patient result ing from chlorhexidine dressing use . Sensitivity analyses demonstrated net benefit of chlorhexidine dressing , varying baseline rate of CRBSI , incremental cost of treating CRBSI , and number of catheters , and evaluated mortality preventable through chlorhexidine dressing use , varying baseline rate of CRBSI , number of catheters , and mortality attributable to CRBSI . PATIENTS AND SETTING Patients of all Philadelphia area hospitals and one Philadelphia academic medical center . RESULTS Estimated potential annual U.S. net benefits from chlorhexidine dressing use ranged from $ 275 million to approximately $ 1.97 billion . Cost-benefit findings persisted in sensitivity analyses varying baseline rate of CRBSI , incremental cost of treating CRBSI , and overall number of catheters used . Preventable mortality analyses showed potential decreases of between 329 and 3,906 U.S. deaths annually as a result of nationwide use of chlorhexidine dressing . CONCLUSIONS Chlorhexidine dressings would reduce costs , local infections and CRBSIs , and deaths . Use of chlorhexidine dressings should be considered to prevent infections among patients with catheters Objective : To measure systemic silver absorption when using silver-impregnated alginate central catheter dressings in very low birth weight ( VLBW ) neonates and to monitor blood stream infection . Study Design : Fifty infants were enrolled in a prospect i ve , r and omized controlled trial lasting 28 days . Each patient was assigned to st and ard dressing or silver alginate ( Algidex ) group . Serum silver concentrations were obtained on day 1 , 7 , and 28 . Result : Significant differences in mean serum silver concentrations for the treatment versus st and ard dressing group were observed using student ’s t-test analysis . The silver alginate group had a 45.8 % reduction in infection/1000 line days , although too few patients were enrolled to draw meaningful efficacy conclusions about prevention of blood stream infection . Conclusion : Mean serum silver concentrations in the treatment group were significantly higher than controls although below levels anticipated to result in toxicity . A large study evaluating reduced blood stream infections in VLBW infants is warranted A prospect i ve cohort study was performed to evaluate the influence of catheter manipulations on catheter associated bloodstream infection ( CABSI ) in neonates . Neonates admitted between 1 November 1993 and 31 October 1994 at the neonatal intensive care unit of a university hospital were included in the study . Seventeen episodes of CABSI occurred in 357 central catheters over a period of 3470 catheter-days , with a cumulative incidence of 4.7/100 catheters and an incidence density of 4.9/1000 catheter-days . Patient and catheter-related risk factors independently associated with CABSI were : catheter hub colonization ( odds ratio [ OR ] = 32.6 , 95 % confidence interval [ 95 % CI ] = 4.3 - 249 ) , extremely low weight ( < /= 1000 gram ) at time of catheter insertion ( OR = 9.1 , 95 % CI = 1.9 - 42.2 ) . Catheter manipulations independently associated with CABSI were disinfection of the catheter hub ( OR = 1.2 , 95 % CI = 1.1 - 1.3 ) , blood sampling ( OR = 1.4 , 95 % CI = 1.1 - 1.8 ) , heparinization ( OR = 0.9 , 95 % CI = 0.8 - 1.0 ) and antisepsis of exit site ( OR = 0.9 , 95 % CI = 0.8 - 1.0 ) . This study indicates that certain manipulations ( e.g. blood sampling through the central line ) and disconnection of the central venous catheter , which necessitates disinfection of the catheter hub , increase the risk of CABSI , while other procedures ( e.g. heparinization and exit site antisepsis ) , protect against CABSI in neonates BACKGROUND We sought to determine the long-term impact of " bundled " infection control interventions on the rates of catheter-associated bloodstream infection ( CA-BSI ) in a middle-income country . SETTING A 500-bed tertiary care center in Thail and . METHODS A 3-year , hospital-wide , prospect i ve quasi-experimental study was conducted for 1 year before the intervention ( period 1 ) , 1 year after implementation of the CA-BSI bundle ( period 2 ) , and at a 1-year follow-up after the intervention with intensified h and hygiene promotion ( period 3 ) . RESULTS In period 1 , 88 episodes of CA-BSI ( 14 cases per 1000 catheter-days ) were recorded . During period 2 , the CA-BSI rate decreased by 54.1 % ( 6.4 cases per 1000 catheter-days ; P < .001 ) . Compared with period 1 ( 8 % adherence ) , h and hygiene adherence was improved in period 2 ( 24 % ; P < .001 ) and period 3 ( 54 % ; P < .001 ) . The CA-BSI rate was further decreased by 78 % ( 1.4 cases per 1000 catheter-days ; P < .001 ) during period 3 . Notably , no CA-BSIs were seen in 6 of the 12 months ( 50 % ) of period 3 . Compared with period 1 , the mean number of catheter-days was significantly reduced in period 2 ( 4.9 + /- 1.5 days ; P < .001 ) and period 3 ( 4.1 + /- 1.1 days ; P < .001 ) . CONCLUSION Bundled infection control practice s are feasible and effective in sustaining reduced incidence of CA-BSI in patients with central venous catheters in a re source -limited setting A pilot r and omized trial in 3 Irish outpatient hemodialysis units compared 2 % chlorhexidine gluconate ( CHG ) in 70 % isopropyl alcohol with routinely used CHG solutions for central venous catheter exit site antisepsis . We found no significant difference between the groups for the prevention of catheter-related bloodstream infections ( 1/53 vs 2/52 ; relative risk [ RR ] , 0.49 ; 95 % confidence interval [ CI ] , 0.05 - 5.25 ; P = .55 ) and catheter-associated bloodstream infections ( 1/53 vs 4/52 ; RR , 0.25 ; 95 % CI , 0.03 - 2.12 ; P = .16 ) Objectives : To study the impact of a teaching intervention on the rate of central venous catheter-related bloodstream infections ( CRBSI ) in intensive care patients . Design : Prospect i ve before/after interventional cohort study on medical and surgical intensive care units . Setting : University hospital with five adult intensive care units . Patients : All patients with a central venous catheter on the five ICUs from September to December 2003 ( baseline period ) and from March to July 2004 ( intervention period ) . Interventions : Educational program with teaching of h and hygiene , st and ards of catheter care , and preparation of intravenous drugs . Measurements and Main Results : The primary outcome variable was the rate of CRBSIs per 1000 catheter days during a baseline period of 4 months and an intervention period of 5 months . The secondary outcome variable was compliance with h and hygiene . Of the patients , 499 patients with 6200 catheter days in the baseline period and 500 patients with 7279 catheter days were monitored in the intervention period . The incidence density of CRBSI decreased from 3.9 per 1000 catheter days in the preintervention phase to 1.0 per 1000 catheter days in the intervention phase ( p < 0.001 ) . The risk for CRBSI was significantly higher in the baseline period in both univariate and multivariate analysis . Other independent risk factors were hospitalization in the medical ICU and male gender . Time to CRBSI was significantly longer in the intervention period ( median 9 days vs. 6.5 days , respectively ; p = 0.02 ) . Compliance with h and hygiene improved slightly from 59 % in the baseline period to 65 % in the intervention period , but the rate of correct performance of the practice increased from 22.5 % to 42.6 % ( p = 0.003 ) . Conclusions : Evidence -based catheter-care procedures , guided by healthcare workers ' perceptions and including bedside teaching , reduce significantly the CRBSI rate and demonstrate that improving catheter care has a major impact on its prevention To investigate whether institution of maximal sterile barrier pre caution s ( SBPs ) during arterial catheter ( AC ) insertion prevents catheter colonization , as is the case for central venous catheters ( CVCs ) , a r and omized study was conducted . Three hundred seventy-three patients in whom a radial or dorsalis pedis AC was going to be inserted were r and omized to an SBP group or a st and ard-of-care group . These patients , in addition to all patients who were admitted to the unit with an AC already in place or who were not eligible for the r and omized study , were observed for AC-related colonization and infection . Data for 272 r and omized patients were available for analysis . The colonization incidence was 20.2 cases per 1000 catheter-days in the SBP group and 15.8 cases per 1000 catheter-days in the control group ( P>.1 ) . AC-related infection occurred in 3 patients in the SBP group and in 7 patients in the control group ( P>.1 ) . Five episodes of AC-related bloodstream infection were diagnosed ( 1.5 cases per 1000 catheter-days ) . Use of SBPs did not prevent AC colonization or infection . The incidence of AC-related infectious complications was comparable to the incidence of CVC-related infection reported in the literature Abstract . Background : We investigated the efficacy of two commercially available , alcohol-based antiseptic solutions in decontaminating the insertion site of central lines . One solution contained the bispyridine octenidine dihydrochloride . Patients and Methods : In patients receiving either a central venous catheter ( CVC ) or a peripherally inserted central catheter ( PICC ) were alternately assigned to different skin disinfection regimens at the insertion site : ( A ) 0.1 % octendine dihydrochloride with 30 % 1-propanol and 45 % 2-propanol , ( B ) 74 % ethanol with 10 % 2-propanol . Quantitative skin cultures were obtained from the insertion site at predetermined intervals . Results : A total of 60 patients received 12 CVCs and 47 PICCs ( no significant difference with respect to gender , age and catheter type ) . In total , 90 cultures were assessed in each group . The median colony-forming unit ( cfu ) counts per 24 cm2 ( group A vs B ) were 2,270 vs 2,950 before , 20 vs 40 following and 860 vs 1,210 24 h after catheter insertion , respectively . A statistically significant difference in the efficacy of skin decontamination was seen between groups in culture set ( 3 ) and in the difference between culture sets ( 2 ) and ( 3 ) ( Wilcoxon rank sum test ) . Conclusion : Octenidine/propanol appears to be more effective than alcohol ( ethanol/propanol ) alone in reducing microflora of the skin at the PICC/CVC insertion site over a 24-h period Needleless connectors are being increasingly used for direct access to intravascular catheters . However , the potential for microbial contamination of these devices and subsequent infection risk is still widely debated . In this study the microbial contamination rate associated with three-way stopcock luers with st and ard caps attached was compared to those with Y-type extension set luers with Clearlink needleless connectors attached . Fifty patients undergoing cardiothoracic surgery who required a central venous catheter ( CVC ) as part of their peri- and postoperative management were studied for microbial contamination of CVC luers following 72 hrs in situ . Each patient 's CVC was r and omly design ated to have either the three-way stopcocks with caps ( control patients ) or Clearlink Y-type extension sets ( test patients ) . Prior to , and following each manipulation of the three-way stopcock luers or Clearlink devices , a 70 % ( v/v ) isopropyl alcohol swab was used for disinfection of the connections . The microbial contamination of 393 luers , 200 with st and ard caps and 193 with Clearlink attached , was determined . The internal surfaces of 20 of 200 ( 10 % ) three-way stopcock luers with st and ard caps were contaminated with micro-organisms whereas only one of 193 ( 0.5 % ) luers with Clearlink attached was contaminated ( P<0.0001 ) . These results demonstrate that the use of the Clearlink device with a dedicated disinfection regimen reduces the internal microbial contamination rate of CVC luers compared with st and ard caps . The use of such needle-free devices may therefore reduce the intraluminal risk of catheter-related bloodstream infection and thereby supplement current preventive guidelines The objectives of this study were to determine the risk factors associated with nosocomial infection ( NI ) in the intensive-care unit and to assess the influence of a h and -washing promotion programme on the NI rate . Over a 6-month study period ( P1 ) , a prospect i ve study of NI cases was performed , and risk factors for NI were analysed . Data were compared with those corresponding to a second period ( P2 ) , during which a health workers ' h and -washing promotion programme was carried out ; alcohol-based solution was also placed at the patients ' headboard . Eight hundred and six patients were included ( 395 patients in P1 and 411 in P2 ) . The mean APACHE II score was 11.41 ; there were no statistically significant differences in epidemiological or clinical variables between P1 and P2 , and there were no differences in risk factors for NI . The rate of infection in P1 was 26 % , and that in P2 was 16 % ( p < 0.05 ) . The h and -washing rate was higher in P2 than in P1 ( before patient care , 45 % and 35 % , respectively ; after contact with the patient , 63 % and 51 % , respectively ) . In the multivariate analysis , only central venous catheterization ( > 5 days ) and tracheostomy were statistically significant risk factors for NI ; having been included in the study during P1 or P2 was not statistically associated with NI . In conclusion , there was a significant increase in h and -washing frequency in P2 ; the incidence of NI during P1 was significantly higher than during P2 , but having been included in the study in P1 was not significantly associated with a higher rate of NI ; only central venous catheterization ( > 5 days ) and tracheostomy were significantly associated with NI The effect on the rate of central venous catheter sepsis of incorporating the catheter hub in a povidone-iodine ( Betadine ) connection shield was evaluated in a r and omized controlled clinical trial involving 47 Silastic catheters inserted in 35 patients solely for the administration of parenteral nutrition . All catheters were tunneled subcutaneously and once inserted were r and omized to one of two subsequent management groups . Group 1 ( n = 25 ) were managed in a st and ard fashion whereas Group 2 catheters ( n = 22 ) in addition were managed by incorporating the catheter hub in a Betadine connection shield ( Connection Shield 3 ; Travenol/Baxter ) . The catheter lifespans in the two groups were similar ( Group 1 mean 10.8 days ; range 3 - 28 : Group 2 mean 13.3 days : range 5 - 31 ) . There was a significant difference in the rates of both clinical sepsis ( Group 1 , 8 cases ; 32 % ; Group 2 , 1 case ; 4.5 % ; p less than 0.05 ) and bacteriologic sepsis ( Group 1 , 6 cases ; 24 % ; Group 2 , 0 cases ; p less than 0.05 ) in the two groups . Incorporating the catheter hub in a Betadine connection shield confers significant benefit in terms of reducing the incidence of catheter sepsis in patients receiving total parenteral nutrition BACKGROUND There are limited data from prospect i ve studies to indicate whether improvement in h and hygiene associated with the use of alcohol-based h and hygiene products results in improved patient outcomes . DESIGN A 2-year , prospect i ve , controlled , cross-over trial of alcohol-based h and gel . SETTING The study was conducted in 2 medical-surgical ICUs for adults , each with 12 beds , from August 2001 to September 2003 at a university-associated , tertiary care teaching hospital . METHODS An alcohol-based h and gel was provided in one critical care unit and not provided in the other . After 1 year , the assignment was reversed . The h and hygiene adherence rate and the incidence of nosocomial infection were monitored . Sample s for culture were obtained from nurses ' h and s every 2 months . RESULTS During 17,994 minutes of observation , which included 3,678 opportunities for h and hygiene , adherence rates improved dramatically after the introduction of h and gel , increasing from 37 % to 68 % in one unit and from 38 % to 69 % in the other unit ( P < .001 ) . Improvement was observed among all groups of healthcare workers . H and hygiene rates were better at higher workloads when h and gel was available in the unit ( P= .02 ) . No substantial change in the rates of device-associated infection , infection due to multidrug-resistant pathogens , or infection due to Clostridium difficile was observed . Culture of sample s from the h and s of nursing staff revealed that an increased number of microbes and an increased number of microbe species was associated with longer fingernails ( ie , more than 2 mm long ) , the wearing of rings , and /or lack of access to h and gel . CONCLUSIONS The introduction of alcohol-based gel result ed in a significant and sustained improvement in the rate of h and hygiene adherence . Fingernail length greater than 2 mm , wearing rings , and lack of access to h and gel were associated with increased microbial carriage on the h and s. This improvement in the h and hygiene adherence rate was not associated with detectable changes in the incidence of healthcare-associated infection BACKGROUND This study was undertaken to determine the frequency of skin colonization , hub colonization , and central venous catheter colonization in transparent hydrocolloid versus st and ard polyurethane dressings . METHODS Adult patients requiring the insertion of a multilumen central venous catheter in an intensive care unit were r and omized to receive either a st and ard polyurethane dressing or a transparent hydrocolloid dressing . Cultures were obtained from 125 skin insertion sites , 141 catheter hubs , 128 catheter tips , and blood sample s from 132 patients . Extensive data on patient and catheter characteristics were collected . RESULTS Skin and hub cultures revealed no significant difference in degree of colonization . However , the hydrocolloid group had a significantly higher level of catheter colonization than the polyurethane group ( P = .048 ) . Conversely , there was a significantly higher frequency of positive blood cultures in the polyurethane group ( P = .03 ) , although the majority were considered to be potential contaminants . There were only 6 cases in which the same species was simultaneously isolated from a positive blood culture and a colonized catheter , 5 from the hydrocolloid group and 1 from the polyurethane group . CONCLUSIONS The results of this study suggest that an increased risk of catheter colonization is associated with the use of hydrocolloid dressings , despite previous research suggesting that they significantly reduce microbial growth compared with st and ard polyurethane . The clinical significance of increased numbers of positive blood cultures in the polyurethane group requires further examination , although distinguishing between contamination and true infection in intensive care setting s continues to be method ologically challenging . Further studies are required to determine whether these findings are generalizable across different study setting s and whether similar outcomes are obtained when different br and s of hydrocolloid dressing are used OBJECTIVE In many hospitals , the only sterile pre caution s used during the insertion of a nontunneled central venous catheter are sterile gloves and small sterile drapes . We investigated whether the use of maximal sterile barrier ( consisting of mask , cap , sterile gloves , gown , and large drape ) would lower the risk of acquiring catheter-related infections . DESIGN Prospect i ve r and omized trial . SETTING A 500-bed cancer referral center . METHODS We r and omized patients to have their nontunneled central catheter inserted under maximal sterile barrier pre caution s or control pre caution s ( sterile gloves and small drape only ) . All patients were followed for 3 months postinsertion or until the catheter was removed , whichever came first . Catheter-related infections were diagnosed by quantitative catheter cultures and /or simultaneous quantitative blood cultures . RESULTS The 176 patients whose catheters were inserted by using maximal sterile barrier pre caution s were comparable to the 167 control patients in underlying disease , degree of immuno-suppression , therapeutic interventions , and catheter risk factors for infections ( duration and site of catheterization , number of catheter lumen , catheter insertion difficulty , reason for catheter removal ) . There were a total of four catheter infections in the test group and 12 in the control group ( P = 0.03 , chi-square test ) . The catheter-related septicemia rate was 6.3 times higher in the control group ( P = 0.06 , Fisher 's exact test ) . Most ( 67 % ) of the catheter infections in the control group occurred during the first 2 months after insertion , whereas 25 % of the catheter infections in the maximal sterile pre caution s group occurred during the same period ( P < 0.01 , Fisher 's exact test ) . Cost-benefit analysis showed the use of such pre caution s to be highly cost-effective . CONCLUSION Maximal sterile barrier pre caution s during the insertion of nontunneled catheters reduce the risk of catheter infection . This practice is cost-effective and is consistent with the practice of universal pre caution s during an invasive procedure Background : Infections of short term , nontunneled , intravascular catheters are often caused by migration of organisms from the insertion site . The aim of this study was to evaluate the effectiveness and safety of a chlorhexidine gluconate-impregnated dressing for the reduction of central venous catheter ( CVC ) colonization and CVC-associated bloodstream infections in infants and children after cardiac surgery . Methods : This prospect i ve , r and omized , controlled study was conducted in the pediatric cardiac intensive care unit of a tertiary care pediatric medical center . Patients 0–18 years of age who were admitted to the pediatric cardiac intensive care unit during a 14-month period and required a CVC for > 48 hours were r and omized to receive a transparent polyurethane insertion site dressing ( control group ) or a chlorhexidine gluconate-impregnated sponge ( Biopatch ) dressing covered by a transparent polyurethane dressing ( study group ) . The main outcome measures were rates of bacterial colonization , rates of CVC-associated bloodstream infections and adverse events . Results : Seventy-one patients were r and omized to the control group and 74 to the study group . There were no significant between group differences in age , sex , Pediatric Risk of Mortality score or cardiac severity score . CVC colonization occurred in 21 control patients ( 29 % ) and 11 ( 14.8 % ) study patients ( P = 0.0446 ; relative risk , 0.6166 ; 95 % confidence interval , 0.3716–1.023 ) . Bloodstream infection occurred in 3 patients ( 4.2 % ) in the control group and 4 patients ( 5.4 % ) in the study group . Local redness was noted in 1 control patient and 4 study group patients . Conclusions : The chlorhexidine gluconate-impregnated sponge is safe and significantly reduces the rates of CVC colonization in infants and children after cardiac surgery AIM The purpose of this prospect i ve , r and omized , controlled study was the comparison of maximal sterile barrier ( consisting of mask , cap , sterile gloves , gown , large drape ) vs control pre caution s ( mask , cap , sterile gloves , small drape ) and of transparent polyurethan film vs gauze dressing for use on central venous ( CVC ) nontunneled catheters , inserted via the jugular vein . Skin colonization at the insertion site ( defined by quantitative skin cultures performed at the time of insertion and in days 2 and 5 ) was used as a primary endpoint . Catheter tip colonization was also assessed through qualitative culture and CVC related sepsis was defined by the isolation of the same organism from the catheter tip and the blood , with clinical sepsis of no other apparent source . METHODS Eighty-two consecutive patients were enrolled , admitted to a mixed medical-surgical ICU , aged 72+/-12 years , 58 % male , SAPS II 42+/-13 . One-hundred and seven CVCs were studied ( presenting 750 catheter in situ days ) ; CVCs were in place for a mean period of 6.9+/-4.7 days and 5 episodes of central catheter-related bloodstream infection were detected ( 6.6 per 1000 catheter days ) . RESULTS A multiple logistic regression detected an increased risk of skin colonization in male gender ( OR=2.5 ) and control pre caution s ( OR=3.4 ) and no difference with regard to age , dressing and diagnostic group . CONCLUSIONS Maximal sterile barrier proved to be an effective and recommended practice . However surveillance skin cultures revealed the common and changing nature of colonization of skin at the insertion site Objective Central venous catheter (CVC)-related infections may be caused by micro-organisms introduced from the skin surface into deeper tissue at the time of CVC insertion . The optimal disinfection regimen to avoid catheter-related infections has not yet been defined . This study compares three different approaches . Design Prospect i ve r and omised trial . Setting A tertiary care hospital . Patients and participants One hundred nineteen patients scheduled electively to receive 140 CVCs . Interventions Skin disinfection was performed with either povidone-iodine 10 % ( PVP-iodine ) , chlorhexidine 0.5%/propanol 70 % , or chlorhexidine 0.5%/propanol 70 % followed by PVP-iodine 10 % . Prior to disinfection , a swab from the site of insertion was taken for culture . CVCs were removed if no longer needed or infection was suspected . All catheters were cultured quantitatively after removal . Measurement and results Bacteria could be isolated from 20.7 % of the catheter tips . Bacterial growth was found in 30.8 % of the catheters placed after skin disinfection with povidone-iodine , in 24.4 % after disinfection with propanol/chlorhexidine and in 4.7 % after disinfection with propanol/chlorhexidine followed by povidone-iodine ( p=0.006 ) . In 15 cases , the same organism was isolated from the skin swab and the catheter tip . Ten of these paired isolates showed the same pattern in a pulsed-field gel electrophoresis analysis . Conclusions Skin disinfection with propanol/chlorhexidine followed by PVP-iodine was superior in the prevention of microbial CVC colonisation compared to either of the regimens alone . These results support the concept that catheter infections can originate from bacterial translocation at the time of catheter insertion OBJECTIVE To determine the efficacy and tolerability of octenidine hydrochloride , a non-alcoholic skin antiseptic , for the care of central venous catheter ( CVC ) insertion sites . DESIGN Prospect i ve , observational study . SETTING Bone marrow transplantation unit of a university hospital . PATIENTS All consecutive patients with a nontunneled CVC were enrolled prospect ively after informed consent . METHODS Octenidine hydrochloride ( 0.1 % ) was applied for disinfection at the CVC insertion site during dressing changes . The following cultures were performed weekly as well as at the occurrence of any systemic inflammatory response syndrome criteria : cultures of the skin surrounding the CVC entry site , cultures of the three-way hub connected to the CVC , blood cultures , and cultures of the CVC tip on removal . Enhanced microbiological methods ( skin swabs of a 24-cm2 st and ardized area , roll plate , and sonication of catheter tips ) were applied . RESULTS One hundred thirty-five CVCs were inserted in 62 patients during the study period and remained for a mean period of 19.1 days , corresponding to 2,462 catheter-days . Bacterial density at the insertion site declined substantially over time , and most cultures became negative 2 weeks after insertion . Only 6 patients had a documented catheter-related bloodstream infection . The incidence density was 2.39 catheter infections per 1,000 catheter-days . No side effects were noted with application of the antiseptic . CONCLUSIONS Disinfection with a skin antiseptic that contains octenidine hydrochloride is highly active and well tolerated . It leads to a decrease in skin colonization over time and may be a new option for CVC care BACKGROUND A meta- analysis and cost-effectiveness analysis of r and omized controlled trials comparing chlorhexidine gluconate with povidone-iodine solutions for venous catheter site care found that the use of chlorhexidine gluconate significantly reduced the risk for catheter-related bloodstream infections and that it was cost-effective . The objective of the study was to implement locally formulated chlorhexidine gluconate for central venous catheter ( CVC ) site care in intensive care units ( ICUs ) at Siriraj Hospital . METHODS The study was conducted in 312 subjects who needed CVC insertions in 3 ICUs from January to July 2006 . One hundred twenty subjects received 2 % chlorhexidine gluconate in 70 % alcohol , whereas 192 subjects received 10 % povidone-iodine as the antiseptic solution for CVC site care . The patients were assessed for CVC-related infections and for any adverse effects of 2 % chlorhexidine gluconate in 70 % alcohol . RESULTS The incidence of CRBSIs in the indwelling CVC subjects who received 2 % chlorhexidine gluconate in 70 % alcohol was less than those who received 10 % povidone-iodine during the same period , 3.2 versus 5.6 episodes per 1000 CVC days , respectively ( P= .06 ; OR , 3.26 ; 95 % CI : 0.97 - 10.92 ) . No adverse effects related to using 2 % chlorhexidine gluconate in 70 % alcohol were observed . CONCLUSION The locally formulated 2 % chlorhexidine gluconate in 70 % alcohol was safe , effective , and efficient for CVC site care in ICUs at Siriraj Hospital Objective To compare effectiveness in preventing central venous catheter colonization and infection of two protocol s of cutaneous antisepsis using povidone-iodine solution in combination with ethanol or water . Design R and omized trial . Setting Medical intensive care department in a university hospital . Patients Consecutive patients requiring central venous catheter in two similar 11-bed units from January 1 , 2001 , to January 1 , 2002 . Interventions Alcoholic povidone-iodine solution protocol was r and omly assigned to one of two units when the study began . Every 3 months the alcoholic protocol was switched from one unit to the other . Depending on the unit and the time the patient was admitted , catheters were inserted and cared for with 10 % aqueous povidone-iodine solution or 5 % povidone-iodine solution 70 % ethanol-based combination . Measurements and Main Results Rates of catheter colonization , catheter-related bacteremia , and catheter-related infection were compared in the two protocol s ; 223 catheters were included in an intent-to-treat analysis . The incidence of catheter colonization was significantly lower in the alcoholic povidone-iodine solution protocol than in the aqueous povidone-iodine solution protocol ( relative risk , 0.38 ; 95 % confidence interval , 0.22–0.65 , p < .001 ) , and so was the incidence of catheter-related infection ( relative risk , 0.34 ; 95 % confidence interval , 0.13–0.91 , p < .04 ) . Catheter-related bacteremia were similar in both protocol s. After adjusting for other risk factors , time to central venous catheter colonization was significantly longer in the alcoholic solution ( adjusted hazards ratio , 0.3 ; 95 % confidence interval , 0.2–0.6 , p < .001 ) . Based on a subgroup of 114 patients ( 57 in each protocol ) , analysis of 57 pairs of central venous catheters matched for age , duration , and site of insertion found similar results regarding the superiority of alcoholic povidone-iodine solution in preventing central venous catheter colonization and infection . Conclusions The use of alcoholic povidone-iodine for skin disinfection reduced the incidence of catheter colonization and related infection compared with aqueous 10 % povidone-iodine disinfection in an adult intensive care unit To compare the efficacy of two commercially available , alcohol-based antiseptic solutions for preparation and care of central venous catheter ( CVC ) insertion sites , with and without octenidine dihydrochloride , a double-blind , r and omized , controlled trial was undertaken in the haematology units and in one surgical unit of two university hospitals . Adult patients with a non-tunnelled CVC were r and omly assigned to two different skin disinfection regimens at the insertion site : 0.1 % octenidine with 30 % 1-propanol and 45 % 2-propanol , and as control 74 % ethanol with 10 % 2-propanol . Endpoints were ( i ) skin colonization at the insertion site ; ( ii ) positive culture from the catheter tip ( > or = 15 CFU ) ; and ( iii ) occurrence of CVC-associated bloodstream infection ( defined according to criteria set by the CDC ) . Four hundred patients with inserted CVC were enrolled from May 2002 through April 2005 . Both groups were similar in respect of patient characteristics and co-morbidities . Skin colonization at the CVC insertion site during the first 10 days was significantly reduced by octenidine treatment ( relative difference octenidine vs. control : 0.21 ; 95%CI : 0.11 - 0.39 , p < 0.0001 ) . Positive culture of the catheter tip was significantly less frequent in the octenidine group ( 7.9 % ) than in the control group ( 17.8 % ) : OR = 0.39 ( 95%CI : 0.20 - 0.80 , p 0.009 ) . Patients treated with octenidine had a non-significant reduction in catheter-associated bloodstream infections ( 4.1 % vs. 8.3 % ; OR = 0.44 ; 95%CI : 0.18 - 1.08 , p 0.081 ) . Side effects were similar in both groups . This r and omized controlled trial supports the results of two observational studies demonstrating octenidine in alcoholic solution to be a better option than alcohol alone for the prevention of CVC-associated infections UNLABELLED Neonates who require a central venous catheter ( CVC ) for prolonged vascular access experience high rates of catheter-related bloodstream infection ( CRBSI ) . PURPOSE A multicenter r and omized clinical trial was undertaken to ascertain the efficacy of a novel chlorhexidine-impregnated dressing ( Biopatch Antimicrobial Dressing ) on the CVC sites of neonates for the prevention of catheter tip colonization , CRBSI , and bloodstream infection ( BSI ) without a source . Setting . Six level III neonatal intensive care units . Patients Studied . Neonates admitted to study units who would require a CVC for at least 48 hours . METHODS Eligible infants were r and omized before catheter placement to 1 of the 2 catheter site antisepsis regimens : 1 ) 10 % povidone-iodine ( PI ) skin scrub , or 2 ) a 70 % alcohol scrub followed by placement of a chlorhexidine-impregnated disk over the catheter insertion site . A transparent polyurethane dressing ( Bioclusive Transparent Dressing ) was used to cover the insertion site in both study groups . Primary study outcomes evaluated were catheter tip colonization , CRBSI , and BSI without an identified source . RESULTS Seven hundred five neonates were enrolled in the trial , 335 r and omized to receive the chlorhexidine dressing and 370 to skin disinfection with PI ( controls ) . Neonates r and omized to the antimicrobial dressing group were less likely to have colonized CVC tips than control neonates ( 15.0 % vs 24.0 % , relative risk [ RR ] : 0.6 95 % confidence interval [ CI ] : 0.5 - 0.9 ) . Rates of CRBSI ( 3.8 % vs 3.2 % , RR : 1.2 , CI : 0.5 - 2.7 ) and BSI without a source ( 15.2 % vs 14.3 % , RR : 1.1 , CI : 0.8 - 1.5 ) did not differ between the 2 groups . Localized contact dermatitis from the antimicrobial dressing , requiring crossover into the PI treatment group , occurred in 15 ( 15.3 % ) of 98 exposed neonates weighing < /=1000 g. No neonates in the PI group developed contact dermatitis . CONCLUSION The novel chlorhexidine-impregnated dressing , replaced weekly , was as effective as cutaneous disinfection with 10 % PI and redressing the site every 3 to 7 days for preventing CRBSI and BSI without a source in critically ill neonates requiring prolonged central venous access . The risk of local contact dermatitis under the chlorhexidine dressing limits its use in low birth weight infants who require prolonged central access during the first 2 weeks of life Povidone-iodine ointment and gauze covered by transparent dressings were compared with transparent dressings alone in historical controls ( both changed twice weekly ) in neurosurgical patients needing catheter placement for prolonged periods . Colonization and bloodstream infection were both reduced with the new method ( P < .01 and P = .062 , respectively ) More than 90 % of all intravascular device-related septicaemias are due to central venous or arterial catheters . To assess the efficacy of cutaneous antisepsis to prevent catheter-associated infection , we prospect ively studied three antiseptics for disinfection of patients ' central venous and arterial catheter insertion sites in a surgical intensive care unit . 668 catheters were r and omised to 10 % povidone-iodine , 70 % alcohol , or 2 % aqueous chlorhexidine disinfection of the site before insertion and for site care every other day thereafter . Chlorhexidine was associated with the lowest incidence of local catheter-related infection ( 2.3 per 100 catheters vs 7.1 and 9.3 for alcohol and povidone-iodine , respectively , p = 0.02 ) and catheter-related bacteraemia ( 0.5 vs 2.3 and 2.6 ) . Of the 14 infusion-related bacteraemias ( 4 due to contaminated infusate or catheter hub , 10 due to infected catheters ) , 1 was in the chlorhexidine group and 13 were in the other two groups ( odds ratio 0.16 , p = 0.04 ) . We conclude that use of 2 % chlorhexidine , rather than 10 % povidone-iodine or 70 % alcohol , for cutaneous disinfection before insertion of an intravascular device and for post-insertion site care can substantially reduce the incidence of device-related infection Objective Analysis of infectious complications and risk factors in percutaneous central venous catheters . Design One-year observational , prospect i ve , multicenter study ( 1998–1999 ) . Setting Twenty Spanish pediatric intensive care units . Patients Eight hundred thirty-two children aged 0–14 years . InterventionNone . Measurements and main results One thous and ninety-two catheters were analyzed . Seventy-four ( 6.81 % ) catheter-related bloodstream infections ( CRBSI ) were found . The CRBSI rate was 6.4 per 1,000 CVC days ( 95 % CI 5.0–8.0 ) . Risk factors for CRBSI were weight under 8 kg ( p < 0.001 ) , cardiac failure ( RR 2.69 ; 95 % CI 1.95–4.38 ; p < 0.001 ) , cancer ( RR 1.66 ; 95 % CI 0.97–2.78 ; p = 0.05 ) , silicone catheters ( RR 2.82 ; 95 % CI 1.49–5.35 ; p = 0.006 ) , guidewire exchange catheterization ( p = 0.002 ) , obstructed catheters ( RR 2.67 ; 95 % CI 1.63–4.39 ; p < 0.001 ) , and more than 12 days ' indwelling time ( RR 5.9 ; 95 % CI 3.63–9.41 ; p < 0.001 ) . Multivariate Cox regression identified lower patient weight ( HR 2.4 ; 95 % CI 1.11–5.19 ; p = 0.002 ) , guidewire exchange catheterization ( HR 2.2 ; 95 % CI 1.07–4.54 ; p = 0.049 ) and more than 12 days ' indwelling time ( HR 1.97 ; 95 % CI 0.89–4.36 ; p = 0.089 ) as significant independent predictors of CRBSI . Factors which protected against infection were the use of povidone – iodine on hubs ( HR 0.42 ; 95 % CI 0.19–0.96 ; p = 0.025 ) and porous versus impermeable dressing ( HR 0.41 ; 95 % CI 0.23–0.74 ; p = 0.004 ) . Two children ( 0.24 % ) died from endocarditis following catheter-related sepsis due to Stenotrophomonas maltophilia in one case and P. aeruginosa in the other . Conclusions Catheter-related sepsis is associated with lower patient weight and more than 12 days ' indwelling time , but not with the insertion site . Cleaning hubs with povidone – iodine protects from infection BACKGROUND Chlorhexidine bathing has been associated with reductions in healthcare-associated bloodstream infection . To determine the impact and sustainability of the effect of chlorhexidine bathing on central venous catheter-associated bloodstream infection , we performed a prospect i ve , 3-phase , multiple-hospital study . METHODS In the medical intensive care unit and the respiratory care unit of a tertiary care hospital and the medical-surgical intensive care units of 4 community hospitals , rates of central venous catheter-associated bloodstream infection were collected prospect ively for each period . Pre-intervention ( phase 1 ) patients were bathed with soap and water or nonmedicated bathing cloths ; active intervention ( phase 2 ) patients were bathed with 2 % chlorhexidine gluconate cloths with the number of baths administered and skin tolerability assessed ; post-intervention ( phase 3 ) chlorhexidine bathing was continued but without oversight by research personnel . Central venous catheter-associated bloodstream infection rates were compared over study periods using Poisson regression . RESULTS Compared with pre-intervention , during active intervention there were significantly fewer central venous catheter-associated bloodstream infections ( 6.4/1000 central venous catheter days vs 2.6/1000 central venous catheter days , relative risk , 0.42 ; 95 % confidence interval , 0.25 - 0.68 ; P<.001 ) , and this reduction was sustained during post-intervention ( 2.9/1000 central venous catheter days ; relative risk , 0.46 ; 95 % confidence interval , 0.30 - 0.70 ; P<.001 ) . During the active intervention period , compliance with chlorhexidine bathing was 82 % . Few adverse events were observed . CONCLUSION In this multiple-hospital study , chlorhexidine bathing was associated with significant reductions in central venous catheter-associated bloodstream infection , and these reductions were sustained post-intervention when chlorhexidine bathing was unmonitored . Chlorhexidine bathing was well tolerated and is a useful adjunct to reduce central venous catheter-associated bloodstream infection Objective : Determine the impact of three stepwise interventions on the rate of central catheter-associated bloodstream infections . Design : Quasi-experimental study . Setting : Three surgical intensive care units ( general surgery , trauma , and neurosurgery ) at a 1500-bed county teaching hospital in the Miami metro area . Patients : All consecutive central catheter-associated bloodstream infection cases as determined by the Infection Control Department . Interventions : Three interventions aim ed at catheter maintenance were implemented at different times in the units : chlorhexidine “ scrub-the-hub , ” chlorhexidine daily baths , and daily nursing rounds aim ed at assuring compliance with an intensive care unit goal -oriented checklist . Measurements and Main Results : The primary outcome was the monthly intensive care unit rate of central catheter-associated bloodstream infections ( infections per 1000 central catheter days ) . Over 33 months of follow-up ( July 2008 to March 2011 ) , we found decreased rates in each of the three intensive care units evaluated during the interventions , especially after implementation of chlorhexidine daily baths . Rates in unit A decreased from a rate of 8.6 to 0.5 , unit B from 6.9 to 1.6 , and unit C from 7.8 to 0.6 . Secondary bloodstream infection rates remained unchanged throughout the observation period in units A and B ; however , unit C had a decrease in its rates over time . Conclusions : We report the progressive reduction of central catheter-associated bloodstream infection rates after the stepwise implementation of chlorhexidine “ scrub-the-hub ” and daily baths in surgical intensive care units , suggesting effectiveness of these interventions Central venous lines are now common in children who need a permanent form of intravenous access . These lines frequently become infected . This study compared the effects of different antiseptics ( Hibiclens [ chlorhexadine 4 % ; Stuart Pharmaceutical , Wilmington , DE ] and Betadine [ povidone-iodine , Clini Pad Corp , Guilford , CT ] ) used to clean the skin as well as the dressings used to cover the exit site ( Tegaderm [ 3-M Medical-Surgical Division , St Paul , MN ] and gauze ) on microorganism growth on the skin in a pediatric oncology population . Sixty subjects were recruited from the oncology and bone marrow transplant units of Children 's Hospital in Boston , MA . The subjects were r and omly assigned to one of four dressing groups . These included : 1 , Betadine and Tegaderm ; 2 , Betadine and gauze ; 3 , Hibiclens and Tegaderm ; and 4 , Hibiclens and gauze . Dressings were done on a Monday-Wednesday-Friday basis . Quantitative cultures were obtained before the first and after the fifth dressing changes . There were no significant differences in incidence of bacterial growth between dressing groups ( F = 1.05 , P = .377 ) . Redness ( F = 3.01 , P = .037 ) and swelling ( F = 2.75 , P = .051 ) were more frequently seen in Betadine groups . Boys were more often infected than girls . ( χ 2 = 4.075 , P = .044 The use of chlorhexidine gluconate solution for vascular catheter insertion site care reduces the risk of catheter-related bloodstream infection by one-half , compared with povidone iodine . Our objective was to evaluate the cost-effectiveness of chlorhexidine gluconate versus povidone iodine . We used data from r and omized , controlled trials , meta-analyses , and epidemiologic studies to construct a decision analysis model . We estimated that use of chlorhexidine , rather than povidone , for central catheter site care result ed in a 1.6 % decrease in the incidence of catheter-related bloodstream infection , a 0.23 % decrease in the incidence of death , and savings of 113 dollars per catheter used . For peripheral catheter site care , the results were similar , although the differences were smaller . The results were found to be robust on multivariate sensitivity analyses . Use of chlorhexidine gluconate in place of the current st and ard solution for vascular catheter site care is a simple and cost-effective method of improving patient safety in the hospital setting In an attempt to decrease the incidence of central venous catheter sepsis in children with cancer , we conducted a study to evaluate the benefit of adding broad-spectrum antibiotics to the catheter " flush solution . " In a prospect i ve , placebo-controlled , double-blinded , r and omized trial , 69 children with different types of malignancies were studied . The central venous catheters in these children were flushed with either the st and ard solution ( normal saline + 100 U/ml of heparin ) or the study solution ( 25 microgram/ml of both amikacin and vancomycin added to the st and ard solution ) . At the conclusion of the study , 64 children with a total of 67 indwelling central venous lines were assessable . The total catheter days on study were 20,700 days , with a median of 323 catheter days per patient . We documented 10 events of catheter-related infections ( 0.49 events/1,000 catheter days at risk ) . Five of these events were catheter-related sepsis ( 0.24 sepses/1,000 catheter days ) : two were fungal and three were bacterial . Due to the low incidence of catheter-related sepsis in this study , no statement regarding the prophylactic use of antibiotics could be made . The extremely low rate of catheter-related sepsis reported herein may be retrospectively attributed to continuous staff education regarding aseptic techniques in h and ling these catheters . Staff education is essential , and probably the most effective factor in preventing catheter-related sepsis Abstract Central venous catheterization is one of the important sepsis reasons in surgical patients . In this r and omized controlled study , the effect of the frequency and type of catheter site care , as well as age , coexisting malignancy or diabetes mellitus , total parenteral nutrition administration and antibiotics use , on central venous catheter infection was investigated . Seventy-two single-lumen polyurethane catheters were included . In group I ( n : 33 ) , a transparent occlusive dressing was applied to the insertion site and not removed for 7 days unless there were signs of local infection . In group II ( n : 39 ) , daily site care was done with povidone-iodine 10 % solution and a new sterile gauze was applied . Chi-square , linear correlation and multiple regression tests were used for statistical analysis . Mean duration of catheters was 8 ±4 days . There was no catheter-related sepsis . Ten ( 13.9 % ) patients had positive catheter tip cultures of whom three had site infection as well . The incidence of site and tip infections were not significantly different in group I and II ( p > 0.05 ) . Site infection and age younger than 60 years significantly increased the rate of tip infection ( p : 0.004 and p : 0.02 respectively ) . Total parenteral nutrition administration was associated with higher rate of tip infection ( p : 0.06 ) . Coexisting malignancy or diabetes mellitus , duration of catheter and antibiotics use did not have any significant effect on the rate of central venous catheter infections ( p > 0.05 ) . In conclusion , we observed that the frequency of insertion site care and the type of dressing applied to the site had no significant effect on the rate of CVC infection . Insertion site infection was the most significant factor increasing the incidence of catheter tip infection . The use of the CVC for total parenteral nutrition facilitated tip infection as well The microbial contamination rate of luers of central venous catheters ( CVCs ) with either PosiFlow needleless connectors or st and ard caps attached was investigated . The efficacy of 70 % ( v/v ) isopropyl alcohol , 0.5 % ( w/v ) chlorhexidine in gluconate 70 % ( v/v ) isopropyl alcohol and 10 % ( w/v ) aqueous povidone-iodine to disinfect the intravenous connections was also assessed . Seventy-seven patients undergoing cardiac surgery who required a CVC as part of their clinical management were r and omly allocated either needleless connectors or st and ard caps . Patients were also design ated to receive chlorhexidine/alcohol , isopropyl alcohol or povidone-iodine for pre-CVC insertion skin preparation and disinfection of the connections . After 72 h in situ the microbial contamination rate of 580 luers , 306 with st and ard caps and 274 with needleless connectors attached , was determined . The microbial contamination rate of the external compression seals of 274 needleless connectors was also assessed to compare the efficacy of the three disinfectants . The internal surfaces of 55 out of 306 ( 18 % ) luers with st and ard caps were contaminated with micro-organisms , whilst only 18 out of 274 ( 6.6 % ) luers with needleless connectors were contaminated ( P<0.0001 ) . Of those needleless connectors disinfected with isopropyl alcohol , 69.2 % were externally contaminated with micro-organisms compared with 30.8 % disinfected with chlorhexidine/alcohol ( P<0.0001 ) and 41.6 % with povidone-iodine ( P<0.0001 ) . These results suggest that the use of needleless connectors may reduce the microbial contamination rate of CVC luers compared with the st and ard cap . Furthermore , disinfection of needleless connectors with either chlorhexidine/alcohol or povidone-iodine significantly reduced external microbial contamination . Both these strategies may reduce the risk of catheter-related infections acquired via the intraluminal route Objective : The purpose of this pilot trial was to determine whether rates of contact dermatitis following cutaneous antisepsis for central catheter placement were similar among neonates treated with chlorhexidine gluconate and povidone-iodine . Chlorhexidine gluconate absorption was also evaluated . Study Design : Infants weighing ⩾1500 g and ⩾7 days of age were r and omized to a 10 % povidone-iodine or 2 % chlorhexidine gluconate site scrub before catheter placement . Primary outcomes evaluated included dermatitis , catheter colonization and chlorhexidine gluconate absorption . Result : A total of 48 neonates were enrolled . Colonization rates were similar among treatment groups ( P<0.6 ) . Dermatitis did not occur at chlorhexidine gluconate ( central catheters , n=24 ; peripheral catheters , n=29 ) sites . Seven neonates had measurable chlorhexidine gluconate concentrations ( range 13 to 100 ng ml−1 ) during catheterization . Conclusion : In this small trial chlorhexidine gluconate antisepsis was tolerated by study neonates . Chlorhexidine gluconate was cutaneously absorbed . Larger trials are needed to determine efficacy and tolerance of chlorhexidine gluconate in neonates The cluster r and omized trial with a concurrent economic evaluation is considered the gold st and ard evaluative design for the conduct of implementation research evaluating different strategies to promote the transfer of research findings into clinical practice . This has implication s for the planning of such studies , as information is needed on the effects of clustering on both effectiveness and efficiency outcomes . This paper describes the design considerations specific to implementation research studies , focusing particularly on the estimation of sample size requirements and on the need for reliable information on intracluster correlation coefficients for both effectiveness and efficiency outcomes A multicenter prospect i ve , r and omized , controlled trial , with 0.5 % tincture of chlorhexidene versus 10 % povidone-iodine as cutaneous antisepsis for central venous catheter ( CVC ) insertion , was conducted for patients in intensive care units . Of 374 patients , 242 had a CVC inserted for > 3 days and were used for the primary analysis . Outcomes included catheter-related bacteremia , significant catheter colonization ( > or = 15 colony-forming units [ cfu ] ) , exit-site infection , serial quantitative exit-site culture ( every 72 h ) , and molecular subtyping of all isolates . Patients in both study groups were comparable with respect to age , sex , underlying disease , length of hospitalization , reason for line insertion , and baseline APACHE II score . Documented catheter-related bacteremia rates were 4.6 cases per 1000 catheter-days in the chlorhexidine group ( n=125 ) and 4.1 cases per 1000 catheter-days in the povidone-iodine group ( n=117 ; not significant [ NS ] ) . Significant catheter-tip colonization occurred in 24 ( 27 % ) of 88 patients in the povidone-iodine group and in 31 ( 34 % ) of 92 patients in the chlorhexidine group ( NS ) . A mean exit-site colony count of 5.9 x 10(5 ) cfu/mL per 25 cm(2 ) of the surface area of skin in the povidone-iodine group versus 3.1 x 10(5 ) cfu/mL per 25 cm(2 ) in the chlorhexidine group ( NS ) was found . There was a trend toward fewer exit-site infections in the chlorhexidine group ( 0 of 125 patients ) versus those in the povidone-iodine group ( 4 of 117 patients ; P=.053 ) . Results of an intention-to-treat analysis were unchanged from the primary analysis . No difference was demonstrable between 0.5 % tincture of chlorhexidine and 10 % povidone-iodine when used for cutaneous antisepsis for CVC insertion in patients in the intensive care unit BACKGROUND In 2003 , through the Greater Cincinnati Health Council nine health care systems agreed to participate and fund 50 % of a two-year project to reduce hospital-acquired infections among patients in intensive care units ( ICU ) and following surgery ( SIP ) . METHODS Hospitals were r and omized to either the CR-BSI or SIP project in the first year , adding the alternative project in year 2 . Project leaders , often the infection control professionals , implemented evidence -based practice s to reduce catheter-related blood stream infections ( CR-BSIs ; maximal sterile barriers , chlorhexidine ) at their hospitals using a collaborative approach . Team leaders entered process information in a secure deidentifled Web-based data base . RESULTS Of the four initial sites r and omized to CR-BSI reduction , all reduced central line infections by 50 % ( CR-BSI , 1.7 to 0.4/1000 line days , p < .05 ) . At the project midpoint ( 3 quarters of 2004 ) , adherence to evidence -based practice s increased from 30 % to nearly 95 % . DISCUSSION The direct role of hospital leadership and development of a local community of practice , facilitated cooperation of physicians , problem solving , and success . Use of forcing functions ( removal of betadine in kits , creation of an accessory pack and a checklist for line insertion ) improved reliability . The appropriate floor for central line infections in ICUs is < 1 infection /1,000 line days This study examined a simple technique for reducing contamination during catheterization of the internal jugular vein . Sixty patients were assigned r and omly to receive either a traditional iodophor skin cleansing or an alcohol cleansing , followed by application of an iodophor-impregnated sterile film . In the cleansed with iodophor alone group , 83 % of the anesthesiologists ' glove tips were contaminated , and 13 % of the catheter tips were contaminated . In contrast , in the group in which the sterile film was employed , contamination of gloves and catheters was virtually eliminated Context : Infectious complications of invasive procedures affect patient outcomes adversely . Choice of antiseptic solution at the time of insertion is one of the major factors affecting their incidence . Aims : This study was undertaken to compare efficacy of chlorhexidine 2 % and povidone iodine 10 % for skin disinfection prior to placement of epidural and central venous catheters ( CVCs ) . Setting s and Design : A prospect i ve r and omised trial in the operating rooms of a tertiary referral cancer centre . Methods : Sixty consecutive adult patients undergoing elective oncosurgery requiring placement of epidural and CVCs were enrolled . Paired skin swabs were collected before and after application of the antiseptic solution . The sample s were incubated in McConkey 's media and blood agar at 35 ° C for up to 24 h. Any bacterial growth was grade d as : < 10 colonies - poor growth , 10 - 50 colonies - moderate growth and > 50 colonies as heavy growth . Data on demographics and antibiotic prophylaxis and costs was collected for all patients . Statistical Analysis : Student 's t-test and Mann-Whitney tests were used to analyse data , P<0.05 was considered significant . Results : Demographics and antibiotic prophylaxis use was similar in both groups . Before application of antiseptic solution , a variety of micro-organisms were grown from most patients with growth ranging from none-heavy . No organism was grown after application of either antiseptic solution from any patient . Conclusions : We found no differences between 2 % chlorhexidine and 10 % povidone-iodine for skin disinfection in regard to costs , efficacy or side-effects OBJECTIVES To compare the efficacy of a newly available antiseptic solution ( composed of 0.25 % chlorhexidine gluconate , 0.025 % benzalkonium chloride , and 4 % benzyl alcohol ) , with 10 % povidone iodine , on the prevention of central venous or arterial catheter colonization and infection . DESIGN Prospect i ve , r and omized clinical trial . SETTING Surgical-trauma intensive care unit ( ICU ) in a university hospital . PATIENTS All patients admitted to the ICU and requiring the insertion of a central venous and /or an arterial catheter from July 1 , 1992 to October 31 , 1993 . INTERVENTIONS Patients were r and omly assigned to one of two groups according to the antiseptic solution used for insertion and catheter care . The same solution was used for skin disinfection from the time of catheter insertion to the time of removal of each catheter . MEASUREMENTS AND MAIN RESULTS Catheter distal tips were quantitatively cultured when catheters were no longer necessary , if there was a suspicion of catheter-related infection , and routinely after 7 days of use for arterial catheters , or after 15 days of use for central venous catheters . The rate of significant catheter colonization ( i.e. , > or = 10(3 ) colony-forming units [cfu]/mL by quantitative culture ) , and catheter-related sepsis ( as defined by sepsis abating following catheter removal per 1,000 catheter-days ) , were significantly lower in the chlorhexidine group ( 12 vs. 31 [ relative risk 0.4 , 95 % confidence interval 0.1 to 0.9 , p < .01 ] and 6 vs. 16 [ relative risk 0.4 , 95 % confidence interval 0.1 to 1 , p = 0.5 ] , respectively ) . The rate of central venous catheter colonization and central venous catheter-related sepsis per 1,000 catheter-days were also significantly lower in the chlorhexidine group ( 8 vs. 31 [ relative risk 0.3 , 95 % confidence interval 0.1 to 1 , p = .03 ] and 5 vs. 19 [ relative risk 0.3 , 95 % confidence interval 0.1 to 1 , p = .02 ] , respectively ) . Finally , the rate of arterial catheter colonization per 1,000 catheter-days was significantly lower in the chlorhexidine group ( 15 vs. 32 [ relative risk 0.5 , 95 % confidence interval 0.1 to 1 , p = .05 ] ) , whereas the rate of arterial catheter-related sepsis per 1,000 catheter-days was similar for the two study groups ( 8 in the chlorhexidine group vs. 10 in the povidone iodine group [ relative risk 0.8 , 95 % confidence interval 0.1 to 2.2 , p = .6 ] ) . The 0.25 % chlorhexidine solution was superior to the 10 % povidone iodine solution in preventing catheter colonizations and catheter-related sepsis due to Gram-positive bacteria ( 5 vs. 20 [ p < .001 ] , and 2 vs. 10 [ p < .001 ] , respectively ) , whereas the activity of the 0.25 % chlorhexidine solution was nonsignificantly superior in preventing Gram-negative infections ( 7 vs. 4 [ p = .5 ] , and 4 vs. 2 [ p = .8 ] , respectively ) . CONCLUSIONS The 4 % alcohol-based solution of 0.25 % chlorhexidine gluconate and 0.025 % benzalkonium chloride was more effective than 10 % povidone iodine for insertion site care of short-term central venous and arterial catheters . This effect appeared related to a more efficacious prevention of infections with Gram-positive bacteria Fifty burn patients who had central venous cannulations performed were r and omly assigned to one of two groups . In group 1 , the skin around the catheter insertion site was cleaned with 70 % isopropyl alcohol prior to catheter removal . In group 2 , the skin around the catheter insertion site was not cleaned prior to catheter removal . Twenty ( 40 % ) of the patients had negative cultures . The remaining 30 patients had positive cultures , 11 ( 37 % ) of which were positive for both skin and catheter tip specimens . All 11 of these cultures matched for the same organism . Six ( 55 % ) were from group 1 and five ( 45 % ) from group 2 . Of the 14 patients with cultures positive for the catheter tips but not the skin , eight ( 57 % ) did not have the skin cleaned prior to catheter removal . Five skin cultures were positive , with no organism growth on the corresponding catheter tip ; four ( 80 % ) of these were from group 2 . Data from blood and intravenous ( IV ) catheter tip cultures performed from November 1982 through December 1985 demonstrated that of the 441 blood cultures obtained , 91 ( 21 % ) were positive . Twenty-seven ( 6 % ) were positive blood and IV catheter tip cultures ; only ten ( 37 % ) of these matched for the same organism , accounting for only 2 % of the total number of cultures obtained The purpose of this trial was to prepare for a large r and omized trial comparing Arglaes film dressing , a recent innovation containing silver ions , against Tegaderm , a transparent polyurethane dressing . Thirty-one patients admitted to the intensive care unit and requiring the insertion of an arterial line or central venous catheter were recruited into the study . Skin swabs were taken from the insertion sites prior to catheterization and on removal of the intravascular device to measure skin colonization rate between the two dressings . The catheter tips were also cultured on removal to establish if there was a difference between the two groups . No statistical differences were found in bacterial growth between the two dressings Background : The Centers for Disease Control and Prevention guideline recommended the use of 2 % chlorhexidine as a percutaneous disinfectant for central venous catheter ( CVC ) insertion . However , in Japan , 0.05 % chlorhexidine is commonly used as well as 10 % povidone-iodine , instead of 2 % chlorhexidine . Purpose : It was the aim of this study to examine whether the use of 0.05 % chlorhexidine is inferior to conventional 10 % povidone-iodine as a percutaneous disinfectant for preventing CVC-related bloodstream infection ( CVC-RBSI ) . Methods : Between September 2006 and July 2008 , the time interval from insertion to development of CVC-RBSI was compared prospect ively between patients prepared with 0.05 % chlorhexidine ( group 1 , n = 286 CVCs ) and those prepared with conventional 10 % povidone-iodine ( group 2 , n = 298 CVCs ) . Results : Two hundred and thirty-nine patients received 584 CVCs for a total of 6,205 catheter-days . CVC-RBSI ( 3.22 per 1,000 catheter-days ) was diagnosed in 20 cases . There were no significant differences in patient background factors between group 1 and 2 , except for blood culture positivity ( p = 0.0450 ) . However , Kaplan-Meier analysis and the log rank test revealed no significant difference between group 1 and 2 in the time interval from insertion until development of CVC-RBSI . Conclusions : Use of 0.05 % chlorhexidine is not inferior to conventional 10 % povidone-iodine as a cutaneous disinfectant for the prevention of CVC-RBSI We studied etiologic factors important in colonization of 179 central venous catheters ( CVCs ) in patients r and omized into group 1 ( who received daily topical applications of povidoneiodine ) or group 2 ( who received only dry dressing changes ) . Colonization rates of CVC tips were similar between group 1 ( 18/84 or 21 % ) and group 2 ( 22/95 or 23 % ) . Peripheral blood cultures grew C and ida in eight hyperalimented patients ( evenly divided between groups 1 and 2 ) , S epidermidis in four other patients ( also evenly divided ) , and gram-negative bacteria in three patients . Colonization rates for CVCs in place for 0 to seven days was 15.6 % ( 17/109 ) and 76.7 % ( 23/30 ) if used from eight to 30 days . Inflammatory signs at CVC sites were often absent when CVCs became colonized or produced bacteremia . Unimportant determinants of CVC colonization included skin securement of CVCs , antibiotic infusions through CVC lines , and masking and gowning of physicians before CVC placement . Daily applications of povidone-iodine did not reduce colonization of CVCs as compared to dry dressing changes Background : Protection of the catheter site by antimicrobial agents is one of the most important factors in the prevention of infection . Povidone iodine and chlorhexidine gluconate are the most common used agents for dressing . The purpose of this study was to compare the effects of povidone iodine , chlorhexidine gluconate and octenidine hydrochloride in preventing catheter related infections . Material s and Methods : Patients were r and omized to receive ; 4 % chlorhexidine gluconate , 10 % povidone iodine or octenidine hydrochlorodine for cutaneous antisepsis . Cultures were taken at the site surrounding catheter insertion and at the catheter hub after removal to help identify the source of microorganisms . Results : Catheter related sepsis was 10.5 % in the povidone iodine and octenidine hydrochlorodine groups . Catheter related colonization was 26.3 % in povidone iodine group and 21.5 % in octenidine hydrochlorodine group . Conclusion : 4 % chlorhexidine or octenidine hydrochlorodine for cutaneous disinfection before insertion of an intravascular device and for post‑insertion site care can reduce the catheter related colonization |
13,854 | 31,307,510 | ConclusionS tudies have shown that PROMs can identify otherwise undetected symptoms .
Using PROMs proactively during the consultation has been shown to improve symptom management for patients with some other types of cancer . | Introduction The use of patient reported outcome measures ( PROMs ) has increased during the past decade , and the focus on how to use them has result ed in a more proactive application .
Studies have shown that proactive use of PROMs during treatment improves patient-clinician communication , leads to better symptom management and may prolong survival among advanced cancer patients .
Ovarian cancer is a serious disease in which the majority of patients experience recurrence during the follow-up period and suffer from a number of severe symptoms from underlying disease .
This systematic review was conducted to assess the evidence on the proactive use of PROMs as a dialogue tool during follow-up of ovarian cancer patients . | A structured question naire consisting of two parts was used to evaluate the impact of ovarian cancer and its management on quality of life in 28 patients with advanced disease . The first part rated their perceptions of behavioral disruption and emotional distress in five life areas , i.e. , activity , daily living , health , support , and outlook as set out by the interviewer-rated Spitzer question naire " Quality of Life Index of Cancer Patients . " The second part rated their response in the domain of sexual activity . Data were collected prospect ively at three monthly intervals during the 2-year descriptive study . In 12 patients ovarian cancer persisted despite surgery and chemotherapy result ing in the demise of 8 women within 2 years . During the first year of study these patients described a similar deterioration in quality of life as those who had a complete response to treatment . However , after 1 year , patients with persistent disease rated their quality of life much lower . Diagnosis of persistent disease after conventional treatment proved more stressful than the diagnosis of the primary disease . Treatment of ovarian cancer will produce behavioral disruption and emotional distress , with lasting affects seen even in patients with complete response 2 years after commencing therapy Background Women with platinum-resistant ovarian cancer are a heterogeneous group whose median overall survival is 12 months . We hypothesized that their quality of life ( QoL ) scores would be prognostic . Patients and methods Data from AURELIA ( n = 326 ) , a r and omized trial of chemotherapy with or without bevacizumab , were used to identify baseline QoL domains [ EORTC ( European Organisation for Research and Treatment of Cancer ) QLQ-C30 and OV28 ] that were significantly associated with overall survival in multivariable Cox regression analyses . Patients were classified as having good , medium , or poor risk . Cutpoints were vali date d in an independent data set , CARTAXHY ( n = 136 ) . Multivariable analyses of significant QoL domains on survival were adjusted for clinicopathological prognostic factors . The additional QoL information was assessed using C statistic . Results In AURELIA , all domains , except cognitive function , predicted overall survival in univariable analyses . Physical function ( P < 0.001 ) and abdominal/gastrointestinal symptom ( P < 0.001 ) scores remained significant in multivariable models . In high ( score < 67 ) , medium ( 67 - 93 ) , and low ( > 93 ) risk categories for physical function , median overall survival was 11.0 , 14.7 , and 19.3 months , respectively ( P < 0.001 ) . In CARTAXHY , median overall survival was 7.9 , 16.2 , and 23.9 months ( P < 0.001 ) , respectively . For high- ( > 44 ) , medium- ( 13 - 44 ) , and low- ( < 13 ) risk categories for abdominal/gastrointestinal symptoms , median overall survival was 11.9 , 14.3 , and 19.7 months in AURELIA ( P < 0.001 ) and 10.5 , 19.6 , and 24.1 months in CARTAXHY ( P = 0.02 ) . Physical function ( P = 0.02 ) and abdominal/gastrointestinal symptoms ( P = 0.03 ) remained independent prognostic factors after adjustment for clinicopathological factors . The C statistic of the full model was 0.71 . For QoL factors alone , patient factors alone and disease factors alone , the C statistics were 0.61 , 0.61 , and 0.67 respectively . Conclusions Physical function and abdominal/gastrointestinal symptom scores improved predictions of overall survival over clinicopathological factors alone in platinum-resistant ovarian cancer . This additional prognostic information could improve trial stratification , patient-doctor communication about prognosis , and clinical decision-making . Clinical trial registration NCT00976911 PURPOSE Although patient-reported cancer symptoms and quality -of-life issues ( SQLIs ) have been promoted as essential to a comprehensive assessment , efficient and efficacious methods have not been widely tested in clinical setting s. The purpose of this trial was to determine the effect of the Electronic Self-Report Assessment -Cancer ( ESRA-C ) on the likelihood of SQLIs discussed between clinicians and patients with cancer in ambulatory clinic visits . Secondary objectives included comparison of visit duration between groups and usefulness of the ESRA-C as reported by clinicians . PATIENTS AND METHODS This r and omized controlled trial was conducted in 660 patients with various cancer diagnoses and stages at two institutions of a comprehensive cancer center . Patient-reported SQLIs were automatically displayed on a graphical summary and provided to the clinical team before an on-treatment visit ( n = 327 ) ; in the control group , no summary was provided ( n = 333 ) . SQLIs were scored for level of severity or distress . One on-treatment clinic visit was audio recorded for each participant and then scored for discussion of each SQLI . We hypothesized that problematic SQLIs would be discussed more often when the intervention was delivered to the clinicians . RESULTS The likelihood of SQLIs being discussed differed by r and omized group and depended on whether an SQLI was first reported as problematic ( P = .032 ) . Clinic visits were similar with regard to duration between groups , and clinicians reported the summary as useful . CONCLUSION The ESRA-C is the first electronic self-report application to increase discussion of SQLIs in a US r and omized clinical trial Main purpose The objective of this study was to determine the relationship between clinician- grade d symptoms based on the common toxicity criteria ( CTC ) and patient-reported quality of life ( QoL ) . We hypothesized that toxicity symptoms that are objective or observable would have a higher correlation with QoL than subjective data . Material and methods A retrospective analyses of data from three closed r and omized chemotherapy trials was performed . A total of 2,110 patients with ovarian cancer ( stage IIB – IV ) who had complete toxicity and QoL data at cycles 3 and 6 were included . Toxicities were grade d according to the National Cancer Institute Common Toxicity Criteria . Quality of life was assessed every other cycle by using the European Organization for Research and Treatment of Cancer Quality of Life Question naire ( EORTC QLQ-C30).Main results Correlations between CTC grading and the QLQ-C30 functioning scales were weak ( < 0.30 ) ; correlation coefficients between CTC ratings and the QLQ-C30 symptom scales including nausea , vomiting , constipation , pain , and dyspnea ranged from 0.32 to 0.49 except for constipation ( 0.55 ) . On a symptom level exact agreement between clinician and patient reporting ranged from 54.2 % ( pain ) to 80.8 % ( emesis/vomiting ) . When symptom grading differed , patients reported greater severity for pain , constipation , and dyspnea , whereas clinicians grade d emesis/vomiting and nausea as more severe than the grading by patients . Conclusion Patient experience is not routinely captured by CTC toxicity scales . Therefore , clinicians should not entirely rely on the CTC grading but consider patient-reported outcomes as well PURPOSE There is growing interest to enhance symptom monitoring during routine cancer care using patient-reported outcomes , but evidence of impact on clinical outcomes is limited . METHODS We r and omly assigned patients receiving routine outpatient chemotherapy for advanced solid tumors at Memorial Sloan Kettering Cancer Center to report 12 common symptoms via tablet computers or to receive usual care consisting of symptom monitoring at the discretion of clinicians . Those with home computers received weekly e-mail prompts to report between visits . Treating physicians received symptom printouts at visits , and nurses received e-mail alerts when participants reported severe or worsening symptoms . The primary outcome was change in health-related quality of life ( HRQL ) at 6 months compared with baseline , measured by the EuroQol EQ-5D Index . Secondary endpoints included emergency room ( ER ) visits , hospitalizations , and survival . RESULTS Among 766 patients allocated , HRQL improved among more participants in the intervention group than usual care ( 34 % v 18 % ) and worsened among fewer ( 38 % v 53 % ; P < .001 ) . Overall , mean HRQL declined by less in the intervention group than usual care ( 1.4- v 7.1-point drop ; P < .001 ) . Patients receiving intervention were less frequently admitted to the ER ( 34 % v 41 % ; P = .02 ) or hospitalized ( 45 % v 49 % ; P = .08 ) and remained on chemotherapy longer ( mean , 8.2 v 6.3 months ; P = .002 ) . Although 75 % of the intervention group was alive at 1 year , 69 % with usual care survived the year ( P = .05 ) , with differences also seen in quality -adjusted survival ( mean of 8.7 v. 8.0 months ; P = .004 ) . Benefits were greater for participants lacking prior computer experience . Most patients receiving intervention ( 63 % ) reported severe symptoms during the study . Nurses frequently initiated clinical actions in response to e-mail alerts . CONCLUSION Clinical benefits were associated with symptom self-reporting during cancer care BACKGROUND Serum CA125 concentration often rises several months before clinical or symptomatic relapse in women with ovarian cancer . In the MRC OV05/EORTC 55955 collaborative trial , we aim ed to establish the benefits of early treatment on the basis of increased CA125 concentrations compared with delayed treatment on the basis of clinical recurrence . METHODS Women with ovarian cancer in complete remission after first-line platinum-based chemotherapy and a normal CA125 concentration were registered for this r and omised controlled trial . Clinical examination and CA125 measurement were done every 3 months . Patients and investigators were masked to CA125 results , which were monitored by coordinating centres . If CA125 concentration exceeded twice the upper limit of normal , patients were r and omly assigned ( 1:1 ) by minimisation to early or delayed chemotherapy . Patients and clinical sites were informed of allocation to early treatment , and treatment was started as soon as possible within 28 days of the increased CA125 measurement . Patients assigned to delayed treatment continued masked CA125 measurements , with treatment commencing at clinical or symptomatic relapse . All patients were treated according to st and ard local practice . The primary outcome was overall survival . Analysis was by intention to treat . This study is registered , IS RCT N87786644 . FINDINGS 1442 patients were registered for the trial , of whom 529 were r and omly assigned to treatment groups and were included in our analysis ( 265 early , 264 delayed ) . With a median follow-up of 56·9 months ( IQR 37·4 - 81·8 ) from r and omisation and 370 deaths ( 186 early , 184 delayed ) , there was no evidence of a difference in overall survival between early and delayed treatment ( HR 0·98 , 95 % CI 0·80 - 1·20 , p=0·85 ) . Median survival from r and omisation was 25·7 months ( 95 % CI 23·0 - 27·9 ) for patients on early treatment and 27·1 months ( 22·8 - 30·9 ) for those on delayed treatment . INTERPRETATION Our findings showed no evidence of a survival benefit with early treatment of relapse on the basis of a raised CA125 concentration alone , and therefore the value of routine measurement of CA125 in the follow-up of patients with ovarian cancer who attain a complete response after first-line treatment is not proven . FUNDING UK Medical Research Council and the European Organisation for Research and Treatment of Cancer OBJECTIVES To document levels of and changes in physical activity before and after ovarian cancer diagnosis and explore associations with psychosocial outcomes . METHODS Of 1207 eligible Australian Ovarian Cancer Study ( AOCS ) participants , 798 participated in an additional prospect i ve Quality of Life ( QoL ) Study which measured anxiety , depression and QoL at 3 - 6 monthly intervals for 2 years beginning 3 - 48 months after diagnosis . AOCS asked about physical activity before diagnosis and 530 women also completed a one-off lifestyle question naire 7 - 64 months after diagnosis which assessed activity during their first and , if relevant , second-to-third and fourth-to-sixth years following diagnosis . Analysis of variance was used to relate physical activity to psychosocial outcomes . RESULTS Almost 40 % of women decreased their physical activity in the first year after diagnosis . Approximately 25 % still had lower levels after 2 - 3 and 4+years . Recent physical activity level was inversely associated with depression and positively associated with QoL ( P<0.05 ) . Also , women who maintained or increased their physical activity after diagnosis had better mean depression and QoL scores than women who decreased physical activity or remained inactive ( P<0.05 ) . Among women who received chemotherapy shortly prior to completing the lifestyle question naire , high versus low or medium physical activity was associated with significantly lower mean depression scores during both periods of treatment and non-treatment ( P<0.05 ) . CONCLUSIONS Many women did not regain their pre-morbid physical activity levels several years after ovarian cancer diagnosis . Low physical activity may simply be a consequence of poor well-being but , alternatively , physical activity may improve psychosocial health of this group The objective of this study was to determine current practice with regards to follow-up after gynecological malignancy . A question naire survey of all lead clinicians in gynecological cancer centers in Engl and was done . The most common duration of routine follow-up was 5 years for all of the main gynecological cancers ( ovarian , endometrial , vulval , and cervical ) . The most common follow-up patterns were three monthly for 2 years then six monthly for 3 years after ovarian cancer ; three monthly for the first year , four monthly for the second year , six monthly for the third year then annually for 1 year after endometrial cancer ; three monthly for the first year , four monthly for the second year , six monthly for the third and fourth years , then annually for 1 year after vulval cancer ; three monthly for the first year , four monthly for the second year , six monthly for the third and fourth years , then annually for 1 year after cervical cancer . The test for CA125 was routinely performed by 67 % of cancer networks to detect recurrence after ovarian cancer . Routine follow-up after gynecological cancer continues to be st and ard practice , despite limited evidence to support its use . Prospect i ve research is needed to determine best practice Background : Women undergoing surgery for ovarian cancer are severely ill and are high users of health services . Contributing to these increased utilization rates are the multiple modalities used to treat ovarian cancer and the complications and side effects from those treatments . Objective : The purpose of this study was to evaluate the effectiveness of an intervention provided by advanced practice nurses and a psychiatric consultation-liaison nurse on patients ' self-report of healthcare utilization compared with an attention control intervention in women undergoing surgery for a suspected diagnosis of ovarian cancer . Methods : A two-group , experimental , longitudinal design was used to compare women who were assigned r and omly to the intervention group or to an attention control group at baseline within 48 hours after surgery and 1 , 3 , and 6 months after surgery . Healthcare utilization was measured as the number of self-reported inpatient admissions and outpatient visits , including emergency room visits , oncology outpatient visits , and primary care visits . Nurse interventions consisted of 16 contacts : symptom management , counseling , education , direct nursing care , coordination of re sources , and referrals . The attention control interventions consisted of nine contacts that included instructions on use of a symptom management toolkit and strategies on how to manage symptoms . Results : There were no differences in hospitalizations and oncology outpatient visits between the two groups . The main finding of this study was a significant difference in the number of primary care visits between the two groups . Women in the attention control group went to their primary care providers more often than the intervention group . The women who reported more visits also reported more depressive symptoms . In addition , a trend was found in the number of emergency room visits between the two groups . The intervention group visited the emergency room more often because the nurse instructed patients to go when they recognized symptoms that needed urgent care after hours . Discussion : Women in the intervention group appropriately used the emergency room to manage their problems after hours , whereas more women in the attention control group reported significantly more primary care visits . These findings highlight the need for healthcare providers representing various disciplines to coordinate services across specialties , especially for women who have depressive symptoms OBJECTIVE The aim of this study was to assess the long-term impact of an automatically generated Survivorship Care Plan ( SCP ) on patient reported outcomes in ovarian cancer in routine clinical practice . Outcome measures included satisfaction with information provision and care , illness perceptions and health care utilization . METHODS In this pragmatic cluster r and omized trial , twelve hospitals in the South of the Netherl and s were r and omized to ' SCP care ' or ' usual care ' . All newly diagnosed ovarian cancer patients in the ' SCP care ' arm received an SCP that was automatically generated by the oncology provider , by clicking a button in the web-based Registration system Oncological GYnecology ( ROGY ) . Ovarian cancer patients ( N=174 , mean age 63.3 , SD=11.4 ; all stages ) completed question naires directly after initial treatment and after 6 , 12 and 24months . RESULTS First question naires were returned from 61 ( 67 % ) ovarian cancer patients in the ' SCP care ' arm and 113 ( 72 % ) patients in the ' usual care ' arm . In the ' SCP care ' arm , 66 % ( N=41 ) of the patients reported receipt of an SCP . No overall differences were observed between the trial arms on satisfaction with information provision , satisfaction with care or health care utilization . Regarding illness perceptions , patients in the ' SCP care ' arm had lower beliefs that the treatment would help to cure their disease ( overall , 6.7 vs. 7.5 , P<0.01 ) . CONCLUSIONS SCPs did not increase satisfaction with information provision or care in ovarian cancer patients . Our trial results suggest that ovarian cancer patients may not benefit from an SCP . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01185626 This study defines the psychometric properties of the European Organisation for Research and Treatment of Cancer ( EORTC ) quality of life ( QOL ) question naire design ed to measure the QOL of patients with ovarian cancer . The ovarian cancer module ( EORTC QLQ-OV28 ) was developed to supplement the EORTC QLQ-C30 . The core question naire and the QLQ-OV28 were prospect ively administered to 368 ovarian cancer patients after they had been treated with radical or debulking surgery followed by chemotherapy . The QLQ-OV28 module assesses abdominal/gastrointestinal symptoms , peripheral neuropathy , other chemotherapy side-effects , hormonal/menopausal symptoms , body image , attitude to disease/treatment and sexual functioning . Question naires were well accepted by patients , baseline compliance rates were 86 % , 72 % provided a second assessment , less than 3 % of the items had missing data . Multi-trait scaling analyses confirmed the hypothesised scales . All hypothesised scales exhibited good psychometric properties . These results support the clinical and psychometric validity of the EORTC QLQ-OV28 module as a supplement to the EORTC QLQ-C30 PURPOSE To develop and pilot test an intervention targeting the women 's psychosocial needs during the follow-up period after surgical treatment for gynaecological cancer . METHODS The project consisted of four phases . Phase 1 involved development of an intervention on the basis of meetings with key healthcare professionals , a literature review and six semi-structured interviews with women who attended the existing follow-up program . The Guided Self-Determination ( GSD ) method developed in diabetes care was identified as an appropriate framework for the intervention . GSD consists of reflection sheets for patients and advanced professional communication skills . The GSD method was adapted to women in a follow-up program after gynaecologic cancer treatment ( GSD-GYN-C ) . Phase 2 involved primary pilot testing of the intervention and the findings were used to modify the intervention in phase 3 . This modification involved the development of additional reflection sheets and a fidelity assessment tool . A systematic training program was arranged for the GSD-GYN-C-nurses . Phase 4 involved secondary pilot testing where nurses and women confirmed the applicability of GSD-GYN-C and final adjustments were made . Selected measurements were tested for sensitivity during pilot testing . Data from phase 2 and 4 were also used to select the primary outcome and calculate power for a future r and omized clinical trial ( RCT ) . RESULTS Pilot testing supported our hypothesis that GSD-GYN-C may be transferable and useful to survivors of gynaecological cancer . CONCLUSION GSD-GYN-C was developed and vali date d and is now ready for evaluation in an RCT PURPOSE To examine the effects on process of care and patient well-being , of the regular collection and use of health-related quality -of-life ( HRQL ) data in oncology practice . PATIENTS AND METHODS In a prospect i ve study with repeated measures involving 28 oncologists , 286 cancer patients were r and omly assigned to either the intervention group ( regular completion of European Organization for Research and Treatment of Cancer-Core Quality of Life Question naire version 3.0 , and Hospital Anxiety and Depression Scale on touch-screen computers in clinic and feedback of results to physicians ) ; attention-control group ( completion of question naires , but no feedback ) ; or control group ( no HRQL measurement in clinic before encounters ) . Primary outcomes were patient HRQL over time , measured by the Functional Assessment of Cancer Therapy-General question naire , physician-patient communication , and clinical management , measured by content analysis of tape-recorded encounters . Analysis employed mixed-effects modeling and multiple regression . RESULTS Patients in the intervention and attention-control groups had better HRQL than the control group ( P = .006 and P = .01 , respectively ) , but the intervention and attention-control groups were not significantly different ( P = .80 ) . A positive effect on emotional well-being was associated with feedback of data ( P = .008 ) , but not with instrument completion ( P = .12 ) . A larger proportion of intervention patients showed clinical ly meaningful improvement in HRQL . More frequent discussion of chronic nonspecific symptoms ( P = .03 ) was found in the intervention group , without prolonging encounters . There was no detectable effect on patient management ( P = .60 ) . In the intervention patients , HRQL improvement was associated with explicit use of HRQL data ( P = .016 ) , discussion of pain , and role function ( P = .046 ) . CONCLUSION Routine assessment of cancer patients ' HRQL had an impact on physician-patient communication and result ed in benefits for some patients , who had better HRQL and emotional functioning The current study evaluated the efficacy of incorporating st and ardized health‐related quality of life ( HRQL ) assessment s as a routine part of the outpatient chemotherapy treatment of cancer patients in a community hospital in terms of : 1 ) facilitating nurse‐patient communication , 2 ) increasing nurses ' awareness of patients ' HRQL , 3 ) patient management , 4 ) patients ' satisfaction , and 5 ) patients ' HRQL |
13,855 | 24,018,460 | Self-help may be useful for people who are not able or are not willing to use other services for people with anxiety disorders ; for people who can access it , face-to-face cognitive behavioural therapy is probably clinical ly superior .
Recent interventions for specific problems that incorporate clinician support may be more effective than transdiagnostic interventions ( i.e. interventions for multiple disorders ) provided with no guidance , but these issues are confounded in the available trials . | BACKGROUND Anxiety disorders are the most common mental health problems .
They are chronic and unremitting .
Effective treatments are available , but access to services is limited .
Media-delivered behavioural and cognitive behavioural interventions ( self-help ) aim to deliver treatment with less input from professionals compared with traditional therapies .
OBJECTIVES To assess the effects of media-delivered behavioural and cognitive behavioural therapies for anxiety disorders in adults .
Self-help has been recommended as the first step in the treatment of some anxiety disorders , but the short-term and long-term effectiveness of media-delivered interventions has not been established . | Background and Aims Cognitive behavioral group therapy ( CBGT ) is an effective , well-established , but not widely available treatment for social anxiety disorder ( SAD ) . Internet-based cognitive behavior therapy ( ICBT ) has the potential to increase availability and facilitate dissemination of therapeutic services for SAD . However , ICBT for SAD has not been directly compared with in-person treatments such as CBGT and few studies investigating ICBT have been conducted in clinical setting s. Our aim was to investigate if ICBT is at least as effective as CBGT for SAD when treatments are delivered in a psychiatric setting . Methods We conducted a r and omized controlled non-inferiority trial with allocation to ICBT ( n = 64 ) or CBGT ( n = 62 ) with blinded assessment immediately following treatment and six months post-treatment . Participants were 126 individuals with SAD who received CBGT or ICBT for a duration of 15 weeks . The Liebowitz Social Anxiety Scale ( LSAS ) was the main outcome measure . The following non-inferiority margin was set : following treatment , the lower bound of the 95 % confidence interval ( CI ) of the mean difference between groups should be less than 10 LSAS-points . Results Both groups made large improvements . At follow-up , 41 ( 64 % ) participants in the ICBT group were classified as responders ( 95 % CI , 52%–76 % ) . In the CBGT group , 28 participants ( 45 % ) responded to the treatment ( 95 % CI , 33%–58 % ) . At post-treatment and follow-up respectively , the 95 % CI of the LSAS mean difference was 0.68–17.66 ( Cohen ’s d between group = 0.41 ) and −2.51–15.69 ( Cohen ’s d between group = 0.36 ) favoring ICBT , which was well within the non-inferiority margin . Mixed effects models analyses showed no significant interaction effect for LSAS , indicating similar improvement across treatments ( F = 1.58 ; df = 2 , 219 ; p = .21 ) . Conclusions ICBT delivered in a psychiatric setting can be as effective as CBGT in the treatment of SAD and could be used to increase availability to CBT . Trial Registration Clinical Trials.gov In web-based health promotion programs , large variations in participant engagement are common . The aim was to investigate determinants of high use of a worksite self-help web-based program for stress management . Two versions of the program were offered to r and omly selected departments in IT and media companies . A static version of the program including health screening tool , diary and information about stress was offered to the control group . Additional material s , i.e. interactive , cognitive-based and classical stress management exercises and a chat room , were offered to the intervention group . Baseline data regarding participants ' demographics , health ( self-ratings and biological measures ) , lifestyle , work-related factors and group membership were analyzed to study determinants of employees ' participation in the program during a period of 12 months . Multiple logistic regression analysis was used and found intervention group membership , being a woman , having at most a secondary education , regular physical exercise habits and having positive expectations of the program were significant predictors of high use . The findings demonstrate that the interactivity of a web-based program is an important factor for determining participation in a web-based worksite stress management program . Implication s for those developing and implementing future web-based health promotion activities are discussed Background Social anxiety disorder ( SAD ) is one of the most common anxiety disorders and is associated with marked impairments . However , a small proportion of individuals with SAD seek and receive treatment . Internet-administrated cognitive behavior therapy ( iCBT ) has been found to be an effective treatment for SAD . This trial will be the first Internet-delivered guided self-help intervention for SAD in Romania . Methods Participants with social anxiety disorder ( N = 96 ) will be recruited via newspapers , online banners and Facebook . Participants will be r and omized to either : a ) an active treatment , or b ) a waiting list control group . The treatment will have a guided iCBT format and will last for nine weeks . Self-report question naires on social phobia , anxiety , depression , treatment credibility and irrational thinking will be used . All assessment s will be collected pre , post and at follow-up ( six months after intervention ) . Liebowitz Social Anxiety Scale – Self-Report version ( LSAS-SR ) will be the primary outcome measure and will be administrated on a weekly basis in both conditions . Discussion The present r and omized controlled trial investigates the efficacy of an Internet-administered intervention in reducing social anxiety symptoms in a culture where this form of treatment has not been tested . This trial will add to the body of knowledge on the efficacy of iCBT , and the results might lead to an increase of the accessibility of evidence -based psychological treatment in Romania . Trial registration Clinical Trials.gov : The mental health challenges of some vocations present a challenge for current intervention models . Bibliotherapy focused on transdiagnostic processes that might both prevent and alleviate a range of mental health distress could be an effective and practical approach . K-12 school personnel ( N = 236 ; 91 % female ; 30 - 60 years old ) responding to a wellness-oriented program announcement were r and omized to receive an Acceptance and Commitment Therapy ( ACT ) self-help volume or to a waitlist . Three-fourths were above clinical cutoffs in general mental health , depression , anxiety , or stress . Participants read the book for two months , completed exercises and quizzes , and after post assessment were followed for 10 weeks ; waitlist participants were then also given the book with two months to complete it . Overall , participants showed significant improvement in psychological health . Significant preventive effects for depression and anxiety were observed along with significant ameliorative effects for those in the clinical ranges of depression , anxiety and stress . Follow up general mental health , depression , and anxiety outcomes were related to the manner in which participants used the workbook and to post levels of psychological flexibility Bibliotherapy is potentially effective in the treatment of panic disorder ( PD ) . A still unanswered question is whether pacing is important . This study was design ed to test whether there is a difference between being assigned a full book as therapy and receiving one individual chapter every week ( i.e. pacing ) . A total of 28 participants were r and omized to either 10 paced chapters or one book with 10 chapters . To maximize compliance , short weekly telephone calls were added in both conditions ( M = 17.8 min , SD = 4.2 ) . Both treatments showed promising results , with effects maintained up to 2 years and with within-group effect sizes ( Cohen 's d ) between 0.95 and 1.11 . Pretreatment ratings of credibility were positively correlated with the change scores at both posttest and 2-year follow-up for three panic measures . Pacing of text material in bibliotherapy for PD is not needed , and all material can be provided at once when the treatment is guided by a therapist BACKGROUND Although effective therapies for social phobia exist , many individuals refrain from seeking treatment owing to the embarrassment associated with help-seeking . Internet-based cognitive-behavioural self-help can be an alternative , but adherence is a problem . AIMS To evaluate a 9-week programme of internet-based therapy design ed to increase treatment adherence by the addition of short weekly telephone calls , nine in all , with a total duration of 95 min . METHOD In a r and omised controlled trial the effects of internet-based cognitive-behavioural therapy in the treatment group ( n=29 ) were compared with a waiting-list control group ( n=28 ) . RESULTS Compared with the control group the treated participants experienced greater reductions on measures of general and social anxiety , avoidance and depression . Adherence to treatment was high , with 93 % finishing the complete treatment package . One year later all improvements were maintained . CONCLUSIONS This study provides evidence to support the use of internet-based treatment supplemented by short , weekly telephone calls Objective : This study aim ed to compare the effectiveness of computerised cognitive behaviour therapy ( CCBT ) with a wait list control ( WLC ) for the treatment of patients with an anxiety disorder ( social phobia , panic disorder , generalised anxiety disorder ) referred to a specialist , publically funded , outpatient anxiety service . Method : Patients with social phobia ( n = 37 ) , panic disorder ( n = 32 ) or generalised anxiety disorder ( n = 14 ) were r and omised to treatment with either CCBT ( n = 40 ) or WLC ( n = 43 ) . Self-report rating scale assessment s were conducted at baseline , 12 and 24 weeks . Results : Compared with WLC , the CCBT group improved significantly on approximately half of the self-report primary ( the Work and Social Adjustment Scale ) and approximately half of the secondary measures at both 12 and 24 weeks ( the Liebowitz Social Anxiety Scale , the Penn State Worry Question naire , the Generalised Anxiety inventory and the Fear Question naire ) . Effect sizes in this study were moderate . Conclusion : This is one of the few studies to investigate CCBT for anxiety disorders in patients in a secondary care service . The results show that CCBT in this secondary care setting has the potential to be beneficial and confirms and extends the findings from previous studies of self-referral or primary care setting Background Phobic disorders are highly prevalent and constitute a considerable burden for patients and society . As patients wait for face-to-face psychotherapy for phobic disorders in outpatient clinics , this time can be used for guided self-help interventions . The aim of this study is to investigate a five week internet-based guided self-help programme of exposure therapy in terms of clinical effectiveness and impact on speed of recovery in psychiatric out patients , as well as the cost-effectiveness of this pre-treatment waiting list intervention . Methods / design A r and omised controlled trial will be conducted among 244 Dutch adult patients recruited from waiting lists of outpatient clinics for face-to-face psychotherapy for phobic disorders . Patients suffering from at least one DSM-IV classified phobic disorder ( social phobia , agoraphobia or specific phobia ) are r and omly allocated ( at a 1:1 ratio ) to either a five-week internet-based guided self-help program followed by face-to-face psychotherapy , or a control group followed by face-to-face psychotherapy . Waiting list status and duration are unchanged and actual need for further treatment is evaluated prior to face-to-face psychotherapy . Clinical and economic self- assessment measurements take place at baseline , post-test ( five weeks after baseline ) and at 3 , 6 , 9 and 12 months after baseline . Discussion Offering pre-treatment internet-based guided self-help efficiently uses time otherwise lost on a waiting list and may increase patient satisfaction . Patients are expected to need fewer face-to-face sessions , reducing total treatment cost and increasing speed of recovery . Internet-delivered treatment for phobias may be a valuable addition to psychotherapy as dem and for outpatient treatment increases while budgets decrease . Trial registration Netherl and s Trial Register Background Internet support groups ( ISGs ) are popular , particularly among people with depression , but there is little high quality evidence concerning their effectiveness . Aim The study aim ed to evaluate the efficacy of an ISG for reducing depressive symptoms among community members when used alone and in combination with an automated Internet-based psychotherapy training program . Method Volunteers with elevated psychological distress were identified using a community-based screening postal survey . Participants were r and omised to one of four 12-week conditions : depression Internet Support Group ( ISG ) , automated depression Internet Training Program ( ITP ) , combination of the two ( ITP+ISG ) , or a control website with delayed access to e-couch at 6 months . Assessment s were conducted at baseline , post-intervention , 6 and 12 months . Results There was no change in depressive symptoms relative to control after 3 months of exposure to the ISG . However , both the ISG alone and the combined ISG+ITP group showed significantly greater reduction in depressive symptoms at 6 and 12 months follow-up than the control group . The ITP program was effective relative to control at post-intervention but not at 6 months . Conclusions ISGs for depression are promising and warrant further empirical investigation . Trial Registration Controlled-Trials.com IS RCT BRUCE BAKERHarvard UniversityPhobic Ss were r and omly assigned to 1 of 2 treatment groups : ( 1 ) a " conven-tional desensitization " group , which was treated by a therapist in the labora-tory , or ( 2 ) a " do-it-yourself " group , which carried out the desensitizationprocess at home . For the latter , the only therapist contact was an initialinterview and a weekly progress-check phone call . According to Ss ' reportsof success , both groups did equally well . These results are discussed withrespect to the relative importance of relationship and content in the therapeuticprocess Background Interventions to promote mental well-being can bring benefits to the individual and to society . The Internet can facilitate the large-scale and low-cost delivery of individually targeted health promoting interventions . Objective To evaluate the effectiveness of a self-directed Internet-delivered cognitive-behavioral skills training tool in improving mental well-being in a population sample . Methods This was a r and omized trial with a waiting-list control . Using advertisements on a national health portal and through its mailing list , we recruited 3070 participants aged 18 or over , resident in Engl and , and willing to give their email address and access a fully automated Web-based intervention . The intervention ( MoodGYM ) consisted of 5 interactive modules that teach cognitive-behavioral principles . Participants in the intervention arm received weekly email reminders to access the intervention . The control group received access to the intervention after the trial was completed and received no specific intervention or email reminders . Outcomes were assessed by using self-completion question naires . The primary outcome was mental well-being measured with the Warwick-Edinburgh Mental Well-being Scale ( WEMWBS ) . Secondary outcomes were Center for Epidemiologic Studies Depression scale ( CES-D ) depression scores , Generalized Anxiety Disorder 7-item scale ( GAD-7 ) anxiety scores , EuroQol Group 5-Dimension Self-Report Question naire ( EQ-5D ) quality of life scores , physical activity , and health service use . All outcomes were measured at baseline , and at 6- and 12-week follow-ups . Results A total of 1529 ( 49.80 % ) participants completed final follow-up at 12 weeks . Retention was 73.11 % ( 1123/1536 ) in the control arm and 26.47 % ( 406/1534 ) in the intervention arm . No relationship between baseline measures and withdrawal could be established . The analysis of WEMWBS mental well-being scores using a linear mixed model for repeated measures showed no difference between intervention and control group at baseline ( difference –0.124 points , 95 % CI –0.814 to 0.566 ) , and significant improvements for the intervention group at 6 weeks ( 2.542 points , 95 % CI 1.693 - 3.390 ) and at 12 weeks ( 2.876 points , 95 % CI 1.933 - 3.819 ) . The model showed a highly significant ( P<.001 ) intervention by time interaction effect . There were also significant improvements in self-rated scores of depression and anxiety . Given the high level of attrition , a sensitivity analysis with imputed missing values was undertaken that also showed a significant positive effect of the intervention . Conclusions Participants allocated to the intervention arm had an average increase of approximately 3 points on the WEMWBS scale compared to no increase for participants in the control group . Three points on this scale is approximately one-third of a st and ard deviation . In a low-cost automated intervention design ed to shift the population distribution of mental well-being , a small difference per individual could yield a major benefit in population terms . In common with other Web-based interventions , there were high rates of attrition . Further work is needed to improve acceptability , to evaluate against placebo effect , and to disaggregate the effect on mental well-being from the effect on depression and anxiety . Trial Registration International St and ard R and omised Controlled Trial Number Register IS RCT N 48134476 ; http://www.controlled-trials.com/IS RCT N48134476 ( Archived by WebCite ® at http://www.webcitation.org/6DFgW2p3Q Background Self-help therapies are often effective in reducing mental health problems . We developed a new Web-based self-help intervention based on problem-solving therapy , which may be used for people with different types of comorbid problems : depression , anxiety , and work-related stress . Objective The aim was to study whether a Web-based self-help intervention is effective in reducing depression , anxiety , and work-related stress ( burnout ) . Methods A total of 213 participants were recruited through mass media and r and omized to the intervention ( n = 107 ) or a waiting list control group ( n = 106 ) . The Web-based course took 4 weeks . Every week an automated email was sent to the participants to explain the contents and exercises for the coming week . In addition , participants were supported by trained psychology students who offered feedback by email on the completed exercises . The core element of the intervention is a procedure in which the participants learn to approach solvable problems in a structured way . At pre-test and post-test , we measured the following primary outcomes : depression ( CES-D and MDI ) , anxiety ( SCL-A and HADS ) , and work-related stress ( MBI ) . Quality of life ( EQ-5D ) was measured as a secondary outcome . Intention-to-treat analyses were performed . Results Of the 213 participants , 177 ( 83.1 % ) completed the baseline and follow-up question naires ; missing data were statistically imputed . Of all 107 participants in the intervention group , 9 % ( n = 10 ) dropped out before the course started and 55 % ( n = 59 ) completed the whole course . Among all participants , the intervention was effective in reducing symptoms of depression ( CES-D : Cohen ’s d = 0.50 , 95 % confidence interval ( CI ) 0.22 - 0.79 ; MDI : d = 0.33 , 95 % CI 0.03 - 0.63 ) and anxiety ( SCL-A : d = 0.42 , 95 % CI 0.14 - 0.70 ; HADS : d = 0.33 , 95 % CI 0.04 - 0.61 ) as well as in enhancing quality of life ( d = 0.31 , 95 % CI 0.03 - 0.60 ) . Moreover , a higher percentage of patients in the intervention group experienced a significant improvement in symptoms ( CES-D : odds ratio [ OR ] = 3.5 , 95 % CI 1.9 - 6.7 ; MDI : OR = 3.7 , 95 % CI 1.4 - 10.0 ; SCL-A : OR = 2.1 , 95 % CI 1.0 - 4.6 ; HADS : OR = 3.1 , 95 % CI 1.6 - 6.0 ) . Patients in the intervention group also recovered more often ( MDI : OR = 2.2 ; SCL-A : OR = 2.0 ; HADS < 8) , although these results were not statistically significant . The course was less effective for work-related stress , but participants in the intervention group recovered more often from burnout than those in the control group ( OR = 4.0 , 95 % CI 1.2 - 13.5 ) . Conclusions We demonstrated statistically and clinical ly significant effects on symptoms of depression and anxiety . These effects were even more pronounced among participants with more severe baseline problems and for participants who fully completed the course . The effects on work-related stress and quality of life were less clear . To our knowledge , this is the first trial of a Web-based , problem-solving intervention for people with different types of ( comorbid ) emotional problems . The results are promising , especially for symptoms of depression and anxiety . Further research is needed to enhance the effectiveness for work-related stress . Trial Registration International St and ard R and omized Controlled Trial Number ( IS RCT N ) Background Previous studies on Internet-based treatment with minimal therapist guidance have shown promising results for several specific diagnoses . Objective To ( 1 ) investigate the effects of a tailored , therapist-guided , Internet-based treatment for individuals with reoccurring panic attacks , and ( 2 ) to examine whether people in different age groups ( 18–30 years and 31–45 years ) would respond differently to the treatment . Methods We recruited 149 participants from an online list of individuals having expressed an interest in Internet treatment . Screening consisted of online question naires followed by a telephone interview . A total of 57 participants were included after a semistructured diagnostic interview , and they were r and omly assigned to an 8-week treatment program ( n = 29 ) or to a control condition ( n = 28 ) . Treatment consisted of individually prescribed cognitive behavior therapy text modules in conjunction with online therapist guidance . The control group consisted of people on a waitlist who later received treatment . Results All dependent measures improved significantly immediately following treatment and at the 12-month follow-up . The between-group effect size on the primary outcome measure , the Panic Disorder Severity Scale , was d = 1.41 ( 95 % confidence interval 0.81–1.95 ) at posttreatment . The within-group effect size from pretreatment to 12-month follow-up was d = 1.66 ( 95 % confidence interval 1.14–2.35 ) . Age group had no effect , suggesting that age did not influence the outcome . Conclusions Tailoring an Internet-based treatment can be a feasible approach in the treatment of panic symptoms and comorbid anxiety and depressive symptoms . Younger adults benefit as much as adults over 30 years and up to 45 years of age . Trial Registration Clinical trials.gov NCT01296321 ; http://www . clinical trials.gov/ct2/show/NCT01296321 ( Archived by WebCite at http://www.webcitation.org/65wddsqlL BACKGROUND Exposure and response prevention ( ERP ) for obsessive-compulsive disorder ( OCD ) is underutilized , in part because of costs and time requirements . This study extends pilot work investigating the use of a stepped care ERP administration , in which patients are first given a low-intensity , low-cost treatment and the more costly intervention is reserved for those who do not respond to the first intervention . METHODS Thirty adults with OCD were r and omized to receive stepped care ERP or st and ard ERP . Those receiving stepped care started with three sessions over 6 weeks of low-intensity counseling with ERP bibliotherapy ; patients failing to meet strict responder criteria after 6 weeks were given the more traditional treatment of therapist-administered ERP ( 17 sessions twice weekly ) . Those receiving st and ard ERP received the therapist-administered ERP with no lower-intensity lead-in . RESULTS The two treatments were equally efficacious , with 67 % of stepped care completers and 50 % of st and ard treatment completers meeting criteria for clinical ly significant change at posttreatment . Similarly , no differences in client satisfaction ratings were obtained between the two groups . Examination of treatment costs , however , revealed that stepped care result ed in significantly lower costs to patients and third-party payers than did st and ard ERP , with large effect sizes . CONCLUSIONS These results suggest that stepped care ERP can significantly reduce treatment costs , without evidence of diminished treatment efficacy or patient satisfaction . Additional research is needed to determine the long-term efficacy and costs of stepped care for OCD , and to examine the financial and therapeutic impact of implementing stepped care in community setting BACKGROUND Internet-delivered self-help programmes with added therapist guidance have shown efficacy in social anxiety disorder , but unguided self-help has been insufficiently studied . AIMS To evaluate the efficacy of guided and unguided self-help for social anxiety disorder . METHOD Participants followed a cognitive-behavioural self-help programme in the form of either pure bibliotherapy or an internet-based treatment with therapist guidance and online group discussion s. A subsequent trial was conducted to evaluate treatment specificity . Participants ( n = 235 ) were r and omised to one of three conditions in the first trial , or one of four conditions in the second . RESULTS Pure bibliotherapy and the internet-based treatment were better than waiting list on measures of social anxiety , general anxiety , depression and quality of life . The internet-based therapy had the highest effect sizes , but directly comparable effects were noted for bibliotherapy augmented with online group discussion s. Gains were well maintained a year later . CONCLUSIONS Unguided self-help through bibliotherapy can produce enduring improvement for individuals with social anxiety disorder Patients with phobic disorder ( mainly agoraphobics ) of minimum one year duration were treated by self-administered exposure in vivo treatment . Seventy-one patients were r and omly assigned to one of three groups : ( A ) book-instructed , ( B ) computer-instructed , or ( C ) therapist-instructed . All three groups improved significantly to a similar extent on various phobic measures at the end of the treatment and maintained their treatment gains at 6-month follow up . Mean clinicians ' time spent with each patient was 40 minutes , 4.2 hours and 3.2 hours in group A , B and C respectively . Similar small numbers of patients defaulted from each group This paper describes CARL ( Computer Assisted Relaxation Learning ) , a computerized , exposure-based therapy program for the treatment of dental injection fear . The CARL program operates primarily in two different modes ; in vitro , which presents a video-taped exposure hierarchy , and in vivo , which presents scripts for a dentist or hygienist to use while working with a subject . Two additional modes are used to train subjects to use the program and to administer behavioral assessment tests . The program contains five different modules , which function to register a subject , train subjects to use physical and cognitive relaxation techniques , deliver an exposure hierarchy , question subjects about the helpfulness of each of the therapy components , and test for memory effects of anxiolytic medication . Nine subjects have completed the CARL therapy program and 1-yr follow-up as participants in a placebo-controlled clinical trial examining the effects of alprazolam on exposure therapy for dental injection phobia . All nine subjects were able to receive two dental injections , and all reduced their general fear of dental injections . Initial results therefore indicate that the CARL program successfully reduces dental injection fear Twenty-eight individuals with panic disorder were provided with a copy of Mastery of Your Anxiety and Panic II and received either four sessions of group cognitive-behavior therapy ( Group ) or one meeting with a therapist plus three telephone contacts ( Telephone ) . Between group repeated measures analyses revealed significant improvement over the course of treatment and maintenance of gains over the follow-up period with few treatment by trials interactions . A higher percentage of participants in the Telephone condition achieved high end-state functioning status at posttreatment compared to those who participated in group CBT ( 72 % vs. 24 % ) , but this difference disappeared at 6 months posttreatment ( 45 % vs. 55 % ) . Participants with characteristics of either borderline , dependent , or depressive personality disorders , as assessed by the MCMI-III , were unlikely to achieve high end-state functioning status at posttreatment . Trends in the data suggest that participants who met criteria for panic disorder with agoraphobia , and those with comorbid generalized anxiety disorder , were also less likely to achieve clinical ly significant outcome . These findings add to the growing literature indicating that self-directed treatment with brief therapist contact is a viable option for many people with panic disorder . Furthermore , the study provides preliminary data suggesting that certain comorbid conditions negatively impact self-directed treatment outcome Despite its high prevalence and implication s for health care re sources , health anxiety is generally considered difficult and expensive to manage . Structured self-help material s ( bibliotherapy ) using a cognitive behaviour therapy ( CBT ) treatment approach have been shown to be clinical ly effective . This experimental study investigated the effects of bibliotherapy on patients who had been identified as demonstrating health concerns . The 40 participants ( patients drawn from GP surgeries ) were r and omly allocated to two groups , one receiving bibliotherapy and the other not . Half the patients had a medically diagnosed problem . Anxiety was assessed before and after the bibliotherapy intervention , which took the form of a cognitive-behavioural self-help booklet for health anxiety sufferers . Patients in the bibliotherapy group showed reduced levels of anxiety at post-test , even when they also had an identifiable physical problem . These results are consistent with the idea that self-help material s can be an effective and accessible intervention in CBT , although further research is recommended BACKGROUND Panic disorder , with and without agoraphobia , is a prevalent condition presenting in general practice . Psychological treatments are effective but are limited by restricted availability . Interest has grown in methods by which the efficiency and thus availability of psychological treatments can be improved , with particular emphasis on reduced therapist contact formats . AIM To evaluate the relative efficacy in a primary care setting of a cognitive behaviour therapy ( CBT ) delivered at three levels of therapist contact : st and ard contact , minimum contact , and bibliotherapy . METHOD A total of 104 patients were r and omly allocated to receive st and ard therapist contact , minimum therapist contact or bibliotherapy , with 91 patients completing treatment . All patients received an identical treatment manual and were seen by the same psychologist therapist . Outcome was reported in terms of brief global ratings of severity of illness , change in symptoms , and levels of social disruption . These brief measures were chosen to be suitable for use in general practice and were used at treatment entry and endpoint . RESULTS The st and ard therapist contact group had the strongest and most comprehensive treatment response , showing significant differences from the bibliotherapy group on all , and the minimum therapist contact group on some , endpoint measures . Some reduction in efficacy was therefore found for the reduced therapist contact groups . CONCLUSION The st and ard therapist contact group showed the greatest treatment efficacy in the present study . As it was of notably shorter duration than many other current formulations of CBT , it represents a useful and efficient treatment for panic disorder and agoraphobia in primary care Background Panic disorder ( PD ) and generalized anxiety disorder ( GAD ) are two of the most disabling and costly anxiety disorders seen in primary care . However , treatment quality of these disorders in primary care generally falls beneath the st and ard of international guidelines . Collaborative stepped care is recommended for improving treatment of anxiety disorders , but cost-effectiveness of such an intervention has not yet been assessed in primary care . This article describes the aims and design of a study that is currently underway . The aim of this study is to evaluate effects and costs of a collaborative stepped care approach in the primary care setting for patients with PD and GAD compared with care as usual . Methods / design The study is a two armed , cluster r and omized controlled trial . Care managers and their primary care practice s will be r and omized to deliver either collaborative stepped care ( CSC ) or care as usual ( CAU ) . In the CSC group a general practitioner , care manager and psychiatrist work together in a collaborative care framework . Stepped care is provided in three steps : 1 ) guided self-help , 2 ) cognitive behavioral therapy and 3 ) antidepressant medication . Primary care patients with a DSM-IV diagnosis of PD and /or GAD will be included . 134 completers are needed to attain sufficient power to show a clinical ly significant effect of 1/2 SD on the primary outcome measure , the Beck Anxiety Inventory ( BAI ) . Data on anxiety symptoms , mental and physical health , quality of life , health re source use and productivity will be collected at baseline and after three , six , nine and twelve months . Discussion It is hypothesized that the collaborative stepped care intervention will be more cost-effective than care as usual . The pragmatic design of this study will enable the research ers to evaluate what is possible in real clinical practice , rather than under ideal circumstances . Many requirements for a high quality trial are being met . Results of this study will contribute to treatment options for GAD and PD in the primary care setting . Results will become available in 2011.Trial registration OBJECTIVE The aim of the present study was to compare the effectiveness and acceptability of three interventions for occupational stress . METHODS / DESIGN A total of 90 National Health Service employees were r and omized to face-to-face counselling or telephone counselling or bibliotherapy . Outcomes were assessed at post-intervention and 4-month follow-up . Clinical Outcomes in Routine Evaluation ( CORE ) , General Health Question naire ( GHQ-12 ) , and Perceived Stress Scale ( PSS-10 ) were used to evaluate intervention outcomes . An intention-to-treat analyses was performed . RESULTS Repeated measures analysis revealed significant time effects on all measures with the exception of CORE Risk . No significant group effects were detected on all outcome measures . No time by group significant interaction effects were detected on any of the outcome measures with the exception of CORE Functioning and GHQ total . With regard to acceptability of interventions , participants expressed a preference for face-to-face counselling over the other two modalities . CONCLUSIONS Overall , it was concluded that the three intervention groups are equally effective . Given that bibliotherapy is the least costly of the three , results from the present study might be considered in relation to a stepped care approach to occupational stress management with bibliotherapy as the first line of intervention , followed by telephone and face-to-face counselling as required Recent theoretical models of social phobia suggest that targeting several specific cognitive factors in treatment should enhance treatment efficacy over that of more traditional skills-based treatment programs . In the current study , 195 people with social phobia were r and omly allocated to 1 of 3 treatments : st and ard cognitive restructuring plus in vivo exposure , an " enhanced " treatment that augmented the st and ard program with several additional treatment techniques ( e.g. , performance feedback , attention retraining ) , and a nonspecific ( stress management ) treatment . The enhanced treatment demonstrated significantly greater effects on diagnoses , diagnostic severity , and anxiety during a speech . The specific treatments failed to differ significantly on self-report measures of social anxiety symptoms and life interference , although they were both significantly better than the nonspecific treatment . The enhanced treatment also showed significantly greater effects than st and ard treatment on 2 putative process measures : cost of negative evaluation and negative views of one 's skills and appearance . Changes on these process variables mediated differences between the treatments on changes in diagnostic severity BACKGROUND Preliminary results have demonstrated the clinical efficacy of computerised cognitive-behavioural therapy ( CBT ) in the treatment of anxiety and depression in primary care . AIMS To determine , in an exp and ed sample , the dependence of the efficacy of this therapy upon clinical and demographic variables . METHOD A sample of 274 patients with anxiety and /or depression were r and omly allocated to receive , with or without medication , computerised CBT or treatment as usual , with follow-up assessment at 6 months . RESULTS The computerised therapy improved depression , negative attributional style , work and social adjustment , without interaction with drug treatment , duration of preexisting illness or severity of existing illness . For anxiety and positive attributional style , treatment interacted with severity such that computerised therapy did better than usual treatment for more disturbed patients . Computerised therapy also led to greater satisfaction with treatment . CONCLUSIONS Computer-delivered CBT is a widely applicable treatment for anxiety and /or depression in general practice BACKGROUND The dem and for time-consuming psychotherapy of phobia/panic exceeds the supply of trained therapists . Delegating routine therapy aspects to a computer might ease this problem . METHOD Ninety-three out- patients with phobia or panic disorder were r and omized in a 2 : 2 : 1 ratio to have self-exposure therapy guided either mainly by a st and -alone computer system ( FearFighter ) or entirely face-to-face by a clinician , or to have mainly computer-guided self-relaxation as a placebo . Both computer groups ( FearFighter and relaxation ) had brief back-up advice from a clinician . Primary outcome measures were self- and blind-assessor ratings of Main Problem and Goals , and Global Phobia . RESULTS Drop-outs occurred significantly more often in the two self-exposure groups ( 43 % if mainly computer-guided , 24 % if entirely clinician-guided ) than with self-relaxation ( 6 % ) ; the difference between the two self-exposure groups was not significant . Even with all drop-outs included , the mainly computer-guided exposure group and the relaxation group had 73 % less clinician time per patient than did the entirely clinician-guided exposure group . The two self-exposure groups had comparable improvement and satisfaction at post-treatment and at 1-month follow-up , while relaxation was ineffective . Mean improvement on the primary outcome measures ( self- and assessor-rated ) was 46 % computer , 49 % clinician , 9 % relaxation at post-treatment ( week 10 ) and 58 % computer , 53 % clinician and -4 % relaxation at 1-month follow-up ( week 14 ) . Mean effect sizes on the primary outcome measures were 2.9 computer , 3.5 clinician and 0.5 relaxation at post-treatment ; and 3.7 computer , 3.5 clinician and 0.5 relaxation at 1-month follow-up . The assessor did not rate patients at follow-up . CONCLUSIONS Despite its ( non-significantly ) higher dropout rate , self-exposure therapy for panic/ phobia cut clinician time per patient by 73 % without losing efficacy when guided mainly by a computer rather than entirely by a clinician . The finding needs confirmation at a follow-up that is longer and includes a blind assessor . Self-relaxation had the highest rate of completers but was ineffective Background Generalised anxiety disorder ( GAD ) is a high prevalence , chronic psychiatric disorder which commonly presents early in the lifespan . Internet e-health applications have been found to be successful in reducing symptoms of anxiety and stress for post traumatic stress disorder ( PTSD ) , panic disorder , social phobia and depression . However , to date , there is little evidence for the effectiveness of e-health applications in adult GAD . There are no studies which have directly compared e-health applications with recognised evidence -based medication . This study aims to determine the effectiveness of a web-based program for treating GAD relative to sertraline and attention placebo . Methods / Design 120 community-dwelling participants , aged 18 - 30 years with a clinical diagnosis of GAD will be recruited from the Australian Electoral Roll . They will be r and omly allocated to one of three conditions : ( i ) an online treatment program for GAD , E-couch ( ii ) pharmacological treatment with a selective serotonin re-uptake inhibitor ( SSRI ) , sertraline ( a fixed-flexible dose of 25 - 100 mg/day ) or ( iii ) an attention control placebo , HealthWatch . The treatment program will be completed over a 10 week period with a 12 month follow-up . Discussion As of February 2010 , there were no registered trials evaluating the effectiveness of an e-health application for GAD for young adults . Similarly to date , this will be the first trial to compare an e-health intervention with a pharmacological treatment . Trial Registration Current Controlled Trials IS RCT Fifty-five people with panic disorder ( PD ) were r and omised to internet-based cognitive behavioural panic treatment ( CBT ) ( with email contact ) , therapist-assisted CBT manual or information-only control ( both with telephone contact ) . Both CBT treatments were more effective in reducing PD symptomatology , panic-related cognition , negative affect , and number of GP visits and improving physical health ratings . Internet treatment was more effective than CBT manual in reducing clinician-rated agoraphobia and number of GP visits at post- assessment . At follow-up , these effects were maintained for both CBT groups , with internet CBT better at improving physical health ratings and reducing GP visits . This study provides support for the efficacy of internet-based CBT This study offers data about the efficacy of " Talk to Me , " an Internet-based telepsychology program for the treatment of fear of public speaking that includes the most active components in cognitive-behavior therapy ( CBT ) for social phobia ( exposure and cognitive therapies ) . One hundred twenty-seven participants with social phobia were r and omly assigned to three experimental conditions : ( a ) an Internet-based self-administered program ; ( b ) the same program applied by a therapist ; ( c ) a waiting-list control group . Results showed that both treatment conditions were equally efficacious . In addition , Talk to Me and the same treatment applied by a therapist were more efficacious than the waiting-list condition . Treatment gains were maintained at 1-year follow-up . The results from this study support the utility of Internet-delivered CBT programs in order to reach a higher number of people who could benefit from CBT . Internet-delivered CBT programs could also play a valuable role in the dissemination of CBT Objective : In two r and omized controlled trials Titov et al. demonstrated significant benefit from an Internet- and email-based treatment programme for social phobia : the Shyness programme . Data are presented about the longer term outcomes ( 6 months after treatment ) , cost-effectiveness relative to face-to-face treatment , and the acceptability of the programme to participants . Method : Participants completed outcome and acceptability question naires at 6 months after treatment . Repeated measures analyses of variance were calculated using an intention-to-treat design . Cost-effectiveness in years lived with disability averted were calculated based on between-group effect sizes . Results : A total of 59 % of treatment group participants completed the 6 month follow-up question naires . Between post-treatment and 6 month follow up participants continued to make improvements in symptoms of social phobia , while maintaining improvements in mood , psychological distress , and disability . At 6 month follow up the mean within-group effect size ( Cohen 's d ) for the two social phobia measures increased from 1.2 to 1.4 . Cost-effectiveness in years lived with disability ( YLD ) averted was calculated as one-quarter that of face-to-face group treatment , or $ AUD1495 for one YLD gained , compared to $ AUD5686/YLD gained . Participants rated the Internet treatment to be as effective and helpful as face-to-face treatment . Conclusions : The present results confirm the reliability of the short-term findings reported in the first two Shyness programmes . The procedure appears to be very cost-effective , and acceptable to participants . These data provide further support for the development of Internet-based virtual clinics for common mental disorders UNLABELLED Self-help and psychoeducation have been identified as effective methods for delivering treatment , yet not everyone benefits from these brief interventions . Therefore it is clinical ly and economically useful to identify who is likely to require more intensive assistance . This paper develops a prognostic scale which predicts who will recover from panic attacks and who will require more assistance . METHOD R and om regression models were used to evaluate the relationship between predictive variables , baseline severity , and the rate of improvement in 117 people with DSMIV panic attacks who participated in a trial of a psycho-educational booklet , a self-help workbook , and brief group CBT over a 9-month period . ROC analysis was used to choose cut-off points on a scale made up of significant predictors . RESULTS Panic disorder and agoraphobia symptom measures were predicted by baseline social anxiety , and general mental health . There was no significant effect on the outcome for baseline depression or anxiety sensitivity . While general mental health ( SF12 Mental Component scores ) was predicted by the age at first panic attack , neuroticism , panic disorder and /or agoraphobia symptoms and a positive screen for alcohol use disorders . A prognostic scale based on simple additive scoring was equivalent to st and ard scores and significantly better than chance at predicting who would recover and who required face-to-face therapy . CONCLUSIONS The prognostic scale may be used to guide the choice of psychoeducation , self-help or face-to-face therapy as the first step in stepped care OBJECTIVE Research has consistently shown that highly anxious individuals tend to show an attentional bias in favor of threat cues ( i.e. , a threat bias ) . Further , recent evidence suggests that it is possible to modify patterns of attention allocation for such stimuli and the result ing changes in attention allocation alter affective responses to stress . However , to date such changes in patterns of attention have been shown only over brief time intervals and only in non-anxious individuals who lack a pre-existing attentional bias . In contrast , the present study tested the efficacy of such attentional training in a sample of severe worriers over an extended period of time using psychometrically vali date d measures of anxiety and depression . METHOD Twenty-four adult participants reporting severe worry were r and omly assigned to receive five sessions of either computer-delivered attentional retraining or sham training . The study was conducted from January to August 2001 and June to August 2002 . RESULTS Significant Treatment Group X Time interactions were found for both threat bias ( p=001 ) and a composite measure of anxious and depressive symptoms ( p=.002 ) . Compared to sham-training , the active retraining program produced significant reductions in both threat bias and symptoms . CONCLUSIONS These data support the view that an attentional bias in favor of threat cues is an important causal factor in generalized anxiety and suggest that a computer-based attentional retraining procedure may be an effective component of treatment Clinician-guided Internet-based cognitive behavioural therapy ( iCBT ) programs are clinical ly effective at treating specific anxiety disorders . The present study examined the efficacy of a transdiagnostic Internet-based cognitive behavioural treatment ( iCBT ) program to treat more than one anxiety disorder within the same program ( the Anxiety Program ) . Eighty six individuals meeting diagnostic criteria for generalized anxiety disorder ( GAD ) , panic disorder , and /or social phobia were r and omly assigned to a treatment group , or to a waitlist control group . Treatment consisted of CBT based online educational lessons and homework assignments , weekly email or telephone contact from a clinical psychologist , access to a moderated online discussion forum , and automated emails . An intention-to-treat model using the baseline-observation-carried-forward principle was employed for data analyses . Seventy-five percent of treatment group participants completed all 6 lessons within the 8 week program . Post-treatment data was collected from 38/40 treatment group and 38/38 control group participants , and 3-month follow-up data was collected from 32/40 treatment group participants . Relative to controls , treatment group participants reported significantly reduced symptoms of anxiety as measured by the Generalized Anxiety Disorder - 7 Item , Social Phobia Screening Question naire , and the Panic Disorder Severity Rating Scale - Self Report Scale , but not on the Penn State Worry Question naire , with corresponding between-groups effect sizes ( Cohen 's d ) at post-treatment of 0.78 , 0.43 , 0.43 , and 0.20 , respectively . The clinician spent a total mean time of 46min per person over the program , participants rated the procedure as moderately acceptable , and gains were sustained at follow-up . Modifications to the Anxiety program , based on post-treatment feedback from treatment group participants , were associated with improved outcomes in the control group . These results indicate that transdiagnostic programs for anxiety disorders may be successfully administered via the Internet BACKGROUND The dem and for effective behavior therapy for obsessive-compulsive disorder ( OCD ) by exposure and ritual prevention exceeds its supply by trained therapists . A computer-guided behavior therapy self-help system ( BT STEPS ) was created that patients access by telephone from home via interactive voice response technology . This study compared the value of computer-guided behavior therapy value with that of clinician-guided behavior therapy and systematic relaxation as a control treatment . METHOD After screening by a clinician , 218 patients with DSM-IV OCD at 8 North American sites were r and omly assigned to 10 weeks of behavior therapy treatment guided by ( 1 ) a computer accessed by telephone and a user workbook ( N = 74 ) or ( 2 ) a behavior therapist ( N = 69 ) or ( 3 ) systematic relaxation guided by an audiotape and manual ( N = 75 ) . RESULTS By week 10 , in an intent-to-treat analysis , mean change in score on the Yale-Brown Obsessive Compulsive Scale was significantly greater in clinician-guided behavior therapy ( 8.0 ) than in computer-guided ( 5.6 ) , and changes in scores with both clinician-guided and computer-guided behavior therapy were significantly greater than with relaxation ( 1.7 ) , which was ineffective . Similarly , the percentage of responders on the Clinical Global Impressions scale was significantly ( p < .05 ) greater with clinician-guided ( 60 % ) than computer-guided behavior therapy ( 38 % ) , and both were significantly greater than with relaxation ( 14 % ) . Clinician-guided was superior to computer-guided behavior therapy overall , but not when patients completed at least 1 self-exposure session ( N = 36 [ 65 % ] ) . At endpoint , patients were more satisfied with either behavior therapy group than with relaxation . Patients assigned to computer-guided behavior therapy improved more the longer they spent telephoning the computer ( mostly outside usual office hours ) and doing self-exposure . They improved slightly further by week 26 follow-up , unlike the other 2 groups . CONCLUSION For OCD , computer-guided behavior therapy was effective , although clinician-guided behavior therapy was even more effective . Systematic relaxation was ineffective . Computer-guided behavior therapy can be a helpful first step in treating patients with OCD when clinician-guided behavior therapy is unavailable Background Mood and anxiety disorders are highly prevalent and have a large impact on the lives of the affected individuals . Therefore , optimal treatment of these disorders is highly important . In this study we will examine the effectiveness of a stepped care program for primary care patients with mood and anxiety disorders . A stepped care program is characterized by different treatment steps that are arranged in order of increasing intensity . Methods This study is a r and omised controlled trial with two conditions : stepped care and care as usual , whereby the latter forms the control group . The stepped care program consists of four evidence based interventions : ( 1 ) Watchful waiting , ( 2 ) Guided self-help , ( 3 ) Problem Solving Treatment and ( 4 ) Medication and /or specialized mental health care . The study population consists of primary care attendees aged 18–65 years . Screeners are sent to all patients of the participating general practitioners . Individuals with a Diagnostic and Statistical Manual of mental disorders ( DSM ) diagnosis of major depression , dysthymia , panic disorder ( with or without agoraphobia ) , generalized anxiety disorder , or social phobia are included as well as individuals with minor depression and anxiety disorders . Primary focus is the reduction of depressive and anxiety symptoms . Both conditions are monitored at 8 , 16 and 24 weeks . Discussion This study evaluates the effectiveness of a stepped care program for patients with depressive and anxiety disorder . If effective , a stepped care program can form a worthwhile alternative for care as usual . Strengths and limitations of this study are discussed . Trial Registration Current Controlled Trails : IS RCT N17831610 Background Internet-administered cognitive behavioural therapy ( ICBT ) has been found to be effective for a range of anxiety disorders . However , most studies have focused on one specific primary diagnosis and co-morbidity has not been considered . In primary care setting s , patients with anxiety often suffer from more than one psychiatric condition , making it difficult to disseminate ICBT for specific conditions . The aim of this study will be to investigate if ICBT tailored according to symptom profile can be a feasible treatment for primary care patients with anxiety disorders . It is a r and omised controlled trial aim ed to evaluate the treatment against an active control group . Methods Participants with anxiety disorders and co-morbid conditions ( N = 128 ) , will be recruited from a primary care population . The Clinical Outcome in Routine Evaluation ( CORE-OM ) will serve as the primary outcome measure . Secondary measures include self-reported depression , anxiety , quality of life and loss of production and the use of health care . All assessment s will be collected via the Internet and measure points will be baseline , post treatment and 12 months post treatment . Discussion This trial will add to the body of knowledge on the effectiveness of ICBT for anxiety disorders in primary care . The trial will also add knowledge on the long term effects of ICBT when delivered for regular clinic patients Trial Registration Clinical Trials.gov : Abstract The present study was an attempt to compare the efficacy of three treatments in reducing the fear of a harmless snake , to determine whether extraverts and introverts are differentially affected by systematic desensitization and to determine whether scores on an anxiety test are reduced as a result of successful treatment of a specific fear . Twenty-nine snake-fearing college students were r and omly divided into three groups . A systematic desensitization group was treated in the usual manner , whereas a programmed fantasy group imagined the same scenes for the same length of time as the systematic desensitization group , but had no instructions in relaxation and had minimal contact with E. A bibliotherapy group read about snakes , and also had minimal contact with E. No significant differences were found between the efficacy of systematic desensitization and programmed fantasy , but both were more effective than bibliotherapy . These results were discussed in terms of the role of muscular relaxation in systematic desensitization . Systematic desensitization was found equally effective with extraverts , introverts and ambiverts , but successful treatment of the fear of a harmless snake did not result in a significant reduction of scores on an anxiety test Objective : Computerized cognitive behavioral therapy ( cCBT ) and cognitive bias modification for interpretation ( CBM-I ) both have demonstrated efficacy in alleviating social anxiety , but how they compare with each other has not been investigated . The present study tested the prediction that both interventions would reduce anxiety relative to a no-intervention comparison condition , but CBM-I would be particularly effective at modifying threat-related cognitive bias under high mental load . Method : Sixty-three primarily Caucasian adults ( mean age = 22.7 , SD = 5.87 ; 68.3 % female ) with high social anxiety , r and omly allocated to 3 groups : CBM-I ( n = 21 ) , cCBT ( n = 21 ) , and a no-intervention control group ( n = 21 ) provided complete data for analysis . Pre- and postintervention ( 4 sessions lasting 2 weeks , control participants only attended the pre – post sessions ) self-report measures of anxiety , depression , attentional control , and threat-related interpretive bias were completed . In addition , interpretive bias under high versus low cognitive load was measured using the Scrambled Sentences Test . Results : Both CBM-I and cCBT groups reported significantly reduced levels of social anxiety , trait anxiety , and depression and improved attentional control , relative to the control group , with no clear superiority of either active intervention . Although both active conditions reduced negative bias on the Scrambled Sentences Test completed under mental load , CBM-I was significantly more effective at doing so . Conclusions : The results suggest that although not differing in therapeutic efficacy , CBM-I and cCBT might differ in the resilience of their effects when under mental load Objective : To evaluate the effectiveness of a web-based multimedia health promotion program for the workplace , design ed to help reduce stress and to prevent depression , anxiety , and substance abuse . Methods : Using a r and omized controlled trial design , 309 working adults were r and omly assigned to the web-based condition or to a wait-list control condition . All participants were assessed on multiple self-reported outcomes at pretest and posttest . Results : Relative to controls , the web-based group reduced their stress , increased their knowledge of depression and anxiety , developed more positive attitudes toward treatment , and adopted a more healthy approach to alcohol consumption . Conclusions : We found that a brief and easily adaptable web-based stress management program can simultaneously reduce worker stress and address stigmatized behavioral health problems by embedding this prevention material into a more positive stress management framework Internet-based self-help for social phobia with minimal therapist support via email have shown efficacy in several controlled trials by independent research teams . The role and necessity of therapist guidance is , however , still largely unclear . The present study compared the benefits of a 10-week web-based unguided self-help treatment for social phobia with the same intervention complemented with minimal , although weekly , therapist support via email . Further , a third treatment arm was included , in which the level of support was flexibly stepped up , from no support to email or telephone contact , on dem and of the participants . Eighty-one individuals meeting diagnostic criteria for social phobia were r and omly assigned to one of the three conditions . Primary outcome measures were self-report measures of symptoms of social phobia . Secondary outcome measures included symptoms of depression , interpersonal problems , and general symptomatology . Measures were taken at baseline , post-treatment , and at 6-month follow-up . Data from a telephone-administered diagnostic interview conducted at post-treatment were also included . Results showed significant symptom reductions in all three treatment groups with large effect sizes for primary social phobia measures ( Cohen 's d=1.47 ) and for secondary outcome measures ( d=1.16 ) . No substantial and significant between-groups effects were found on any of the measures ( Cohen 's d=00-.36 ) . Moreover , no difference between the three conditions was found regarding diagnosis-free status , clinical ly significant change , dropout rates , or adherence measures such as lessons or exercises completed . These findings indicate that Internet-delivered treatment for social phobia is a promising treatment option , whether no support is provided or with two different types of therapist guidance Background Internet based self-help for panic disorder ( PD ) has proven to be effective . However , studies so far have focussed on treating a full-blown disorder . Panic symptoms that do not meet DSM-IV criteria are more prevalent than the full-blown disorder and patients with sub- clinical panic symptoms are at risk of developing PD . This study is a r and omised controlled trial aim ed to evaluate an Internet based self-help intervention for sub- clinical and mild PD compared to a waiting list control group . Methods Participants with mild or sub- clinical PD ( N = 128 ) will be recruited in the general population . Severity of panic and anxiety symptoms are the primary outcome measures . Secondary outcomes include depressive symptoms , quality of life , loss of production and health care consumption . Assessment s will take place on the Internet at baseline and three months after baseline . Discussion Results will indicate the effectiveness of Internet based self-help for sub- clinical and mild PD . Strengths of this design are the external validity and the fact that it is almost completely conducted online . Trial registration Netherl and s Trial Register ( NTR ) : NTR1639 The Netherl and s Trial Register is part of the Dutch Cochrane Centre Background Internet-based cognitive behavioural therapy ( iCBT ) for generalized anxiety disorder ( GAD ) has been shown to be effective when guided by a clinician . The present study sought to replicate this finding , and determine whether support from a technician is as effective as guidance from a clinician . Method R and omized controlled non-inferiority trial comparing three groups : Clinician-assisted vs. technician-assisted vs. delayed treatment . Community-based volunteers applied to the VirtualClinic ( www.virtualclinic.org.au ) research program and 150 participants with GAD were r and omized . Participants in the clinician- and technician-assisted groups received access to an iCBT program for GAD comprising six online lessons , weekly homework assignments , and weekly supportive contact over a treatment period of 10 weeks . Participants in the clinician-assisted group also received access to a moderated online discussion forum . The main outcome measures were the Penn State Worry Question naire ( PSWQ ) and the Generalized Anxiety Disorder-7 Item ( GAD-7 ) . Completion rates were high , and both treatment groups reduced scores on the PSWQ ( p<0.001 ) and GAD-7 ( p<0.001 ) compared to the delayed treatment group , but did not differ from each other . Within group effect sizes on the PSWQ were 1.16 and 1.07 for the clinician- and technician-assisted groups , respectively , and on the GAD-7 were 1.55 and 1.73 , respectively . At 3 month follow-up participants in both treatment groups had sustained the gains made at post-treatment . Participants in the clinician-assisted group had made further gains on the PSWQ . Approximately 81 minutes of clinician time and 75 minutes of technician time were required per participant during the 10 week treatment program . Conclusions Both clinician- and technician-assisted treatment result ed in large effect sizes and clinical ly significant improvements comparable to those associated with face-to-face treatment , while a delayed treatment/control group did not improve . These results provide support for large scale trials to determine the clinical effectiveness and acceptability of technician-assisted iCBT programs for GAD . This form of treatment has potential to increase the capacity of existing mental health services . Trial Registration Australian New Zeal and Clinical Trials Registry This study investigated 2 methods of disseminating a cognitive-behavioral intervention for panic disorder ( PD ) . Thirty-six Ss who met diagnostic criteria for PD according to the Anxiety Disorders Interview Schedule-Revised were r and omly assigned to 1 of 3 conditions : bibliotherapy ( BT ) , group therapy ( GT ) , or a waiting-list control ( WL ) condition . Interventions lasted 8 weeks and were followed by a posttest , along with 3- and 6-month follow-up assessment s. Results indicated that both the BT and GT treatments were more effective than the WL condition in reducing frequency of panic attacks , severity of physical panic symptoms , catastrophic cognitions , agoraphobic avoidance , and depression and that the BT and GT treatments were more effective in increasing self-efficacy . Both interventions maintained their effects throughout the follow-up periods and produced clinical ly significant levels of change among the majority of treated Ss Computer-based self-help treatments have been proposed to provide greater access to treatment while requiring minimum input from a therapist . The authors employed a r and omised controlled trial to investigate the efficacy of one-session computer-based exposure ( CBE ) as a self-help treatment for spider-fearful individuals . Spider-fearful participants in a CBE group underwent one 27-min session of st and ardised exposure to nine fear-eliciting spider pictures . Treatment outcome was compared to spider-fearful control participants exposed to nine neutral pictures . Fear reduction was quantified on a subjective level by the Fear of Spiders Question naire ( FSQ ) and complemented with a behavioural approach test ( BAT ) . Results demonstrate that compared to control participants , CBE participants showed greater fear reduction from pre- to posttreatment on both the subjective level ( FSQ ) and the behavioural level ( BAT ) . Moreover , in contrast to the control group , the obtained subjective fear reduction effect remained stable in the CBE group at 1-month follow-up . These findings highlight the role of computer-based self-help as a minimal but effective intervention to reduce fear of spiders Trichotillomania ( TTM ) is classified as an impulse control disorder characterized by the recurrent urge to pull out one 's own hair result ing in noticeable hair loss . Cognitive-behavioral therapy , involving habit reversal training , currently represents the treatment of choice . The present study assessed the feasibility and effectiveness of a novel self-help technique , entitled decoupling ( DC ) . DC aims at attenuating TTM by performing movements that decouple the behavioral elements involved in hair pulling . A total of 42 subjects with TTM were recruited via self-help forums for TTM and were r and omized either to DC or progressive muscle relaxation ( PMR ) . After four weeks , participants were asked to fill out the same question naires as before and rate the effectiveness of the intervention . The completion rate was high and the reliability of the assessment s at least satisfactory . The DC group showed a significantly greater decline on the Massachusetts General Hospital - Hair-Pulling Scale , which served as the primary outcome , relative to PMR indicating a medium to strong effect size . Declines on scales tapping depression and obsessive-compulsive disorder were comparable between the two groups . Despite some method ological limitations and the need for replication including follow-up and expert ratings , the present study suggests that DC may prove beneficial to a substantial number of individuals affected with TTM Cognitive behavioral bibliotherapy for panic disorder has been found to be less effective without therapist support . In this study , participants were r and omized to either unassisted bibliotherapy ( n=20 ) with a scheduled follow-up telephone interview or to a waiting list control group ( n=19 ) . Following a structured psychiatric interview , participants in the treatment group were sent a self-help book consisting of 10 chapters based on cognitive behavioral strategies for the treatment of panic disorder . No therapist contact of any kind was provided during the treatment phase , which lasted for 10 weeks . Results showed that the treatment group had , in comparison to the control group , improved on all outcome measures at posttreatment and at 3-month follow-up . The tentative conclusion drawn from these results is that pure bibliotherapy with a clear deadline can be effective for people suffering from panic disorder with or without agoraphobia Background Symptoms of depression and anxiety are highly prevalent in adolescence and they are the cause of considerable suffering . Even so , adolescents are not inclined to seek professional help for emotional problems . Internet-based preventive interventions have been suggested as a feasible method of providing appropriate care to adolescents with internalizing symptoms . The objective of this study was to evaluate the effects of preventive Internet-based ( guided ) self-help problem-solving therapy ( PST ) for adolescents reporting mild to moderate symptoms of depression and /or anxiety as compared to a waiting list control group ( WL ) . Methodology /Principal Findings A total of 45 participants were r and omized to the 2 conditions . PST consisted of 5 weekly lessons . Participants were supported by e-mail . Self-report measures of depression and anxiety were filled in at baseline and after 3 weeks , 5 weeks , and 4 months . Of the 45 participants , 28 ( 62.2 % ) completed question naires after 3 weeks , 28 ( 62.2 % ) after 5 weeks , and 27 ( 60 % ) after 4 months . Hierarchical linear modeling analyses revealed overall improvement over time for both groups on depressive and anxiety symptoms . However , no significant group x time interactions were found . No differences were found between completers and non-completers . Conclusions / Significance Results show that depressive and anxiety symptoms declined in both groups . No support was found , however , for the assumption that Internet-based PST was efficacious in reducing depression and anxiety in comparison to the waiting list control group . This finding could represent lack of power . Trial Registration Netherl and s Trial Register Background Internet administered cognitive behaviour therapy ( CBT ) is a promising new way to deliver psychological treatment , but its effectiveness in regular care setting s and in relation to more traditional CBT group treatment has not yet been determined . The primary aim of this study was to compare the effectiveness of Internet- and group administered CBT for panic disorder ( with or without agoraphobia ) in a r and omised trial within a regular psychiatric care setting . The second aim of the study was to establish the cost-effectiveness of these interventions . Methods Patients referred for treatment by their physician , or self-referred , were telephone-screened by a psychiatric nurse . Patients fulfilling screening criteria underwent an in-person structured clinical interview carried out by a psychiatrist . A total of 113 consecutive patients were then r and omly assigned to 10 weeks of either guided Internet delivered CBT ( n = 53 ) or group CBT ( n = 60 ) . After treatment , and at a 6-month follow-up , patients were again assessed by the psychiatrist , blind to treatment condition . Results Immediately after r and omization 9 patients dropped out , leaving 104 patients who started treatment . Patients in both treatment conditions showed significant improvement on the main outcome measure , the Panic Disorder Severity Scale ( PDSS ) after treatment . For the Internet treatment the within-group effect size ( pre-post ) on the PDSS was Cohen 's d = 1.73 , and for the group treatment it was d = 1.63 . Between group effect sizes were low and treatment effects were maintained at 6-months follow-up . We found no statistically significant differences between the two treatment conditions using a mixed models approach to account for missing data . Group CBT utilised considerably more therapist time than did Internet CBT . Defining effect as proportion of PDSS responders , the cost-effectiveness analysis concerning therapist time showed that Internet treatment had superior cost-effectiveness ratios in relation to group treatment both at post-treatment and follow-up . Conclusions This study provides support for the effectiveness of Internet CBT in a psychiatric setting for patients with panic disorder , and suggests that it is equally effective as the more widely used group administered CBT in reducing panic- and agoraphobic symptoms , as well as being more cost effective with respect to therapist time . Trial registration Clinical Trials.gov Background Internet-based self-help is an effective preventive intervention for highly prevalent disorders , such as depression and anxiety . It is not clear , however , whether it is necessary to offer these interventions with professional support or if they work without any guidance . In case support is necessary , it is not clear which level of support is needed . This study examines whether an internet-based self-help intervention with a coach is more effective than the same intervention without a coach in terms of clinical outcomes , drop-out and economic costs . Moreover , we will investigate which level of support by a coach is more effective compared to other levels of support . Methods In this r and omized controlled trial , a total of 500 subjects ( 18 year and older ) from the general population with mild to moderate depression and /or anxiety will be assigned to one of five conditions : ( 1 ) web-based problem solving through the internet ( self-examination therapy ) without a coach ; ( 2 ) the same as 1 , but with the possibility to ask help from a coach on the initiative of the respondent ( on dem and , by email ) ; ( 3 ) the same as 1 , but with weekly scheduled contacts initiated by a coach ( once per week , by email ) ; ( 4 ) weekly scheduled contacts initiated by a coach , but no web-based intervention ; ( 5 ) information only ( through the internet ) . The interventions will consist of five weekly lessons . Primary outcome measures are symptoms of depression and anxiety . Secondary outcome measures are drop-out from the intervention , quality of life , and economic costs . Other secondary outcome measures that may predict outcome are also studied , e.g. client satisfaction and problem-solving skills . Measures are taken at baseline ( pre-test ) , directly after the intervention ( post-test , five weeks after baseline ) , 3 months later , and 12 months later . Analysis will be conducted on the intention-to-treat sample . Discussion This study aims to provide more insight into the clinical effectiveness , differences in drop-out rate and costs between interventions with and without support , and in particular different levels of support . This is important to know in relation to the dissemination of internet-based self-help interventions .Trial Registration Nederl and s Trial Register ( NTR ) : Background : R and omized controlled trials have established that individual cognitive therapy based on the Clark and Wells ( 1995 ) model is an effective treatment for social anxiety disorder that is superior to a range of alternative psychological and pharmacological interventions . Normally the treatment involves up to 14 weekly face-to-face therapy sessions . Aim : To develop an internet based version of the treatment that requires less therapist time . Method : An internet-delivered version of cognitive therapy ( iCT ) for social anxiety disorder is described . The internet-version implements all key features of the face-to-face treatment ; including video feedback , attention training , behavioural experiments , and memory focused techniques . Therapist support is via a built-in secure messaging system and by brief telephone calls . A cohort of 11 patients meeting DSM-IV criteria for social anxiety disorder worked through the programme and were assessed at pretreatment and posttreatment . Results : No patients dropped out . Improvements in social anxiety and related process variables were within the range of those observed in r and omized controlled trials of face-to-face CT . Nine patients ( 82 % ) were classified as treatment responders and seven ( 64 % ) achieved remission status . Therapist time per patient was only 20 % of that in face-to-face CT . Conclusions : iCT shows promise as a way of reducing therapist time without compromising efficacy . Further evaluation of iCT is ongoing Background Guided internet-delivered cognitive behavior therapy ( ICBT ) has been tested in several trials on social anxiety disorder ( SAD ) with moderate to large effects . The aims of this study were threefold . First , to compare the effects of ICBT including online discussion forum with a moderated online discussion forum only . Second , to investigate if knowledge about SAD increased following treatment and third to compare the effects of inexperienced versus experienced therapists on patient outcomes . Methods A total of 204 participants with a primary diagnosis of SAD were included and r and omized to either guided ICBT or the control condition . ICBT consisted of a 9-week treatment program which was guided by either psychology students at MSc level ( n = 6 ) or by licensed psychologists with previous experience of ICBT ( n = 7 ) . A knowledge test dealing with social anxiety was administered before and after treatment . Measures of social anxiety and secondary outcomes dealing with general anxiety , depression , and quality of life were administered before and after treatment . In addition , a 1-year follow-up was conducted on the treated individuals . Results Immediately following treatment , the ICBT group showed superior outcome on the Liebowitz Social Anxiety Scale self-report version with a between group posttreatment Hedges g effect size of g = 0.75 . In addition , significant differences on all the secondary outcomes were observed . Gains were well maintained one year later . Knowledge , as assessed by the knowledge test , increased following treatment with little gain in the control group . Therapist experience did not result in different outcomes , but experienced therapists logged in less frequently compared to the inexperienced therapists , suggesting that they needed less time to support patients . Discussion We conclude that guided ICBT reduce symptoms of SAD , increase knowledge about SAD and that therapist experience does not make a difference apart from the finding that experienced therapist may require less time to guide patients . Trial Registration UMIN.ac.jp The present study examined a relapse prevention ( RP ) program delivered via bibliotherapy in the treatment of individuals with panic attacks . Compared with a wait list control group , individuals receiving RP exhibited significant reductions on measures of frequency of panic attacks , panic cognitions , anticipatory anxiety , avoidance , and depression . In addition , individuals in the RP group were more likely to attain a " clinical ly significant change " in status on both panic-free status and level of avoidance more frequently than individuals in the control group . When compared with treatment effects evaluated in two prior phases of the study , the obtained results appear to be the product of a synchronous effect of bibliotherapy and minimal phone contact during the 6-month follow-up period . The results reflect the importance of brief therapist contact in increasing motivation for active participation in bibliotherapy interventions This study compared Panic Online ( PO ) , an internet-based CBT intervention , to best- practice face-to-face CBT for people with panic disorder with or without agoraphobia . Eighty-six people with a primary diagnosis of panic disorder were recruited from Victoria , Australia . Participants were r and omly assigned to either PO ( n=46 ) or best practice face-to-face CBT ( n=40 ) . Effects of the internet-based CBT program were found to be comparable to those of face-to-face CBT . Both interventions produced significant reductions in panic disorder and agoraphobia clinician severity ratings , self reported panic disorder severity and panic attack frequency , measures of depression , anxiety , stress and panic related cognitions , and displayed improvements in quality of life . Participants rated both treatment conditions as equally credible and satisfying . Participants in the face-to-face CBT treatment group cited higher enjoyment with communicating with their therapist . Consistent with this , therapists ' ratings for compliance to treatment and underst and ing of the CBT material was higher in the face-to-face CBT treatment group . PO required significantly less therapist time than the face-to-face CBT condition OBJECTIVE This study examined the feasibility , acceptability , and effects of Camp Cope-A-Lot ( CCAL ) , a computer-assisted cognitive behavioral therapy ( CBT ) for anxiety in youth . METHOD Children ( 49 ; 33 males ) ages 7 - 13 ( M = 10.1 ± 1.6 ; 83.7 % Caucasian , 14.2 % African American , 2 % Hispanic ) with a principal anxiety disorder were r and omly assigned to ( a ) CCAL , ( b ) individual CBT ( ICBT ) , or ( c ) a computer-assisted education , support , and attention ( CESA ) condition . All therapists were from the community ( school or counseling psychologists , clinical psychologist ) or were PsyD or PhD trainees with no experience or training in CBT for child anxiety . Independent diagnostic interviews and self-report measures were completed at pre- and posttreatment and 3-month follow-up . RESULTS At posttreatment , ICBT or CCAL children showed significantly better gains than CESA children ; 70 % , 81 % , and 19 % , respectively , no longer met criteria for their principal anxiety diagnosis . Gains were maintained at follow-up , with no significant differences between ICBT and CCAL . Parents and children rated all treatments acceptable , with CCAL and ICBT children rating higher satisfaction than CESA children . CONCLUSIONS Findings support the feasibility , acceptability and beneficial effects of CCAL for anxious youth . Discussion considers the potential of computer-assisted treatments in the dissemination of empirically supported treatments Background Anxiety disorders share common vulnerabilities and symptoms . Disorder-specific treatment is efficacious , but few access evidence -based care . Administering transdiagnostic cognitive-behavioral therapy via the internet ( iCBT ) may increase access to evidence -based treatment , with a recent r and omized controlled trial ( RCT ) providing preliminary support for this approach . This study extends those findings and aims to answer three questions : Is a transdiagnostic iCBT program for anxiety disorders efficacious and acceptable ? Does it result in change for specific disorders ? Can good clinical outcomes be obtained when guidance is provided via a Coach rather than a Clinician ? Method RCT ( N = 131 ) comparing three groups : Clinician-supported ( CL ) vs. Coach-supported ( CO ) vs. waitlist control ( Control ) . Individuals met DSM-IV criteria for a principal diagnosis of generalized anxiety disorder ( GAD ) , social phobia ( SP ) or panic disorder with or without agoraphobia ( Pan/Ag ) . Treatment consisted of an 8-lesson/10 week iCBT program with weekly contact from a Clinician or Coach , and follow-up at 3-months post-treatment . Results Outcomes for the pooled treatment groups ( CL+CO ) were superior to the Control group on measures of anxiety , depression and disability , were associated with medium to large effect sizes ( Cohen 's d = .76 – 1.44 ) ( response rate = 89–100 % ) , and were maintained at follow-up . Significant reductions were found on disorder-specific outcomes for each of the target diagnoses , and were associated with large effect sizes . CO participants achieved similar outcomes to CL participants at post-treatment , yet had significantly lower symptom severity scores on general anxiety , panic-disorder , depression and disability at follow-up ( d = .45 – .46 ) . Seventy-four percent of CO and 76 % of CL participants completed the program . Less than 70 minutes of Clinician or Coach time was required per participant during the program . Discussion This transdiagnostic iCBT course for anxiety appears to be efficacious , associated with significant change for three target disorders , and is efficacious when guided by either a Clinician or Coach . Trial Registration Australian New Zeal and Clinical Trials Registry Background : Settling and night waking problems are particularly prevalent , persistent , and generally considered difficult to treat in children with a learning disability , although intervention trials are few . Scarce re sources , however , limit access to proven behavioural treatments . Aims : To investigate the efficacy of a media based brief behavioural treatment of sleep problems in such children by comparing ( 1 ) face-to-face delivered treatment versus control and ( 2 ) booklet delivered treatment versus controls . Methods : The parents of 66 severely learning disabled children aged 2–8 years with settling and /or night waking problems took part in a r and omised controlled trial with a wait-list control group . Behavioural treatments were presented either conventionally face-to-face or by means of a 14 page easy to read illustrated booklet . A composite sleep disturbance score was derived from sleep diaries kept by parents . Results : Both forms of treatment were almost equally effective compared with controls . Two thirds of children who were taking over 30 minutes to settle five or more times per week and waking at night for over 30 minutes four or more times per week improved on average to having such settling or night waking problems for only a few minutes or only once or twice per week ( H = 34.174 , df = 2 , p<0.001 ) . These improvements were maintained after six months . Conclusions : Booklet delivered behavioural treatments for sleep problems were as effective as face-to-face treatment for most children in this population Background The aim of the present study was to assess possible effects on mental and physical well-being and stress-related biological markers of a web-based health promotion tool . Methods A r and omized , prospect ively controlled study was conducted with before and after measurements , involving 303 employees ( 187 men and 116 women , age 23–64 ) from four information technology and two media companies . Half of the participants were offered web-based health promotion and stress management training ( intervention ) lasting for six months . All other participants constituted the reference group . Different biological markers were measured to detect possible physiological changes . Results After six months the intervention group had improved statistically significantly compared to the reference group on ratings of ability to manage stress , sleep quality , mental energy , concentration ability and social support . The anabolic hormone dehydroepi and osterone sulphate ( DHEA-S ) decreased significantly in the reference group as compared to unchanged levels in the intervention group . Neuropeptide Y ( NPY ) increased significantly in the intervention group compared to the reference group . Chromogranin A ( CgA ) decreased significantly in the intervention group as compared to the reference group . Tumour necrosis factor α ( TNFα ) decreased significantly in the reference group compared to the intervention group . Logistic regression analysis revealed that group ( intervention vs. reference ) remained a significant factor in five out of nine predictive models . Conclusion The results indicate that an automatic web-based system might have short-term beneficial physiological and psychological effects and thus might be an opportunity in counteracting some clinical ly relevant and common stress and health issues of today Background Cognitive behaviour therapy ( CBT ) is an effective treatment for obsessive – compulsive disorder ( OCD ) but access to CBT is limited . Internet-based CBT ( ICBT ) with therapist support is potentially a more accessible treatment . There are no r and omized controlled trials testing ICBT for OCD . The aim of this study was to investigate the efficacy of ICBT for OCD in a r and omized controlled trial . Method Participants ( n=101 ) diagnosed with OCD were r and omized to either 10 weeks of ICBT or to an attention control condition , consisting of online supportive therapy . The primary outcome measure was the Yale – Brown Obsessive Compulsive Scale ( YBOCS ) administered by blinded assessors . Results Both treatments lead to significant improvements in OCD symptoms , but ICBT result ed in larger improvements than the control condition on the YBOCS , with a significant between-group effect size ( Cohen 's d ) of 1.12 ( 95 % CI 0.69–1.53 ) at post-treatment . The proportion of participants showing clinical ly significant improvement was 60 % ( 95 % CI 46–72 ) in the ICBT group compared to 6 % ( 95 % CI 1–17 ) in the control condition . The results were sustained at follow-up . Conclusions ICBT is an efficacious treatment for OCD that could substantially increase access to CBT for OCD patients . Replication studies are warranted Introduction Cognitive behaviour therapy delivered in the format of guided self-help via the internet has been found to be effective for a range of conditions , including depression and anxiety disorders . Recent results indicate that guided self-help via the internet is a promising treatment format also for psychodynamic therapy . However , to date and to our knowledge , no study has evaluated internet-delivered psychodynamic therapy as a transdiagnostic treatment . The affect-phobia model of psychopathology by McCullough et al provides a psychodynamic conceptualisation of a range of psychiatric disorders . The aim of this study will be to test the effects of a transdiagnostic guided self-help treatment based on the affect-phobia model in a sample of clients with depression and anxiety . Methods and analysis This study will be a r and omised controlled trial with a total sample size of 100 participants . The treatment group receives a 10-week , psychodynamic , guided self-help treatment based on the transdiagnostic affect-phobia model of psychopathology . The treatment consists of eight text-based treatment modules and includes therapist contact in a secure online environment . Participants in the control group receive similar online therapist support without any treatment modules . Outcome measures are the 9-item Patient Health Question naire Depression Scale and the 7-item Generalised Anxiety Disorder Scale ( GAD-7 ) . Process measures that concerns emotional processing and mindfulness are included . All outcome and process measures will be administered weekly via the internet and at 6-month follow-up . Discussion This trial will add to the body of knowledge on internet-delivered psychological treatments in general and to psychodynamic treatments in particular . We also hope to provide new insights in the effectiveness and working mechanisms of psychodynamic therapy based on the affect-phobia model BACKGROUND The clinical Global Impression Scale ( CGI ) is commonly used as a primary outcome measure in studies evaluating the efficacy of treatments for anxiety disorders . The current study evaluated the psychometric properties and predictors of clinicians ' ratings on an adapted version of the CGI among individuals with social anxiety disorders . METHOD An independent assessor administered the CGI Severity of Illness and Improvement ratings to 123 patients at baseline and the subset of treated patients again mid- and post-treatment . RESULTS Improvement ratings were strongly related to both concurrent Severity of Illness and changes in Severity of Illness ratings from baseline . Additionally , both CGI ratings were positively correlated with both self-report and clinician-administered measures of social anxiety , depression , impairment and quality of life . Measures of social anxiety symptoms accounted for a large portion of the variance in Severity of Illness ratings , with significant additional variance accounted for by measures of impairment and depression . Changes in social anxiety symptoms from baseline accounted for significant variance in Improvement ratings , but no significant additional variance was accounted for by changes in impairment and depressive symptoms . CONCLUSIONS Our findings support the utility of the CGI as an index of global severity and symptom-specific improvement among individuals with social anxiety disorder Background Due to language limitations , the abstract of journal article may be the only way for people of non-Chinese speaking countries to know about trials in traditional Chinese medicine ( TCM ) . However , little is known about the reporting quality of these trial abstract s. Our study is to assess the reporting quality of abstract s of r and omized controlled trials ( RCT ) published in four leading Chinese medical journals of TCM , and to identify any differences in reporting between the Chinese and English version of the same abstract publication . Method Two review ers h and - search ed the Chinese Journal of Integrated Traditional and Western Medicine , the Chinese Journal of Integrative Medicine , the China Journal of Chinese Materia Medica and the Chinese Acupuncture & Moxibustion for all abstract s of RCTs published between 2006 and 2007 . Two review ers independently assessed the reporting quality of the Chinese and English version of all eligible abstract s based on a modified version of the CONSORT for reporting r and omised trials in journal and conference abstract s ( CONSORT for abstract s ) . Results We identified a total of 345 RCTs of TCM with both a Chinese and English abstract . More than half of Chinese abstract s reported details of the trial participants ( 68 % ; 234/345 ) , control group intervention ( 52 % ; 179/345 ) , the number of participants r and omized ( 73 % ; 253/345 ) and benefits when interpreting the trial results ( 55 % ; 190/345 ) . Reporting of method ological quality or key features of trial design and trial results were poor ; only 2 % ( 7/345 ) included details of the trial design , 3 % ( 11/345 ) defined the primary outcome , 5 % ( 17/345 ) described the methods of r and om sequence generation , and only 4 % ( 13/345 ) reported the number of participants analyzed . No abstract s provided details on allocation concealment and trial registration . The percentage agreement in reporting ( between the Chinese and English version of the same abstract ) ranged from 84 % to 100 % across individual checklist item . Conclusion The reporting quality of abstract s of RCTs published in these four TCM journals needs to be improved . Since none of the four journals adopted CONSORT for Abstract s , we hope that the introduction and adoption of CONSORT for Abstract s by TCM journals will lead to an improvement in reporting quality Social anxiety is a common mental disorder among adolescents and is associated with detrimental long term outcomes . Therefore , this study investigated the efficacy of two possible early interventions for adolescent social anxiety and test anxiety . An internet-based cognitive bias modification ( CBM ; n = 86 ) was compared to a school-based cognitive behavioral group training ( CBT ; n = 84 ) and a control group ( n = 70 ) in reducing symptoms of social and test anxiety in high socially and /or test anxious adolescents aged 13–15 years . Participants ( n = 240 ) were r and omized at school level over the three conditions . CBM consisted of a 20-session at home internet-delivered training ; CBT was a 10-session at school group training with homework assignments ; the control group received no training . Participants were assessed before and after the intervention and at 6 and 12 month follow-up . At 6 month follow-up CBT result ed in lower social anxiety than the control condition , while for CBM , this effect was only trend-significant . At 12 month follow-up this initial benefit was no longer present . Test anxiety decreased more in the CBT condition relative to the control condition in both short and long term . Interestingly , in the long term , participants in the CBM condition improved more with regard to automatic threat-related associations than both other conditions . The results indicate that the interventions result ed in a faster decline of social anxiety symptoms , whereas the eventual end point of social anxiety was not affected . Test anxiety was influenced in the long term by the CBT intervention , and CBM lead to increased positive automatic threat-related associations . Trial Registration TrialRegister.nl BACKGROUND Self-help for social phobia has not received controlled empirical evaluation . AIMS To evaluate the efficacy of pure self-help through written material s for severe social phobia and self-help augmented by five group sessions with a therapist . These conditions were compared with a waiting-list control and st and ard , therapist-led group therapy . METHOD Participants with severe generalised social phobia ( n=224 ) were r and omised to one of four conditions . Assessment included diagnoses , symptoms and life interference at pretreatment , 12 weeks and at 24 weeks . RESULTS A larger percentage of patients no longer had a diagnosis of social phobia at post-intervention in the pure self-help group than in the waiting-list group , although this percentage decreased slightly over the next 3 months . Symptoms of social anxiety and life interference did not differ significantly between these groups . Augmented self-help was better than waiting list on all measures and did not differ significantly from group treatment . CONCLUSIONS Self-help augmented by therapist assistance shows promise as a less re source -intensive method for the management of social phobia . Pure self-help shows limited efficacy for this disorder The purpose of this study was to examine the relationship between change in anxiety sensitivity , as measured by the Anxiety Sensitivity Index ( ASI ) , and treatment outcome in a sample of 106 subjects with a DSM-III-R diagnosis of panic disorder ( with or without agoraphobia ) who were participants in an evaluation study of cognitive-behavioral treatment . Results revealed that subjects who received active treatment had significantly lower anxiety sensitivity scores at post-treatment than the wait-list control group . We also examined change in anxiety sensitivity from pre- to post-treatment in reference to Clinical Global Improvement ( CGI ) ratings and with the effect size statistic . Subjects who showed improvement based on CGI ratings also demonstrated a reduction in anxiety sensitivity . Furthermore , the effect sizes obtained with the ASI were greater in magnitude than those obtained with other widely used anxiety self-report measures . Taken together , the finds supported the use of the Anxiety Sensitivity Index as a treatment outcome measure in panic disorder research BACKGROUND Common mental health problems account for up to 40 % of all general practitioner ( GP ) consultations . Patients have limited access to evidence -based psychological therapies . Cognitive behavioural therapy self-help strategies offer one potential solution . AIM To determine differences in clinical outcome , patient satisfaction and costs , between a cognitive behavioural-based self-help package facilitated by practice nurses compared to ordinary care by GPs for mild to moderate anxiety and depression . DESIGN OF STUDY R and omised controlled trial . SETTING Seventeen primary healthcare teams . METHOD Patients presenting to their GP with mild to moderate anxiety and /or depression were recruited to the study and r and omised to receive either a self-help intervention facilitated by practice nurses or ordinary care . The self-help intervention consisted of up to three appointments : two 1 week apart and a third 3 months later . There were no restrictions on ordinary care . RESULTS Intention-to-treat analysis showed that patients treated with practice nurse-supported cognitive behavioural therapy self-help attained similar clinical outcomes for similar costs and were more satisfied than patients treated by GPs with ordinary care . On-treatment analysis showed patients receiving the facilitated cognitive behavioural therapy self-help were more likely to be below clinical threshold at 1 month compared to the ordinary care group ( odds ratio [ OR ] = 3.65 , 95 % confidence interval [ CI ] = 1.87 to 4.37 ) . This difference was less well marked at 3 months ( OR = 1.36 , 95 % CI = 0.52 to 3.56 ) . CONCLUSION Facilitated cognitive behavioural self-help may provide a short-term cost-effective clinical benefit for patients with mild to moderate anxiety and depression . This has the potential to help primary care provide a choice of effective psychological as well as pharmacological treatments for mental health problems OBJECTIVE To determine the feasibility of conducting a cluster r and omised trial in Australia of the effectiveness of general practitioner-supported delivery of internet-based cognitive behaviour therapy ( CBT ) and enhanced psychological care . DESIGN , SETTING AND PARTICIPANTS Cluster r and omised trial involving patients attending general practice s in Australia . Participating practice s were r and omly allocated to interventions . The study was conducted between January 2004 and January 2007 . INTERVENTIONS Enhanced GP care was delivered by doctors who had completed specific mental health training ; the experimental condition consisted of enhanced GP care plus MoodGYM , an internet-based CBT intervention . MAIN OUTCOME MEASURES Demographic and behavioural characteristics of patients , and demographic and practice characteristics of GPs ; time to resolution of psychological symptoms for patients involved in the longitudinal phase of the trial . RESULTS 1571 patients attending 90 GPs from 84 general practice s were identified as potentially suitable for recruitment . These patients had a mean age of 35 years , 76 % were female , 84 % had access to the internet for personal use , and 22 % reported high or very high levels of psychological distress on the Kessler Psychological Distress Scale . The 90 GPs had a mean age of 49 years , 53 % were female and 25 % had completed formal mental health training . Of the 1571 screened patients , 340 reported high levels of psychological distress , but only 140 of these could be further assessed for eligibility in the trial . Of these 140 , 83 patients with depression ( attending 10 GPs in eight general practice s ) proceeded to r and omisation . For these patients , the experimental intervention ( enhanced GP care plus MoodGYM ) tended to result in prompt and more sustained resolution of depressive symptoms . CONCLUSION Our capacity to conduct a definitive trial was limited by available re sources . Preliminary data suggest that primary care patients with depression may derive additional benefits from an internet-based CBT program delivered in conjunction with enhanced psychological care from GPs College students who have high stress levels tend to experience an increased risk of academic difficulties , substance abuse , and emotional problems . To enhance student stress management and health promoting behaviors , an online stress management intervention called MyStudentBody – Stress ( MyStudentBody – Stress ) was developed and tested . College students at six U.S. colleges were r and omized to one of three conditions : MyStudentBody – Stress , a control health information website , or no intervention . The differences between groups on stress control and health behavior measures were compared at baseline , and at 1 , 3 , and 6 months after baseline . Although there were no between-group differences on primary outcome variables , secondary analyses indicated that MyStudentBody – Stress participants were more likely to increase weekly physical activity , use specific stress management methods , and exhibit decreased anxiety and family problems . These findings indicate some potentially beneficial effects of online stress management programming for college students . Implication s for college health practitioners are discussed Objective : In two previous r and omized controlled trials Titov et al. demonstrated significant benefit from an Internet- and email-based treatment programme for social phobia . The present study ( Shyness 3 ) explores whether participants are able to complete this programme independently . Method : A total of 98 individuals with social phobia were r and omly assigned to a clinician-assisted computerized cognitive behavioural treatment ( CaCCBT ) group , a self-guided computerized CBT ( CCBT ) group , or to a waitlist control group . CaCCBT group participants completed the usual Shyness programme consisting of six online lessons , cognitive behavioural homework assignments , email contact with a therapist , and participation in an online discussion forum . CCBT group participants accessed the same re sources except for therapist emails . An intention-to-treat model was used for data analyses . Results : A total of 77 % of CaCCBT and 33 % of CCBT group participants completed all lessons . Significant differences were found after treatment between CaCCBT and control groups ( mean between-groups effect size ( ES ) for the social phobia measures = 1.04 ) , and between the CaCCBT and CCBT groups ( mean between-groups ES for the social phobia measures = 0.66 ) . No significant differences were found after treatment between the CCBT and control groups ( mean between-groups ES for the social phobia measures = 0.38 ) . CCBT participants , however , who completed the six lessons made good progress ( mean within-group ES for the social phobia measures = 0.62 ) . Quantitative and qualitative data indicate that both the CaCCBT and CCBT procedures were acceptable to participants . Conclusions : The reliability of this Internet-based treatment programme for social phobia has been confirmed . The therapist-guided condition was superior to the self-guided condition , but a subgroup of participants still benefited considerably from the latter . These data confirm that self-guided education or treatment programmes for common anxiety disorders can result in significant improvements Research on treatments for reducing pathological worry is limited . In particular , academic worry is a common theme in generalized anxiety disorder ( GAD ) sample s as well as non- clinical student sample s. Given the high cost of anxiety disorders to society , research is needed to examine the efficacy of self-administered treatments design ed to reduce pathological worry . The primary goal of this study was to investigate the benefits of three self-administered interventions for reducing academic worry . College students ( N = 113 ) experiencing clinical ly significant academic worry were r and omized to either : ( a ) worry exposure ( WE ) ; ( b ) expressive writing ( EW ) ; ( c ) relaxation consisting of pulsed audio-photic stimulation ( APS ) ; or ( d ) waitlist control ( WLC ) . Participants were instructed to practice their interventions three times per week for one month and completed home practice logs online to track treatment adherence . Academic worry , general anxiety , and perceived stress were assessed at baseline and post-treatment . Academic worry and general anxiety were also assessed at a three-month follow-up . Those assigned to the WE and APS conditions showed significant improvement relative to EW and WLC at post-treatment . All treatment conditions showed continued improvement by follow-up , with no between-group differences . Treatment and public health implication s are discussed BACKGROUND Current recommendations suggest that pharmacotherapy for patients with panic disorder should be continued for at least 1 year [ Am . J. Psychiatry 155 ( 1998 ) 1 ] , despite a paucity of data systematic ally examining outcome for periods greater than 3 - 6 months . It is critically important to obtain more information on the effectiveness of medications over time for patients who initially responded to pharmacotherapy for panic disorder . METHODS Long-term outcome was examined for 78 patients who attained a 2-month period of sustained remission on medication and received maintenance pharmacotherapy for up to 24 months during the Massachusetts General Hospital Longitudinal Study of Panic Disorder , a prospect i ve , naturalistic study . Participants were categorized by their maintenance treatment condition at remission : benzodiazepine alone ( N = 45 , 58 % ) , antidepressant alone ( N = 12 , 16 % ) , and combined treatment with a benzodiazepine and an antidepressant ( N = 21 , 27 % ) . RESULTS Approximately half ( N = 36 , 46 % ) of the patients who had achieved remission relapsed at some time over the 2-year naturalistic study period , despite continued and adequate pharmacotherapy . There was no difference in timing or frequency of relapse by type of maintenance pharmacotherapy . LIMITATIONS Interpretation of the data is limited by the naturalistic nature of the study , and by the relatively low sample size . CONCLUSIONS This data suggests that patients with panic disorder have a high rate of relapse even after acute response to pharmacotherapy , despite continued treatment . In addition , the use of combined pharmacotherapy with antidepressants and benzodiazepines does not appear to provide greater protection from relapse than monotherapy Abstract This article reports the initial results of a prospect i ve study on the prevalence of psychiatric disorders in the Dutch population aged 18–64 . The objectives and the design of the study are described elsewhere in this issue . A total of 7076 people were interviewed in person in 1996 . The presence of the following disorders was determined by means of the CIDI : mood disorders , anxiety disorders , eating disorders , schizophrenia and other non-affective psychoses , and substance use disorders . Psychiatric disorders were found to be quite common . Some 41.2 % of the adult population under 65 had experienced at least one DSM-III-R disorder in their lifetime , among them 23.3 % within the preceding year . No gender differences were found in overall morbidity . Depression , anxiety , and alcohol abuse and dependence were most prevalent , and there was a high degree of comorbidity between them . The prevalence rate encountered for schizophrenia was lower ( 0.4 % lifetime ) than generally presumed . A comparison with findings from other countries is made . Relevant determinants of psychiatric morbidity were analysed Objective : The present study ( Shyness 7 ) has two aims : Firstly , to replicate an earlier trial showing that a self-guided Internet treatment for social phobia is efficacious , and secondly , to examine whether the addition of self-guided motivational enhancement strategies improves completion rates and clinical outcomes . Method : R and omized controlled trial ( RCT ) of self-guided Internet-based cognitive behavioural treatment ( iCBT ) , or iCBT plus self-guided motivational enhancement strategies ( iCBT+MS ) , was conducted . An intention-to-treat and last observation carried forward model was used for data analyses . The participants consisted of 108 volunteers with social phobia . The iCBT intervention consisted of two online lessons about symptoms and treatment of anxiety disorders and six lessons about management of social phobia ( the Shyness programme ) with complex automated reminders . The motivational intervention was based on traditional techniques including underst and ing and exploring ambivalence about change using a cost – benefit analysis , developing and resolving discrepancy between values and symptoms , and enhancing self-efficacy for change . The main outcome measures were the Social Interaction Anxiety Scale and Social Phobia Scale . Results : More iCBT+MS group participants completed the eight lessons than iCBT group participants ( 75 % versus 56 % , respectively ) , but there were no between-group differences in outcome measures at post-treatment or at 3 month follow up . Large mean within-groups effect sizes ( Cohen 's d ) for the two social phobia measures were found for both the iCBT and iCBT+ MS groups ( 1.1 and 0.95 , respectively ) , which were sustained at 3 month follow up ( 1.06 and 1.07 , respectively ) . Both iCBT and iCBT+MS group participants reported that the procedures were highly acceptable . Conclusions : Both self-guided versions of the Shyness programme were reliably efficacious , confirming that people with social phobia may significantly benefit from a highly structured self-guided intervention . The addition of motivational techniques increased completion rates but did not improve clinical outcomes or acceptability Objective : Social phobia can be treated by brief Internet-based cognitive behaviour therapy ( CBT ) . Most people with social phobia , however , meet criteria for another mental disorder ; this comorbidity is associated with significant disability , and cases of comorbidity may be more difficult to treat . The present study examined the impact of the Shyness programme , an Internet-based treatment programme for social phobia , on comorbid symptoms of depression and generalized anxiety disorder . Method : Data from three r and omized controlled trials using the Shyness programme to treat social phobia were reanalysed . The 211 subjects , all of whom met DSM-IV criteria for social phobia , were divided into four groups : ( i ) social phobia only ; ( ii ) social phobia with elevated symptoms of depression ; ( iii ) social phobia with elevated symptoms of generalized anxiety ; and ( iv ) social phobia with elevated symptoms of both generalized anxiety and depression . The improvement in social phobia , depression and anxiety following Internet-based treatment for social phobia was measured . Results : Improvement in social phobia was seen in all groups , whether comorbid or not . Significant improvements in comorbid symptoms of depression and generalized anxiety occurred even though the treatment was focused on the social phobia . Conclusions : Brief Internet-based CBT can reduce both the target disorder as well as comorbid symptoms . These findings are consistent with evidence that unified or transdiagnostic programmes may reduce the severity of comorbid disorders and symptoms , indicating an important direction for future research BACKGROUND Long-term follow-up has rarely been reported after self-exposure therapy for phobias . AIMS Completion of such a follow-up . METHOD Two-year follow-up was achieved in 68 ( 85 % ) of 80 patients with phobias who had completed a previous 14-week r and omised controlled trial comparing therapist-accompanied self-exposure , self-exposure or self-relaxation . Measures were self-reported ratings of symptoms , satisfaction and use of other treatment . RESULTS Improvement at week 14 was maintained 2 years later . Clinician-accompanied exposure and self-exposure did not differ on any measure . Compliance with self-exposure homework during weeks 0 - 8 predicted more improvement 2 years later . Patients who failed to improve with relaxation by week 14 improved after subsequent crossover to exposure . A need for more treatment for their phobias was still felt by 33 patients ( 49 % ) . CONCLUSIONS Patients with phobias maintained their improvement to 2-year follow-up after the end of self-exposure therapy Previous studies on Internet-based treatment with minimal to moderate therapist guidance have shown promising results for a number of specific diagnoses . The aim of this study was to test a new approach to Internet treatment that involves tailoring the treatment according to the patient 's unique characteristics and comorbidities . A total of 54 participants , regardless of specific anxiety diagnosis , were included after an in-person , semi-structured diagnostic interview and r and omized to a 10 week treatment program or to a control group . Treatment consisted of a number of individually-prescribed modules in conjunction with online therapist guidance . Significant results were found for all dependent measures both immediately following treatment and at 1 and 2 year intervals . Mean between-group effect size including measures of anxiety , depression and quality of life was Cohen 's d = 0.69 at post-treatment , while the mean within-group effect size was d = 1.15 at post-treatment and d = 1.13 and d = 1.04 at 1 and 2 year follow-up respectively . The tentative conclusion drawn from these results is that tailoring the Internet-based therapy can be a feasible approach in the treatment of anxiety in a homogeneous population 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 The present study investigated the effectiveness of bibliotherapy and minimal therapist-contact interventions in the treatment of panic attacks . Individuals were r and omly assigned to one of three conditions : ( 1 ) bibliotherapy alone ( BT ) ; ( 2 ) bibliotherapy plus phone contact ( BT+PC ) ; or ( 3 ) phone contact alone ( PC ) . Assessment ( pre- and post-treatment ) and treatment ( 8 weeks in duration ) were conducted via mail and phone . Individuals receiving BT and BT+PC exhibited significant reductions from pre- to post-treatment on panic cognitions and fear of having a panic attack . Individuals receiving BT+PC exhibited significant reductions from pre- to post-treatment on panic symptoms and avoidance . In addition , individuals in the BT and BT+PC groups were more likely to exhibit clinical ly significant improvement on most dependent measures relative to PC alone . On some measures , individuals in the BT+PC group did clinical ly better than individuals in the BT group . Results of the present study also suggest that diagnosis may play some role in outcome Generalized anxiety disorder ( GAD ) has been effectively treated with cognitive behavioural therapy ( CBT ) in face-to face setting s. Internet-delivered CBT could be a way to increase the accessibility and affordability of CBT for people suffering from GAD . The aim of this study was to evaluate the efficacy of guided Internet-delivered CBT for GAD in a controlled trial with a wait-list control group . A total of 89 participants were included following online screening and a structured psychiatric telephone interview . Participants were r and omized to either an 8-week treatment group ( n = 44 ) or a wait-list control group ( n = 45 ) . Treatment consisted of a self-help program based on CBT principles and applied relaxation along with therapist guidance . The main outcome measure was the Penn State Worry Question naire . Ratings of clinical improvement and symptoms were included as well as secondary outcome measures dealing with anxiety , depression , and quality of life . Among the treatment group participants , 13.6 % did not complete the posttreatment measures . The treatment group showed significant improvement compared with the control group on all outcome measures . Large effect sizes ( Cohen 's d>0.8 ) were found both within the treatment group and between the groups in favor of the treatment on all outcome measures except on a measure of quality of life . Results at 1- and 3-year follow-up indicated that treatment results improved or were maintained . The authors conclude that Internet-delivered CBT with therapist support can reduce symptoms and problems related to GAD After initial interviews with 20,291 adults in the National Institute of Mental Health Epidemiologic Catchment Area Program , we estimated prospect i ve 1-year prevalence and service use rates of mental and addictive disorders in the US population . An annual prevalence rate of 28.1 % was found for these disorders , composed of a 1-month point prevalence of 15.7 % ( at wave 1 ) and a 1-year incidence of new or recurrent disorders identified in 12.3 % of the population at wave 2 . During the 1-year follow-up period , 6.6 % of the total sample developed one or more new disorders after being assessed as having no previous lifetime diagnosis at wave 1 . An additional 5.7 % of the population , with a history of some previous disorder at wave 1 , had an acute relapse or suffered from a new disorder in 1 year . Irrespective of diagnosis , 14.7 % of the US population in 1 year reported use of services in one or more component sectors of the de facto US mental and addictive service system . With some overlap between sectors , specialists in mental and addictive disorders provided treatment to 5.9 % of the US population , 6.4 % sought such services from general medical physicians , 3.0 % sought these services from other human service professionals , and 4.1 % turned to the voluntary support sector for such care . Of those persons with any disorder , only 28.5 % ( 8.0 per 100 population ) sought mental health/addictive services . Persons with specific disorders varied in the proportion who used services , from a high of more than 60 % for somatization , schizophrenia , and bipolar disorders to a low of less than 25 % for addictive disorders and severe cognitive impairment . Applications of these descriptive data to US health care system reform options are considered in the context of other variables that will determine national health policy Objective The purpose of this study was to determine if a novel workplace stress management program , delivered either face-to-face or by self-help , would reduce illness and health services utilization among participants . Methods Five hundred one volunteers were r and omly allocated to one of three groups : full intervention , which received assessment and personalized self- study feedback and was offered six face-to-face , small-group sessions ; partial intervention , a self-help group that received assessment and personalized feedback by mail ; and a wait-list control group . All participants completed question naires for stress , anxiety , and coping at the start of the study and 6 and 12 months later . Health reports were completed at 0 , 3 , 6 , 9 , and 12 months . A sub sample of subjects who subscribed to a single health maintenance organization provided objective ly recorded doctor visit data across the study year . Results All three groups reported significant improvement in their stress , anxiety , and coping across the year . Full intervention participants showed a more rapid reduction in negative responses to stress than did participants from the other groups . Full-intervention subjects also reported fewer days of illness than subjects in the other groups . Objective ly measured physician visits showed a large ( 34 % ) reduction in healthcare utilization for full intervention subjects in the HMO sub sample . Conclusions These results indicated that a work-site program that focuses on stress , anxiety , and coping measurement along with small-group educational intervention can significantly reduce illness and healthcare utilization OBJECTIVE This study evaluated a 10-week Internet-based bibliotherapy self-help program with short weekly telephone calls for people suffering from panic disorder with or without agoraphobia . METHOD After the authors confirmed the diagnosis by administering the Structured Clinical Interview for DSM-IV by telephone , 60 participants were r and omly assigned to either a wait-listed control group or a multimodal treatment package based on cognitive behavior therapy plus minimal therapist contact via e-mail . A 10-minute telephone call was made each week to support each participant . Total mean time spent on each participant during the 10 weeks was 3.9 hours . The participants were required to send in homework assignments before receiving the next treatment module . RESULTS Analyses were conducted on an intention-to-treat basis , which included all r and omly assigned participants . From pretreatment to posttreatment , all treated participants improved significantly on all measured dimensions ( bodily interpretations , maladaptive cognitions , avoidance , general anxiety and depression levels , and quality of life ) . Treatment gains on self-report measures were maintained at the 9-month follow-up . A blind telephone interview after the end of treatment revealed that 77 % of the treated patients no longer fulfilled the criteria for panic disorder , whereas all of the wait-listed subjects still suffered from it . CONCLUSIONS This study provides evidence to support the use of treatment distributed via the Internet with the addition of short weekly telephone calls to treat panic disorder . Replication should be made to compare self-help and telephone treatment based on cognitive behavior methods with nonspecific interventions A new cognitive therapy ( CT ) program was compared with an established behavioral treatment . Sixty-two patients meeting Diagnostic and Statistical Manual of Mental Disorders ( 4th ed . ; American Psychiatric Association , 1994 ) criteria for social phobia were r and omly assigned to CT , exposure plus applied relaxation ( EXP = AR ) , or wait-list ( WAIT ) . CT and EXP = AR were superior to WAIT on all measures . On measures of social phobia , CT led to greater improvement than did EXP = AR . Percentages of patients who no longer met diagnostic criteria for social phobia at posttreatment-wait were as follows : 84 % in CT , 42 % in EXP = AR , and 0 % in WAIT . At the 1-year follow-up , differences in outcome persisted . In addition , patients in EXP = AR were more likely to have sought additional treatment . Therapist effects were small and nonsignificant . CT appears to be superior to EXP = AR in the treatment of social phobia Background : As many sufferers from phobic and panic ( phobia/panic ) disorders can not get to suitable therapists , routine aspects of therapy were delegated to internet-accessed computer-aided self-help with or without exposure instructions . Methods : Phobia/panic referrals were r and omised to computer-aided self-help via the internet at home in a 2:1 ratio either by self-exposure cognitive behaviour therapy ( CBT ) [ FearFighter ( FF ) , n = 45 ] or by minimal CBT without exposure [ Managing Anxiety ( MA ) , n = 23 ] . All had brief backup phone advice from a clinician concerning their computer guidance . Results : On self-ratings and blinded assessor ratings , patients improved equally with each form of self-help over 10 treatment weeks but significantly more on 5 out of 10 measures by week 14 ( 1-month follow-up ) when the self-help included self-exposure instructions than when it did not . In accord with this , st and ardised effect sizes ( Cohen ’s d ) indicated superiority of FF over MA on 5 measures by week 14 . Satisfaction with treatment in all patients pooled correlated positively with improvement after treatment and at 1-month follow-up . Conclusions : At the end of treatment , computer-aided CBT self-help at home via the internet plus brief live helpline support was effective with or without exposure instructions , and at 1-month follow-up it was more effective on some measures if exposure instructions had been included . Analysis is needed of how non-exposure CBT produced its shorter-term effect BACKGROUND Severe health anxiety is a common condition associated with functional disability , making it a costly disorder from a societal perspective . Internet-based cognitive behaviour therapy ( ICBT ) is a promising treatment but no previous study has assessed the cost-effectiveness or long-term outcome of ICBT for severe health anxiety . The aim of this study was to investigate the cost-effectiveness and 1-year treatment effects of ICBT for severe health anxiety . METHOD Cost-effectiveness and 1-year follow-up data were obtained from a r and omized controlled trial ( RCT ) comparing ICBT ( n = 40 ) to an attention control condition ( CC , n = 41 ) . The primary outcome measure was the Health Anxiety Inventory ( HAI ) . A societal perspective was taken and incremental cost-effectiveness ratios ( ICERs ) were calculated using bootstrap sampling . RESULTS The main ICER was -£1244 , indicating the societal economic gain for each additional case of remission when administering ICBT . Baseline to 1-year follow-up effect sizes on the primary outcome measure were large ( d = 1.71 - 1.95 ) . CONCLUSIONS ICBT is a cost-effective treatment for severe health anxiety that can produce substantial and enduring effects BACKGROUND Controlled prospect i ve studies of the simultaneous long-term outcome of several mental disorders are rare . This study sought to determine if there were important differences between the outcome of anxiety and depressive disorders after 12 years and to examine their main predictors . METHOD A cohort of 210 people seen in general practice psychiatric clinics with a DSM-III diagnosis of generalized anxiety disorder ( 71 ) , panic disorder ( 74 ) , or dysthymic disorder ( 65 ) , including combined anxiety-depressive disorder ( cothymia ) ( 67 ) was followed up after 12 years . Interview assessment s of symptoms , social functioning and outcome were made , the latter using a new scale , the Neurotic Disorder Outcome Scale . Seventeen baseline predictors were also examined . RESULTS Data were obtained from 201 ( 96 % ) patients , 17 of whom had died . Only 73 ( 36 % ) had no DSM diagnosis at the time of follow-up . Using univariate and stepwise multiple linear regression those with cothymia , personality disorder , recurrent episodes and greater baseline self-rated anxiety and depression ratings had a worse outcome than others ; initial diagnosis did not contribute significantly to outcome and instability of diagnosis over time was much more common than consistency . CONCLUSION Only two out of five people with the common neurotic disorders have a good outcome despite alleged advances in treatment . Those with greater mood symptoms and pre-morbid personality disorder have the least favourable outcome . It is suggested that greater attention be paid to the concurrent treatment of personality disorder and environmental factors rather than symptoms as these may be the real cause of apparent treatment resistance Due to treatment accessibility and cost issues , interest in self-help programs ( e.g. , bibliotherapy , telehealth ) for common psychological disorders is growing . Research supporting the efficacy of such a program for social anxiety , however , is limited . The present study examined the efficacy of an 8-week self-directed cognitive behavioral treatment with minimal therapist involvement for social phobia based on a widely available self-help book . Twenty-one adults with social phobia initially received either treatment ( i.e. assigned readings in the workbook with limited therapist contact ) or were wait-listed . Wait-listed patients eventually received the same self-directed treatment . Results revealed that the self-help/minimal therapist contact treatment was superior to wait-list on most outcome measures . Across the entire sample , reductions in social anxiety , global severity , general anxiety , and depression were observed at posttest and 3-month follow-up . These findings provide preliminary support for using this self-help workbook for individuals with mild to moderate social anxiety in conjunction with infrequent therapist visits to reinforce the treatment principles . Study limitations and future directions are discussed A r and omized trial was conducted of two different self-help programs for panic disorder ( PD ) on the Internet . After confirming the PD-diagnosis with an in-person structured clinical interview for DSM-IV ( SCID ) interview 22 participants were r and omized to either applied relaxation ( AR ) or a multimodal treatment package based on cognitive behavioral therapy ( CBT ) . Overall , the results suggest that Internet-administered self-help plus minimal therapist contact via e-mail has a significant medium to large effect ( Cohen 's d=0.71 for AR and d=0.42 for CBT ) . The results from this study generally provide evidence to support the continued use and development of Internet-distributed self-help programs BACKGROUND Group cognitive behavioral treatments ( GCBTs ) for hoarding have produced modest benefits . The current study examined whether the outcomes of a specialized GCBT improve upon bibliotherapy ( BIB ) for hoarding , as part of a stepped care model . We also explored whether additional home assistance enhanced GCBT outcomes . METHODS Hoarding patients ( n = 38 ) were r and omized and completed one of three conditions : ( 1 ) GCBT with nonclinician home assistants ( GCBT+HA ; N = 11 ) , ( 2 ) GCBT without HA ( CGBT ; N = 14 ) , and ( 3 ) BIB ( N = 13 ) . All GCBT participants received 20 weekly group sessions and four home visits by a group co-therapist . GCBT+HA groups received four additional visits by a nonclinician coach . BIB participants were assigned a self-help book describing specific skills to reduce hoarding over the 20-week period . All participants were assessed by self-report at baseline , mid-treatment , and posttreatment . The sample averaged 57 years old and was mainly female , White , highly educated , employed , and living alone . RESULTS GCBT+HA and GCBT participants showed significant reductions on hoarding and depression symptoms , whereas BIB did not . GCBT+HA and GCBT benefited substantially and similarly on the saving inventory-revised ( reductions of 29.9 and 23.3 % , respectively ) and SI-R ( Saving Inventory-Revised ) ( reductions of 26.5 and 25.4 % ) , whereas BIB participants showed very limited improvement ( 9 % reduction ) on both measures . CONCLUSION This study provides support for the efficacy of GCBT for hoarding . The effect of adding nonclinician home assistance was not significant in this small sample . BIB was not sufficient to improve hoarding symptoms . The findings have implication s for a stepped care model for treating hoarding ( e.g. , the benefits of psycho-education via BIB , added benefits of extra in-home visits ) and suggest the need to further examine the role of in-home hoarding coaches Abstract Objective : To determine whether inappropriate subgroup analysis together with chance could change the conclusion of a systematic review of several r and omised trials of an ineffective treatment . Design : 44 r and omised controlled trials of DICE therapy for stroke were performed ( simulated by rolling different coloured dice ; two trials per investigator ) . Each roll of the dice yielded the outcome ( death or survival ) for that “ patient . ” Publication bias was also simulated . The results were combined in a systematic review . Setting : Edinburgh . Main outcome measure — Mortality . Results : The “ hypothesis generating ” trial suggested that DICE therapy provided complete protection against death from acute stroke . However , analysis of all the trials suggested a reduction of only 11 % ( SD 11 ) in the odds of death . A predefined subgroup analysis by colour of dice suggested that red dice therapy increased the odds by 9 % ( 22 ) . If the analysis excluded red dice trials and those of poor method ological quality the odds decreased by 22 % ( 13 , 2P=0.09 ) . Analysis of “ published ” trials showed a decrease of 23 % ( 13 , 2P=0.07 ) while analysis of only those in which the trialist had become familiar with the intervention showed a decrease of 39 % ( 17 , 2P=0.02 ) . Conclusion : The early benefits of DICE therapy were not confirmed by subsequent trials . A plausible ( but inappropriate ) subset analysis of the effects of treatment led to the qualitatively different conclusion that DICE therapy reduced mortality , whereas in truth it was ineffective . Chance influences the outcome of clinical trials and systematic review s of trials much more than many investigators realise , and its effects may lead to incorrect conclusions about the benefits of treatment Behavioural methods of treating anxiety have been shown to be highly effective but are not widely available in general practice where most people suffering from anxiety are treated . This study reports a development in service delivery which is simple , inexpensive and does not make great time dem and s on general practitioners or require them to extend their training and expertise . The study shows that for patients suffering from panic disorder or generalized anxiety disorder the use of an anxiety management booklet in addition to their usual treatment from their general practitioner produces clinical ly and statistically significant improvements . Of particular importance is the speed of response to the booklet . Within the first two weeks those patients who received the booklet were significantly less anxious than the controls . The booklet was acceptable to patients and recommendations are made about how to incorporate it into clinical practice The aim of this work was to test the contribution of cognitive therapy to exposure in vivo in the group treatment of generalized social phobia . Seventy-one severely disabled social phobics , selected according to DSM-III-R criteria , were assigned at r and om to : ( a ) self-exposure in vivo , ( b ) self-exposure in vivo with cognitive therapy , or ( c ) a waiting-list control group . A multigroup experimental design with repeated measures of assessment ( pretreatment , posttreatment , and 1- , 3- , 6- , and 12-month follow-ups ) was used . Additionally , half of the patients in both therapeutic groups were given self-help manuals for managing anxiety . Most patients that were treated ( 64 % ) showed significant improvement at the 12-month follow-up , but there were no differences between the two therapeutic modes . No improvement was shown by the control-group participants at the 6-month follow-up . The results of the present trial do not support the beneficial effects of adding cognitive therapy or a self-help manual to exposure alone . Finally , several topics that may contribute to future research in this field are discussed OBJECTIVES . To evaluate the effectiveness of a two session guided self-help ( GSH ) intervention provided by primary care graduate mental health workers ( PCGMHWs ) in a primary care mental health service . DESIGN . Pragmatic r and omized trial , with a wait list control design . METHOD . Patients presenting with significant anxiety and depression problems were given one or more self-help booklets at screening and r and omly allocated to an immediate ( ITG ) or delayed treatment group ( DTG ) . Following this , a two-session GSH intervention was provided by one of two PCGMHWs , with a review session to decide on the need for further intervention . The DTG began the intervention 8 weeks after the screening and the primary outcome was Clinical Outcomes in Routine Evaluation - Outcome Measure ( CORE-OM ) scores after 8 weeks . RESULTS . A total of 63 patients were allocated to the ITG , 59 to the DTG . Analysis of covariance , carried out on an intention to treat basis , showed a significant treatment effect , F(1,98 ) = 15 , p < .001 , and a comparison of means at 8 weeks showed a significant difference , t(116 ) = 2.1 ( 95 % CI [ 1.1 , 5.9 ] ) , p= .042 with an effect size , d= 0.375 . Taking the two groups together , CORE-OM scores for patients who completed the intervention reduced between screening and the review session by an average of 7.9 ( 95 % CI [ 6.3 , 9.5 ] ) , effect size of 1.2 . Between screening and the review session , 47 % showed a reliable and clinical ly significant improvement . CONCLUSIONS . The study provides some support for the effectiveness of a two-session GSH intervention and a stepped-care service model In this study conducted in the French-speaking part of Switzerl and , 52 individuals with social phobia were r and omly assigned either to an Internet-based cognitive-behavioral treatment with minimal contact with therapists via e-mail or to a waiting-list control group . Significant differences between the two groups were found at posttreatment on all primary outcome measures ( social anxiety measures ) and on two of the secondary outcome measures ( general symptomatology , therapy goal attainment ) . On average , within-groups effect sizes were large for the primary outcomes ( Cohen 's d=0.82 ) and for secondary outcomes ( Cohen 's d=1.04 ) . Moreover , subjects in the treatment group fulfilled the criteria of clinical ly significant improvement significantly more often than subjects in the control group on all measured dimensions ( 58 % vs. 20 % ) . Users ' acceptance of the program was high . The results from the present study lend further support to the hypothesis that Internet-delivered interventions with minimal therapist contact are a promising treatment approach to social phobia Background : Guided Internet-based cognitive behavior therapy ( ICBT ) has been tested in many trials and found to be effective in the treatment of anxiety and mood disorders . Generalized anxiety disorder ( GAD ) has also been treated with ICBT , but there are no controlled trials on guided Internet-based psychodynamic treatment ( IPDT ) . Since there is preliminary support for psychodynamic treatment for GAD , we decided to test if a psychodynamically informed self-help treatment could be delivered via the Internet . The aim of the study was to investigate the efficacy of IPDT for GAD and to compare against ICBT and a waiting list control group . Method : A r and omized controlled superiority trial with individuals diagnosed with GAD comparing guided ICBT ( n = 27 ) and IPDT ( n = 27 ) against a no treatment waiting list control group ( n = 27 ) . The primary outcome measure was the Penn State Worry Question naire . Results : While there were no significant between-group differences immediately after treatment on the main outcome measure , both IPDT and ICBT result ed in improvements with moderate to large within-group effect sizes at 3 and 18 months follow-up on the primary measure in the completer analyses . The differences against the control group , although smaller , were still significant for both PDT and CBT when conforming to the criteria of clinical ly significant improvement . The active treatments did not differ significantly . There was a significant group by time interaction regarding GAD symptoms , but not immediately after treatment . Conclusions : IPDT and ICBT both led to modest symptom reduction in GAD , and more research is needed Risk of withdrawal was investigated in a prospect i ve , double-blind comparison of clorazepate dipotassium , a benzodiazepine with a long half-life , and the nonbenzodiazepine buspirone hydrochloride in the long-term treatment of anxious out patients . Patients were treated with therapeutic doses of clorazepate dipotassium ( 15 to 60 mg/d ) or buspirone hydrochloride ( 10 to 40 mg/d ) for six continuous months before their tranquilizer therapy was blindly and abruptly stopped . There was a significant increase in symptom severity consistent with a withdrawal reaction for the clorazepate group but not the buspirone group . For the clorazepate group , there was a suggestion that previous discontinuous exposure to benzodiazepines might sensitize patients to subsequent withdrawal effects . For the buspirone group , a higher dropout rate raised questions about patient satisfaction with therapy in this rather chronically anxious population Objective : To evaluate the suitability and acceptability of computerised cognitive behaviour therapy ( CCBT ) . Method : Participants were patients who had been referred to a secondary care service in the usual manner , and then offered participation in a r and omised controlled trial comparing the efficacy of CCBT with a control condition ( waitlist ) for patients with a current primary diagnosis of generalised anxiety disorder , panic disorder or social phobia . Data were collected regarding the recruitment and retention of patients , and patient ratings ( anchored Likert scales ) of treatment credibility , treatment satisfaction , treatment acceptability and telephone support . Results : A total of 1141 referrals were received by the secondary care service . Of the 1141 , 748 ( 66 % ) were not suitable for the study , 178 ( 16 % ) declined to participate and 127 ( 11 % ) were not contactable . Therefore , of the 1141 patients referred to the secondary care service , only 88 patients ( 8 % ) were eligible and consenting for the study . The single most common reason for patients not being suitable for the study was that the referral was urgent . In a clinical setting where CCBT could be used alongside clinical management , many of these patients may have been suitable for CCBT . Of the patients r and omised to treatment ( n = 40 ) , 65 % completed treatment . Drop-out rates were not significantly different across diagnostic groups . The single most commonly cited reason for not completing treatment was ‘ too busy ’ . Patient ratings of treatment were typically favourable ( credibility , satisfaction , acceptability and telephone support ) . Conclusions : CCBT was typically rated favourably by patients referred to a secondary care service and r and omised to treatment . However , only a small minority of patients was eligible and consenting for the trial . Therefore , while CCBT may be an acceptable treatment , its suitability for secondary care setting s remains unclear BACKGROUND Cognitive-behavioural therapy ( CBT ) brings about significant clinical improvement in anxiety and depression , but therapists are in short supply . We report the first phase of a r and omized controlled trial of an interactive multimedia program of cognitive-behavioural techniques , Beating the Blues ( BtB ) , in the treatment of patients in general practice with anxiety , depression or mixed anxiety/depression . METHOD One hundred and sixty-seven adults suffering from anxiety and /or depression and not receiving any form of psychological treatment or counselling were r and omly allocated to receive , with or without medication , BtB or treatment as usual ( TAU ) . Measures were taken on five occasions : prior to treatment , 2 months later , and at 1 , 3 and 6 months follow-up using the Beck Depression Inventory , Beck Anxiety Inventory and Work and Social Adjustment Scale . RESULTS Patients who received BtB showed significantly greater improvement in depression and anxiety compared to TAU by the end of treatment ( 2 months ) and to 6 months follow-up . Symptom reduction was paralleled by improvement in work and social adjustment . There were no interactions of BtB with concomitant pharmacotherapy or duration of illness , but evidence , on the Beck Anxiety Inventory only , of interaction with primary care practice . Importantly , there was no interaction between the effects of BtB and baseline severity of depression , from which we conclude that the effects of the computer program are independent of starting level of depression . CONCLUSIONS These results demonstrate that computerized interactive multimedia cognitive-behavioural techniques under minimal clinical supervision can bring about improvements in depression and anxiety , as well as in work and social adjustment , with and without pharmacotherapy and in patients with pre-treatment illness of duration s greater or less than 6 months . Thus , our results indicate that wider dissemination of cognitive-behavioural techniques is possible for patients suffering from anxiety and /or depression A r and omized trial was conducted comparing 10 individual weekly sessions of cognitive behaviour therapy for panic disorder ( PD ) with or without agoraphobia with a 10-module self-help program on the Internet . After confirming the PD diagnosis with an in-person structured clinical interview ( SCID ) 49 participants were r and omized . Overall , the results suggest that Internet-administered self-help plus minimal therapist contact via e-mail can be equally effective as traditional individual cognitive behaviour therapy . Composite within-group effect sizes were high in both groups , while the between-group effect size was small ( Cohen 's d=16 ) . One-year follow-up confirmed the results , with a within-group effect size of Cohen 's d=0.80 for the Internet group and d=0.93 for the live group . The results from this study generally provide evidence to support the continued use and development of Internet-distributed self-help programs Investigated the efficacy of self-administered cognitive therapy ( RET ) in the treatment of high and chronic social anxiety . Forty-five socially anxious volunteer students , who scored in the upper 15 % of 570 students prescreened with the Social Avoidance and Distress Scale , were matched on SAD scores and r and omly assigned to self-administered cognitive therapy ( RET ) , a self-administered attention placebo condition ( Logo-therapy ) , or a no-treatment control condition . Pretest and posttest measures included the Social Avoidance and Distress Scale ( SAD ) , Fear of Negative Evaluation Scale ( FNE ) , State-Trait Anxiety Inventory , and Rotter 's Internal-External Locus of Control Scale . Results indicated that self-administered cognitive therapy significantly decreased social anxiety and fear of negative evaluation and also suggested a generalization of effects as trait anxiety significantly decreased . Comparisons of mean change scores with therapist administered studies lend support to the conclusion that self-administered cognitive restructuring is an effective means of decreasing social-evaluative anxiety . Mean change scores suggest that participants may have attained therapeutic benefits as a consistent trend toward decreased anxiety across variables BACKGROUND Internet-delivered treatment may reduce barriers to care in those unwilling or unable to access traditional forms of treatment . OBJECTIVE To assesses the efficacy of web-based therapist-assisted cognitive behavioral treatment ( web-CBT ) of panic symptoms . DESIGN A r and omized waiting-list controlled trial with an uncontrolled three-year follow-up . PARTICIPANTS A community sample of 58 participants with chronic panic symptoms of varying severity ( immediate treatment : n=27 , waiting-list control : n=31 ) . OUTCOME MEASURES The primary outcome measures were a one-week Panic Diary and the Panic Disorder Severity Scale - Self-Report ( PDSS-SR ) ; secondary measures were the Agoraphobic Cognitions Question naire ( ACQ ) , the Body Sensations Question naire ( BSQ ) , the Mobility Inventory - Alone subscale ( MI-AAL ) , and the Depression Anxiety Stress Scales ( DASS-42 ) . RESULTS In the RCT , 54 participants ( 93 % ) completed posttest measurements . With regard to the primary outcome measures , intention-to-treat ANCOVAs revealed that participants in the treatment condition improved more than the participants in the waiting-list control condition ( p<.03 ) , with a pooled between-group effect size of d=.7 . After three years ( n=47 ; 81 % study compliance ) , effects were more pronounced . CONCLUSION The results demonstrate the efficacy of therapist-assisted web-CBT in the treatment of panic symptoms BACKGROUND Anxiety disorders are prevalent in primary care . Psychological treatment is effective but time-consuming , and there are waiting lists for secondary care . Interest has therefore grown in developing guidelines for treatment that would be feasible in primary care . AIM To compare the effectiveness and feasibility of guided self-help , the Anxiety Disorder Guidelines of the Netherl and s College of General Practitioners and cognitive behavioural therapy ( CBT ) . DESIGN OF STUDY R and omised controlled study lasting 12 weeks with follow-up at 3 and 9 months for primary care patients with panic disorder and /or generalised anxiety disorder . SETTING The first two forms of treatment were carried out by 46 GPs who were r and omly assigned to one or the other form . CBT was carried out by cognitive behaviour therapists in a psychiatric outpatient clinic . METHOD Participants ( n = 154 ) were r and omly assigned to one of the three forms of treatment . The main outcome measure used was the state subscale of the Spielberger Anxiety Inventory . RESULTS All three forms of treatment gave significant improvement between pre-test and post-test , and this improvement remained stable between post-test and the follow-ups . The results obtained with the three treatment forms did not differ significantly over time . The feasibility of the Anxiety Disorder Guidelines was low compared with that of guided self-help . CONCLUSION Our results indicate that primary care patients with prevalent anxiety disorders for whom the GP does not find referral necessary can be adequately treated by the GP . Psychiatric outpatient clinic referral does not give superior results . Guided self-help is easier for the GP to carry out than a less highly-structured treatment like that laid down in the Anxiety Disorder Guidelines OBJECTIVE The effectiveness of self-help material s may be constrained by failures to undertake recommended exercises or to deploy the techniques that one has learned at the critical moment . The present r and omized controlled trial investigated whether augmenting self-help material s with if-then plans ( or implementation intentions ) could overcome these problems and enhance the self-management of anxiety symptoms . METHOD At baseline , participants who reported anxiety symptoms completed the Hospital Anxiety and Depression Scale ( HADS ) and the state version of the State-Trait Anxiety Inventory ( STAI ) . Participants were then r and omized via a computer program to st and ard self-help ( n = 86 ) , augmented self-help ( n = 90 ) , or no-intervention ( n = 86 ) conditions . Eight weeks later , 95 % ( n = 249 ) of the participants completed the HADS and STAI again . RESULTS Findings showed a significant reduction in anxiety in the augmented self-help condition compared with both the st and ard self-help and no-intervention conditions ( caseness rates on the HADS at follow-up were 21 % , 49 % , and 44 % , respectively ) . Mediation analyses indicated that the benefits of augmented self-help material s were explained by improved detection of anxiety-related triggers and greater experienced benefits of the self-help techniques . CONCLUSIONS These findings suggest that implementation intentions offer a valuable supplement to self-help material s that can enhance their impact on outcomes BACKGROUND Cognitive-behavioural therapy ( CBT ) is effective for treating anxiety and depression in primary care , but there is a shortage of therapists . Computer-delivered treatment may be a viable alternative . AIMS To assess the cost-effectiveness of computer-delivered CBT . METHOD A sample of people with depression or anxiety were r and omised to usual care ( n=128 ) or computer-delivered CBT ( n=146 ) . Costs were available for 123 and 138 participants , respectively . Costs and depression scores were combined using the net benefit approach . RESULTS Service costs were 40 British pounds ( 90 % CI - 28 British pounds to 148 British pounds ) higher over 8 months for computer-delivered CBT . Lost-employment costs were 407 British pounds ( 90 % CI 196 British pounds to 586 British pounds ) less for this group . Valuing a 1-unit improvement on the Beck Depression Inventory at 40 British pounds , there is an 81 % chance that computer-delivered CBT is cost-effective , and it revealed a highly competitive cost per quality -adjusted life year . CONCLUSIONS Computer-delivered CBT has a high probability of being cost-effective , even if a modest value is placed on unit improvements in depression Objective : To determine the efficacy of an Internet-based clinician-assisted cognitive behavioural treatment program ( the Panic program ) for panic disorder ( with or without agoraphobia ) . Method : Fifty-nine individuals meeting diagnostic criteria for panic disorder with agoraphobia were r and omly assigned to a treatment group or to a waitlist control group . Treatment group participants completed the Panic program , comprising six on-line lessons , weekly homework assignments , received weekly email contact from a psychiatry registrar , and contributed to a moderated online discussion forum with other participants . An intention-to-treat model was used for data analyses . Results : Twenty-three ( 79 % ) of treatment group participants completed all lessons within the 8-week program , and post-treatment data were collected from 22/29 treatment group and 22/25 waitlist group participants . Compared to the control group , treatment group participants reported significantly reduced symptoms of panic as measured by the Panic Disorder Severity Scale , Body Sensation Question naire , and Agoraphobic Cognitions Question naires . Significant reductions were also reported on measures of disability and depression . The mean within- and between-group effect size ( Cohen 's d ) on the Panic Disorder Severity Scale was 0.93 and 0.59 , respectively , and effects were sustained at 1-month follow-up . Mean therapist time per participant was 75 minutes for the program . Conclusions : These results replicate those from the open trial of the Panic Program indicating the efficacy of the Internet-based clinician-assisted cognitive behavioural treatment program for panic disorder with agoraphobia BACKGROUND AND OBJECTIVE Publication bias and other sample size effects are issues for meta-analyses of test accuracy , as for r and omized trials . We investigate limitations of st and ard funnel plots and tests when applied to meta-analyses of test accuracy and look for improved methods . METHODS Type I and type II error rates for existing and alternative tests of sample size effects were estimated and compared in simulated meta-analyses of test accuracy . RESULTS Type I error rates for the Begg , Egger , and Macaskill tests are inflated for typical diagnostic odds ratios ( DOR ) , when disease prevalence differs from 50 % and when thresholds favor sensitivity over specificity or vice versa . Regression and correlation tests based on functions of effective sample size are valid , if occasionally conservative , tests for sample size effects . Empirical evidence suggests that they have adequate power to be useful tests . When DORs are heterogeneous , however , all tests of funnel plot asymmetry have low power . CONCLUSION Existing tests that use st and ard errors of odds ratios are likely to be seriously misleading if applied to meta-analyses of test accuracy . The effective sample size funnel plot and associated regression test of asymmetry should be used to detect publication bias and other sample size related effects Eighty-four chronic phobic patients were r and omly assigned to self-exposure in vivo instructed by either a psychiatrist , a computer or a book ; mean therapy time per patient was respectively 3.1 , 3.2 and 0 hours . Seventy-one patients completed treatment . All three groups improved substantially and similarly to 6 months follow-up , with no significant difference between them ; self-exposure treatment was effective even without therapist contact . Among the three groups , initial expectation of help and positive attitude to the psychiatrist were equally high and related to subsequent rating of help received . All three groups rated the psychiatrist as more tolerant , reliable , and underst and ing than the computer or book , but these attitudes did not relate to outcome , were initially similar among all three groups , and changed minimally at 6 months follow-up OBJECTIVE The authors sought to observe the long-term clinical course of anxiety disorders over 12 years and to examine the influence of comorbid psychiatric disorders on recovery from or recurrence of panic disorder , generalized anxiety disorder , and social phobia . METHOD Data were drawn from the Harvard/Brown Anxiety Disorders Research Program , a prospect i ve , naturalistic , longitudinal , multicenter study of adults with a current or past history of anxiety disorders . Probabilities of recovery and recurrence were calculated by using st and ard survival analysis methods . Proportional hazards regression analyses with time-varying covariates were conducted to determine risk ratios for possible comorbid psychiatric predictors of recovery and recurrence . RESULTS Survival analyses revealed an overall chronic course for the majority of the anxiety disorders . Social phobia had the smallest probability of recovery after 12 years of follow-up . Moreover , patients who had prospect ively observed recovery from their intake anxiety disorder had a high probability of recurrence over the follow-up period . The overall clinical course was worsened by several comorbid psychiatric conditions , including major depression and alcohol and other substance use disorders , and by comorbidity of generalized anxiety disorder and panic disorder with agoraphobia . CONCLUSIONS These data depict the anxiety disorders as insidious , with a chronic clinical course , low rates of recovery , and relatively high probabilities of recurrence . The presence of particular comorbid psychiatric disorders significantly lowered the likelihood of recovery from anxiety disorders and increased the likelihood of their recurrence . The findings add to the underst and ing of the nosology and treatment of these disorders Sixty-four individuals with social phobia ( social anxiety disorder ) were assigned to a multimodal cognitive-behavioral treatment package or to a waiting list control group . Treatment consisted of a 9-week , Internet-delivered , self-help program that was combined with 2 group exposure sessions in real life and minimal therapist contact via e-mail . Results were analyzed on an intention-to-treat basis , including all r and omized participants . From pre- to posttest , treated participants in contrast to controls showed significant improvement on most measured dimensions ( social anxiety scales , general anxiety and depression levels , quality of life ) . The overall within- and between-groups effect sizes were Cohen 's d = 0.87 and 0.70 , respectively . Treatment gains were maintained at 1-year follow-up . The results from this study support the continued use and development of Internet-distributed , self-help programs for people diagnosed with social phobia This paper describes a long‐term follow‐up of patients with panic disorder who received cognitive behaviour therapy within a r and omized controlled trial . Of 89 patients eligible for follow‐up , 28 ( 31.5 % ) were reassessed 6–8 years after commencement of treatment in the trial . No differences were found between those who were followed up and those lost to follow‐up on most baseline measures including measures of panic‐related psychopathology , or depression . Outcomes at long‐term follow‐up were significantly better than baseline measures of panic , avoidance and depression . In this sub‐ sample the effect of cognitive behaviour therapy for panic disorder appears to maintain over the long‐term BACKGROUND Non-professional treatment programmes are presumed to relieve the extensive need for care of anxiety and depression disorders . This study investigates the effectiveness of cognitive self- therapy ( CST ) in the treatment of depression or generalized anxiety disorder . METHOD Patients ( n=151 ) were r and omized to receive CST or treatment as usual ( TAU ) in a trial lasting for 18 months , measuring symptoms ( SCL-90 ; main outcome ) , social functions , quality of life and utilization of care . RESULTS Patients in both conditions improved significantly , but no difference was found between the conditions . Reduction of symptoms , improvement of social functions and medical utilization were maintained at the end of the 18 months . Medical care utilization ( therapist contact and hospitalization ) was lower for CST than for TAU . No suicides occurred . CONCLUSIONS Cognitive self-therapy is likely to decrease the need for care of chronic depression and anxiety disorders , but it has not been proven to be more effective than treatment as usual Cognitive-behavioral therapy incorporating exposure and response prevention ( ERP ) is widely considered a first-line psychosocial treatment for patients with obsessive-compulsive disorder ( OCD ) . However , a number of obstacles prevent many patients from receiving this treatment , and self-administered ERP may be a useful alternative or adjunct . Forty-one adult out patients with a primary diagnosis of OCD , who reported at least 1 current or previous adequate medication trial , were r and omly assigned to self-administered or therapist-administered ERP . Patients in both treatment conditions showed statistically and clinical ly significant symptom reduction . However , patients receiving therapist-administered ERP showed a superior response in terms of OCD symptoms and self-reported functional impairment . We discuss several potential reasons for the superiority of therapist-administered treatment , and propose a stepped-care integration of self-administered and therapist-administered interventions for OCD Two hundred and ten psychiatric patients with one of three DSM-III diagnoses , generalized anxiety disorder ( N = 71 ) , panic disorder ( N = 74 ) or dysthymic disorder ( N = 65 ) , were included in a clinical trial in which diazepam , dothiepin or placebo tablets , cognitive and behaviour therapy , or a self-help package were given over ten weeks . Personality status was assessed independently using a structured interview , the Personality Assessment Schedule . One hundred and ninety-eight patients had personality assessment s , 89 % with a close informant . Thirty-six per cent had a personality disorder and these patients had more severe psychopathology than those with no personality disorder . Personality disorder was more common in patients with dysthymic disorder and this group responded less well to treatment . The category of personality disorder had no apparent influence on symptoms Assessing the quality of r and omized controlled trials ( RCTs ) is important and relatively new . Quality gives us an estimate of the likelihood that the results are a valid estimate of the truth . We present an annotated bibliography of scales and checklists developed to assess quality . Twenty-five scales and nine checklists have been developed to assess quality . The checklists are most useful in providing investigators with guidelines as to what information should be included in reporting RCTs . The scales give readers a quantitative index of the likelihood that the reported methodology and results are free of bias . There are several shortcomings with these scales . Future scale development is likely to be most beneficial if questions common to all trials are assessed , if the scale is easy to use , and if it is developed with sufficient rigor The Cross-National Collaborative Panic Study is a two-phase multinational , multicenter controlled trial for the evaluation of drug treatment of panic disorder and associated agoraphobia . The First Phase compared alprazolam with placebo in a large sample of more than 600 subjects at eight centers -- five in the United States , two in Canada , and one in Australia . The Second Phase compared alprazolam , imipramine hydrochloride , placebo in more than 1100 patients in 14 countries . The scientific background , aims and purpose s , governance , and policies regarding statistical analyses and scientific presentations and publications are review ed as background for the series of individual articles reporting detailed findings from the First Phase Abstract The results of a five month follow-up study on an automated group systematic desensitization treatment for test anxiety are reported . The study focuses on data relevant to:(1 ) the relative permanency of the automated group technique ; ( 2 ) comparison of the longer-term effect of the therapist 's presence vs. his absence on outcome ; ( 3 ) the issue of symptom substitution . The follow-up data indicate that the initial improvement following the automated treatment technique is not only maintained , but that further gains are also evident . The presence vs. absence of the therapist does make a significant difference in the amount of improvement found at the follow-up . And , finally , 85 per cent of the desensitized , S s did not experience side effects The aim of this study was to assess the effects of a 7‐week st and ardized cognitive behavioural treatment of work‐related stress conducted via e‐mail . A total of 342 people applied for treatment in reaction to a newspaper article . Initial screening reduced the sample to a heterogeneous ( sub ) clinical group of 239 participants . Participants were assigned r and omly to a waiting list condition ( n = 62 ) , or to immediate treatment ( n = 177 ) . A follow‐up was conducted 3 years after inception of the treatment . The outcome measures used were the Depression Anxiety Stress Scales ( DASS‐42 ) and the Emotional Exhaustion scale of the Maslach Burnout Inventory – General Survey ( MBI‐GS ) . Fifty participants ( 21 % ) dropped out . Both groups showed statistically significant improvements . Intention‐to‐treat analysis of covariance ( ANCOVAs ) revealed that participants in the treatment condition improved significantly more than those in the waiting control condition ( 0.001<p⩽0.025 ) . In the treatment group , the effects were large to moderate ( 0.9 (stress)⩾d⩾0.5 ( anxiety ) ) . The between‐group effects ranged from d = 0.6 ( stress ) to d = 0.1 ( anxiety ) . At follow‐up , the effects were more pronounced , but this result requires replication in view of high attrition at follow‐up . The results warrant further research on Internet‐driven st and ardized cognitive behavioural therapy for work‐related stress . Such research should include the direct comparison of this treatment with face‐to‐face treatment , and should address the optimal level of therapist contact in Internet‐driven treatment R and omized controlled trials of public health interventions are often complex : practitioners may not deliver interventions as research ers intended , participants may not initiate interventions and may not behave as expected , and interventions and their effects may vary with environmental and social context . Reports of r and omized controlled trials can be misleading when they omit information about the implementation of interventions , yet such data are frequently absent in trial reports , even in journals that endorse current reporting guidelines . Particularly for complex interventions , the Consoli date d St and ards of Reporting Trials ( CONSORT ) statement does not include all types of information needed to underst and the results of r and omized controlled trials . CONSORT should be exp and ed to include more information about the implementation of interventions in all trial arms It has been suggested that maintenance treatment of patients who have remitted panic disorder with agoraphobia beyond the six months of acute phase imipramine treatment may decrease the risk of relapse . This study further explores the relationship between relapse and duration of imipramine treatment in this population . Fifty-one patients , all in remission at the end of six months acute phase open trial with imipramine 2.25 mg/kg/day and r and omized to double-blind maintenance or placebo substitution , discontinued imipramine treatment eventually and were followed over a 12-month risk period : 27 during first year placebo substitution , 7 after 12 months of imipramine maintenance in placebo substitution , and 17 after variable duration s of imipramine maintenance in open discontinuation . There were no behaviorally oriented interventions or instructions at any time during the acute and maintenance phases of treatment or during imipramine discontinuation . Duration of imipramine treatment , the method of discontinuation ( open versus placebo substitution ) , or any of the 9 variables from the demographic , clinical , and open treatment domains that were entered in a Cox proportional hazard model did not predict relapse . The rate of relapse after only 6 months of treatment ( 10 out of 27 , 37 % ) was identical to the rate of relapse after 12 to 30 months of treatment ( 9 out of 24 , 37.5 % ) . The results suggest a lack of specific protective effects beyond prophylaxis and underscore the difficulty in predicting relapse in fully remitted panic disorder with agoraphobia patients . Early detection of relapse in patients who discontinue treatment may be a viable alternative to prediction CONTEXT Panic disorder ( PD ) may be treated with drugs , psychosocial intervention , or both , but the relative and combined efficacies have not been evaluated in an unbiased fashion . OBJECTIVE To evaluate whether drug and psychosocial therapies for PD are each more effective than placebo , whether one treatment is more effective than the other , and whether combined therapy is more effective than either therapy alone . DESIGN AND SETTING R and omized , double-blind , placebo-controlled clinical trial conducted in 4 anxiety research clinics from May 1991 to April 1998 . PATIENTS A total of 312 patients with PD were included in the analysis . INTERVENTIONS Patients were r and omly assigned to receive imipramine , up to 300 mg/d , only ( n=83 ) ; cognitive-behavioral therapy ( CBT ) only ( n=77 ) ; placebo only ( n=24 ) ; CBT plus imipramine ( n=65 ) ; or CBT plus placebo ( n=63 ) . Patients were treated weekly for 3 months ( acute phase ) ; responders were then seen monthly for 6 months ( maintenance phase ) and then followed up for 6 months after treatment discontinuation . MAIN OUTCOME MEASURES Treatment response based on the Panic Disorder Severity Scale ( PDSS ) and the Clinical Global Impression Scale ( CGI ) by treatment group . RESULTS Both imipramine and CBT were significantly superior to placebo for the acute treatment phase as assessed by the PDSS ( response rates for the intent-to-treat [ ITT ] analysis , 45.8 % , 48.7 % , and 21.7 % ; P=.05 and P=.03 , respectively ) , but were not significantly different for the CGI ( 48 . 2 % , 53.9 % , and 37.5 % , respectively ) . After 6 months of maintenance , imipramine and CBT were significantly more effective than placebo for both the PDSS ( response rates , 37.8 % , 39.5 % , and 13.0 % , respectively ; P=.02 for both ) and the CGI ( 37.8 % , 42.1 % , and 13.0 % , respectively ) . Among responders , imipramine produced a response of higher quality . The acute response rate for the combined treatment was 60.3 % for the PDSS and 64.1 % for the CGI ; neither was significantly different from the other groups . The 6-month maintenance response rate for combined therapy was 57.1 % for the PDSS ( P=.04 vs CBT alone and P=.03 vs imipramine alone ) and 56.3 % for the CGI ( P=.03 vs imipramine alone ) , but not significantly better than CBT plus placebo in either analysis . Six months after treatment discontinuation , in the ITT analysis CGI response rates were 41.0 % for CBT plus placebo , 31.9 % for CBT alone , 19.7 % for imipramine alone , 13 % for placebo , and 26.3 % for CBT combined with imipramine . CONCLUSIONS Combining imipramine and CBT appeared to confer limited advantage acutely but more substantial advantage by the end of maintenance . Each treatment worked well immediately following treatment and during maintenance ; CBT appeared durable in follow-up . JAMA . 2000;283:2529 - BACKGROUND There are significant barriers to accessing effective psychological therapy in primary care result ing from a lack of suitably trained therapists to meet current dem and . More efficient service delivery using minimal interventions ( such as bibliotherapy ) provided by paraprofessional therapists may be one method of overcoming these problems , and is the subject of attention in the UK and elsewhere . A r and omized trial was conducted to test the clinical effectiveness of this model . Assistant psychologists delivered a guided self-help intervention to patients with anxiety and depression who were currently waiting for psychological therapy . METHOD A total of 114 patients were r and omized either to guided self-help or a waiting-list control group . All patients were followed up 3 months later , prior to starting conventional psychological therapy . Measures included self-reported adherence to the intervention , anxiety and depressive symptoms , social functioning and patient satisfaction . RESULTS Adherence to the guided self-help intervention was acceptable and patients reported satisfaction with the intervention . However , there were no statistically significant differences between groups in anxiety and depression symptoms at 3 months . CONCLUSIONS The results demonstrate that this model of guided self-help did not provide additional benefit to patients on a waiting list for psychological therapy . The results are considered in the context of possible internal and external validity threats , and compared with previous trials of minimal interventions . The implication s of the results for the design of future minimal interventions are considered This study investigated the effects of an internet-based self-help stress management program with a r and omized controlled design . Of 85 participants , 26 % dropped out , leaving a final sample of 63 participants with 23 in the treatment group and 40 in the waiting list control group . Treatment included applied relaxation , problem solving , time management and cognitive restructuring . All information and treatment interventions were provided via the internet . Results were evaluated with the Perceived Stress Scale and the Hospital Anxiety and Depression Scale . Improvements were seen in both groups , with greater improvements in the self-help treatment group . It is concluded that the internet can be used to provide stress management techniques and result in stress relief . However , spontaneous improvement , differential dropout rate and compliance need to be monitored in future studies A controlled trial study which examined the clinical effectiveness of a stress self-help package administered by general practitioners to patients presenting with psychological problems which were potentially stress-related is described . Patients were r and omly allocated to one of two groups : existing general practitioner treatment with or without the use of the package . Significant advantages were found for patients who received the package compared with controls in both their level of symptoms at three-month follow-up and their rate of consulting for psychological problems in the three-month post-treatment period compared with the three-month pre-treatment period . The potential use of such packages in the treatment of psychological problems in primary care is discussed Evidence is growing that two modalities of computer-based exposure therapies — virtual reality and computer-aided psychotherapy — are effective in treating anxiety disorders , including fear of flying . However , they have not yet been directly compared . The aim of this study was to analyze the efficacy of three computer-based exposure treatments for fear of flying : virtual reality exposure therapy ( VRET ) , computer-aided exposure with a therapist ’s ( CAE-T ) assistance throughout exposure sessions , and self-administered computer-aided exposure ( CAE-SA ) . A total of 60 participants with flying phobia were r and omly assigned to VRET , CAE-T , or CAE-SA . Results indicate that the three interventions were effective in reducing fear of flying at posttreatment and at 1-year follow-up ; furthermore , there were no significant differences between them in any of the outcome measure . Large within-group effect sizes were found for all three treatment conditions at both posttreatment and at follow-up . The results suggest that therapist involvement might be minimized during computer-based treatments and that CAE can be as effective as VRET in reducing fear of flying Repeated assessment s of psychopathology , together with personality status , were made over two years on 181 psychiatric out- patients with generalised anxiety disorder ( 59 ) , panic disorder ( 66 ) , or dysthymic disorder ( 56 ) diagnosed using an interview schedule for DSM-III . Patients were r and omly allocated to drug treatment , cognitive and behaviour therapy , or a self-help treatment programme . Although there were no overall differences in compliance rate and efficacy between the three modes of treatment , the psychological treatment methods , particularly self-help , were more effective in patients without personality disorder , and those with personality disorder responded better to drug treatment , primarily antidepressants . The findings suggest that assessment of personality status could be a valuable aid to selection of treatment in neurotic disorders and that self-help approaches are particularly valuable once personality disorder has been excluded The aim of our study was to evaluate the effectiveness of a self‐information booklet ( SIB ) in decreasing anxiety and panic attacks in Panic Disorder ( PD ) patients . Eighty‐four patients attending an outpatient clinic due to panic disorder were r and omly chosen to receive paroxetine with/without a friendly‐ design ed brochure . Follow‐up was done by a masked rater after 1 , 3 , and 12 weeks in order to evaluate whether the co‐administration of paroxetine and the brochure ( Group A ) had a beneficial effect over the administration of paroxetine alone ( Group B ) . After 3 weeks of therapy , Group A patients had significantly greater improvement and lower scores on the Hamilton Anxiety Scale , the Panic Self Question naire , and the Visual Analog Scale . After 12 weeks , the differential improvement was not statistically significant and both groups had improved as compared to baseline . The administration of a psychoeducational brochure ( SIB ) to PD patients at the initiation of therapy had beneficial effects during the first weeks of treatment . Although this effect fades away , the role of the SIB is overstressed in its ability to increase well being and compliance , and reduce anxiety and panic attacks . Depression and Anxiety 16:71–76 , 2002 . © 2002 Wiley‐Liss , Fifty-two patients with spider phobia , fulfilling the DSM-III-R criteria for simple phobia , were assessed with behavioral , physiological and self-report measures . They were r and omly assigned to five different treatment conditions : ( 1 ) one session therapist-directed exposure ( maximum 3 hours ) , ( 2 ) specific manual-based treatment in the home , ( 3 ) specific manual-based treatment at the clinic , ( 4 ) general manual-based treatment in the home and ( 5 ) general manual-based treatment at the clinic . The results show that therapist-directed one-session treatment was significantly more effective than three of the manual-based treatments , both at the post-treatment and follow-up stages . Specific manual-based treatment at the clinic was significantly more successful than the other manual-based treatments , but only at follow-up . The proportion of clinical ly significant improved patients at follow-up was 80 % in the therapist-directed group compared to 63 % for the specific manual-based treatment at the clinic , 10 % for specific manual-based treatment in the home , 9 % for general manual-based treatment in the home , and 10 % for general manual-based treatment at the clinic . The conclusion that can be drawn is that one-session therapist-directed treatment is the treatment of choice for spider phobia but manual-based treatment is a good alternative in some cases BACKGROUND Self-administered cognitive behavior therapy ( SCBT ) has been shown to be an effective alternative to therapist-delivered treatment for panic disorder ( PD ) . However , it is unknown whether combining SCBT and antidepressants can improve treatment . This trial evaluated the efficacy of SCBT and sertraline , alone or in combination , in PD . METHOD Patients ( n=251 ) were r and omized to 12 weeks of either placebo drug , placebo drug plus SCBT , sertraline , or sertraline plus SCBT . Those who improved after 12 weeks of acute treatment received treatment for an additional 12 weeks . Outcome measures included core PD symptoms ( panic attacks , anticipatory anxiety , agoraphobic avoidance ) , dysfunctional cognitions ( fear of bodily sensations , agoraphobic cognitions ) , disability , and clinical global impression of severity and improvement . Efficacy data were analyzed using general and generalized linear mixed models . RESULTS Primary analyses of trends over time revealed that sertraline/SCBT produced a significantly greater rate of decline in fear of bodily sensations compared to sertraline , placebo/SCBT and placebo . Trends in other outcomes were not significantly different over time . Secondary analyses of mean scores at week 12 revealed that sertraline/SCBT fared better on several outcomes than placebo , with improvement being maintained at the end of continuation treatment . Outcome did not differ between placebo and either sertraline monotherapy or placebo/SCBT . Moreover , few differences emerged between the active interventions . CONCLUSIONS This trial suggests that sertraline combined with SCBT may be an effective treatment for PD . The study could not confirm the efficacy of sertraline monotherapy or SCBT without concomitant medication or therapist assistance in the treatment of PD Spider phobic subjects ( n = 45 ) completed 3 x 40 minute computer-delivered treatment sessions . Question naire ratings of phobic severity were completed pre- and posttreatment ( n = 45 ) and 6 - 12 month follow-up ( n = 38 ) . The program used interactive animations to model self-exposure treatment methods . Subjects were r and omized to one of three treatment groups ( n = 15 ) , each receiving a different version of the program . These treatment conditions were relevant exposure with feedback ( REF ) , relevant exposure with no feedback ( RENoF ) , or irrelevant exposure with feedback ( IEF ) . Relevant exposure modeled exposure to spiders , irrelevant exposure to elevators . All groups showed significant phobic improvement following the treatment , as measured on a variety of instruments . Learning on the programs was demonstrated by a significantly increased performance ( time taken to reach a target score ) within each group across the three computer treatment sessions . Outcome was not significantly affected either relevance of exposure or the manipulation of the onscreen feedback . Subjects ' report of exposure treatment undertaken at home correlated positively with phobic improvement Objective : To compare the effectiveness of Internet cognitive behaviour therapy ( CBT ) with face-to-face CBT in social phobia . Methods : R and omized controlled trial of 75 patients with social phobia referred to an anxiety disorders clinic . A total of 37 patients participated , and post-treatment data was obtained from 25 Subjects ( Ss ) . An intention to treat analysis was used . The same therapist ( M.D. ) treated both groups . Results : Both groups made significant progress on symptoms and disability measures . There were no significant differences in outcome between the Internet and face-to-face groups . The total amount of therapist time required was 18 min per patient for the Internet group and 240 min per patient for the face-to-face group . Conclusions : Both forms of treatment were equally effective and this is consistent with previous findings in depression and panic disorder . The difference in clinician time required was substantial . If Internet CBT was offered as ‘ st and ard of care ’ the staff time saved would permit a stepped care model in which in-depth therapy for the difficult to recover patients could be provided without an increase in staff Discussed is the impact of a videotaped dental fear-reduction program on moderately and highly fearful people who avoid dental treatment . Subjects were assigned r and omly to one of two groups -- the videotaped treatment group or the videotaped placebo group . The results indicate that the videotaped treatment program produced a decrease in self-reported fear in both moderately fearful and highly fearful subjects . However , the treatment program increased dental visitation and appointment-making behavior only for moderately fearful subjects Social anxiety disorder ( SAD ) is highly prevalent and associated with a substantial societal economic burden , primarily due to high costs of productivity loss . Cognitive behavior group therapy ( CBGT ) is an effective treatment for SAD and the most established in clinical practice . Internet-based cognitive behavior therapy ( ICBT ) has demonstrated efficacy in several trials in recent years . No study has however investigated the cost-effectiveness of ICBT compared to CBGT from a societal perspective , i.e. an analysis where both direct and indirect costs are included . The aim of the present study was to investigate the cost-effectiveness of ICBT compared to CBGT from a societal perspective using a prospect i ve design . We conducted a r and omized controlled trial where participants with SAD were r and omized to ICBT ( n=64 ) or CBGT ( n=62 ) . Economic data were assessed at pre-treatment , immediately following treatment and six months after treatment . Results showed that the gross total costs were significantly reduced at six-month follow-up , compared to pre-treatment in both treatment conditions . As both treatments were equivalent in reducing social anxiety and gross total costs , ICBT was more cost-effective due to lower intervention costs . We conclude that ICBT can be more cost-effective than CBGT in the treatment of SAD and that both treatments reduce societal costs for SAD Over the past five years several studies have suggested that flooding and its analogues reduce fear in animals and in man . The literature on analogues of flooding in animals was surveyed by Baum ( 1970 ) , who himself demonstrated that prevention of a conditioned avoidance response in rats extinguishes the response ( Baum , 1966 ) . The longer the duration of response prevention , the quicker the extinction of the avoidance response ( Baum , 1969a ) . The greater the shock trauma involved in the original learning of the response , the longer the response prevention had to be before the avoidance response was extinguished ( Baum , 1969b , 1970 ) . In phobic human volunteers controlled studies showed that flooding in imagination reduced avoidance responses to rats ( Hogan and Kirchner , 1967 , 1968 ; Kirchner and Hogan , 1966 ) , and that the technique worked more quickly than desensitization ( Barrett , 1969 ) in improving snake phobias . An analogue of flooding — exposure in real life with response prevention — was also shown to be more effective than desensitization for the reduction of snake phobias ( Strahley , 1965 ) . Two studies found , however , that desensitization was superior to flooding for the reduction of snake phobias ( Mealiea , 1967 ) and mouse phobias ( Willis and Edwards , 1969 ) , while in a further two reports flooding was not significantly different in effectiveness from desensitization for the reduction of snake phobias ( de Moor , 1970 ) or stage fright ( Calef and Maclean , 1970 ) Phobia/panic disorder is common . It improves with exposure therapy , even when guided mainly by a computer self‐help system such as FearFighter ( FF ) , but such therapy must also demonstrate cost‐effectiveness . This study compares the cost‐effectiveness of FF with computed‐aided relaxation and clinician‐led exposure . Data were obtained on patients from a r and omised controlled trial of FF . Economic analyses used pretreatment and 1‐month follow‐up self‐ratings of the main problem and global phobia . Clinician costs were calculated using the number of therapist hours and the cost of FF . Incremental cost‐effectiveness ratios were calculated and cost‐effectiveness acceptability curves were produced . Data were available on 62 patients with main problem ratings and 60 with global phobia ratings . FF and clinician‐led exposure were more effective than relaxation but more expensive . Compared with relaxation , producing an extra unit of improvement on the main problem scale cost £ 64 with FF and £ 100 with clinician‐led exposure . FF appeared to be more cost‐effective using the global phobia rating ( £ 112 per extra unit of improvement vs. £ 128 for clinician‐led exposure ) . The cost‐effectiveness of FF could be enhanced if users had less highly trained supporters . FF would be less cost‐effective if face‐to‐face therapy was delivered by less qualified professionals . Caution is urged regarding these indicative findings given that these were secondary analyses BACKGROUND Emotional distress has major implication s for employees and employers . Cognitive behavioural therapy ( CBT ) is a recommended treatment , but dem and outstrips supply . CBT is well suited to computerization . Most employee assistance programmes have not been systematic ally evaluated and computerized CBT has not previously been studied in the workplace . AIMS To evaluate the effect of an 8 week computerized cognitive behavioural therapy programme , ' Beating The Blues ' , on emotional distress in employees with recent stress-related absenteeism , and to explore the reasons for non-participation . METHODS An open , r and omized trial in a London NHS occupational health department . Forty-eight public sector employees , with 10 or more cumulative days stress-related absenteeism in the last 6 months , r and omized equally to ' Beating The Blues ' plus conventional care , or conventional care alone . Main outcome measures were Hospital Anxiety and Depression Scale and Attributional Style Question naire scores at end of treatment and 1 , 3 and 6 months later ; and reasons for non-participation . RESULTS At end of treatment and 1 month later , adjusted mean depression scores and adjusted mean negative attributional style scores were significantly lower in the intervention group . One month post-treatment , adjusted mean anxiety scores were also significantly lower in the intervention group . The differences were not statistically significant at 3 and 6 months post-treatment . Non-participation was common and related to access problems , preference for other treatments , time commitment , scepticism about the intervention and the employer connection . CONCLUSIONS ' Beating The Blues ' may accelerate psychological recovery in employees with recent stress-related absenteeism . Greater flexibility and accessibility might improve uptake Abstract Eighteen S s received tape-recorded desensitization along a st and ardized mouse approach hierarchy . Nine of these S s had been previously allowed to govern their rates of progress during two sessions of semi-automated relaxation training . The other 9 S s received two sessions of totally st and ardized relaxation training . The efficacy of desensitization for the two groups was compared and evaluated relative to the performance of two control groups . Implication s for future research are discussed The last decade has witnessed remarkable progress in the treatment of obsessive-compulsives , with the introduction of response prevention and deliberate exposure to feared situations in vivo and in imagination . In a series of studies , the effects of the single components of this program were investigated . The results suggest that the optimal treatment includes a combination of all three procedures . It appears that in vivo exposure mainly affects anxiety/discomfort associated with cues for ritualizing ; response prevention affects primarily compulsive behavior ; and imaginal exposure assists in maintenance of treatment gains , perhaps through its impact on fears of future catastrophes associated with obsessions The results of applied relaxation training in patients with generalised anxiety and panic attacks are reported . ART was taught during one session , by means of participant demonstration , written instructions , taped instructions , or a combination of all three , with instructions to practice at home . All four methods proved superior to a waiting list control , but there were no differences between the treatment groups . There was some evidence for the non-specific effect of expectancy , but this did not completely explain the treatment effect Abstract Thirty co-eds with ascertained fears of snakes were exposed to an implosive , eclectic verbal or bibliotherapy session . Ten Ss were in each group . For a S to be judged a success at the conclusion of the session , she had to pick up a 3 1 2 ft king snake . There were significant differences ( 0.05 level ) between Ss who had implosive therapy and those who had bibliotherapy on the post test . No significant differences were found between the implosive and eclectic verbal Ss on this post test . Subjects who failed to pick up the snake were subsequently imploded . 66.66 Per cent of them later lifted up the animal . Results of this study were compared with those of previous research on implosion Internet‐based interventions with therapist support have proven effective for treating a range of mental health conditions . This study examined whether frequency of therapist contact affected treatment outcomes . Fifty‐seven people with panic disorder ( including 32 with agoraphobia ) were r and omly allocated to an 8‐week Internet‐based cognitive behavioural treatment intervention ( Panic Online ) with either frequent ( three e‐mails per week ) or infrequent ( one e‐mail per week ) support from a psychologist . Posttreatment , intention‐to‐treat analyses revealed that both treatments were effective at improving panic disorder and agoraphobia severity ratings , panic‐related cognitions , negative affect , and psychological and physical quality of life domains , with no differences between conditions . High end‐state functioning was achieved by 28.6 % of the frequent and infrequent participants , respectively . Therapist alliance , treatment credibility , and satisfaction also did not differ between groups , despite significantly greater therapist time invested in the frequent contact condition . The results provide evidence that the effectiveness of Internet‐based mental health interventions may be independent of the frequency of therapist support and may , therefore , be more cost‐effective than previously reported BACKGROUND Hypochondriasis , characterised by severe health anxiety , is a common condition associated with functional disability . Cognitive-behavioural therapy ( CBT ) is an effective but not widely disseminated treatment for hypochondriasis . Internet-based CBT , including guidance in the form of minimal therapist contact via email , could be a more accessible treatment , but no study has investigated internet-based CBT for hypochondriasis . AIMS To investigate the efficacy of internet-based CBT for hypochondriasis . METHOD A r and omised controlled superiority trial with masked assessment comparing internet-based CBT ( n = 40 ) over 12 weeks with an attention control condition ( n = 41 ) for people with hypochondriasis . The primary outcome measure was the Health Anxiety Inventory . This trial is registrated with Clinical Trials.gov ( NCT00828152 ) . RESULTS Participants receiving internet-based CBT made large and superior improvements compared with the control group on measures of health anxiety ( between-group Cohen 's d range 1.52 - 1.62 ) . CONCLUSIONS Internet-based CBT is an efficacious treatment for hypochondriasis that has the potential to increase accessibility and availability of CBT for hypochodriasis Cognitive-behavioral therapy ( CBT ) is the psychological treatment of choice for panic disorder ( PD ) . However , given limited access to CBT , it must be delivered with maximal cost-effectiveness . Previous research ers have found that a brief computer-augmented CBT was as effective as extended therapist-delivered CBT . To test this finding , this study r and omly allocated 186 patients with PD across 2 sites in Scotl and and Australia to 12 sessions of therapist-delivered CBT ( CBT12 ) , 6 sessions of therapist-delivered ( CBT6 ) or computer-augmented CBT ( CBT6-CA ) , or a waitlist control . On a composite measure , at posttreatment , the outcome for CBT 12 was statistically better than the outcome for CBT6 . The outcome for CBT6-CA fell between CBT12 and CBT6 , but could not be statistically distinguished from either treatment . The active treatments did not differ statistically at 6-month follow-up . The study provided some support for the use of computers as an innovative adjunctive-therapy tool and merits further investigation Abstract The present study was an attempt to develop an automated ( i.e. preprogrammed and mechanically administered ) group desensitization treatment for test anxiety : to evaluate the effectiveness of the treatment of systematic desensitization without counseling ; and to determine the importance of the physical presence or absence of the therapist in the sessions . Forty-two test-anxious female college students were divided into three matched groups on the basis of previous semesters ' grade point average ( G.P.A. ) . The three groups consisted of a Waiting List control and two treatment groups ; in one group , desensitization was administered by a therapist , whereas in the other , by a tape recorded set of instructions . Both treatment groups manifested a significant improvement in the G.P.A. following treatment , when compared with the control group . In addition , self-report measures indicated that following final exams there was a significant reduction of daily anxiety for treatment groups as compared to the controls . No significant differences were found when the two treatments were compared with each other ; however , a strong trend favoring the Therapist-Present group was noted for improved In the present study , the authors sought to determine whether the efficiency and cost-effectiveness of cognitive-behavioral treatment ( CBT ) for panic disorder could be improved by adjunctive computer-assisted therapy . Eighteen participants who met Diagnostic and Statistical Manual of Mental Disorders ( 3rd ed . , revised ; American Psychiatric Association , 1987 ) criteria for panic disorder were r and omly assigned to a 12-session CBT ( CBT 12 ) condition ( D. H. Barlow & M. G. Craske , 1989 ) or to a 4-session computer-assisted CBT ( CBT4-CA ) condition . Palmtop computers , with a program developed to incorporate basic principles of CBT , were used by CBT4-CA clients whenever they felt anxious or wanted to practice the therapy techniques and were used by all participants as a momentary assessment tool . CBT4-CA clients carried the computer at all times and continued to use it for 8 weeks after termination of therapy . Analyses of clinical ly significant changes showed superiority of CBT12 at posttest on some measures ; however , there were no differences at follow-up Treatment-resistant obsessive-compulsive disorder ( OCD ) patients from around the United Kingdom who employed computer-guided self-help by using BTSteps over 17 weeks were r and omized to have brief live phone support from a clinician either ( 1 ) in nine Scheduled clinician-initiated calls or ( 2 ) only in calls Requested by the patient ( n=22 per condition ) . Call content and mean duration were similar across conditions . Scheduled-support patients dropped out significantly less often , did more homework of self-exposure and self-imposed ritual prevention ( 95 % vs. 57 % ) , and showed more improvement in OCD symptoms and disability . Mean total support time per patient over 17 weeks was 76 minutes for Scheduled and 16 minutes for Requested patients . Giving brief support proactively by phone enhanced OCD patients ' completion of and improvement with computer-aided self-help Preliminary reports of discontinuation of alprazolam therapy in patients with panic disorder have revealed worsening of symptoms despite gradual withdrawal of medication . In this study , 126 patients with panic disorder and phobic avoidance received either alprazolam or placebo in doses of 2 to 10 mg daily for eight weeks . The medication was tapered over a period of four weeks , and patients were observed for another two weeks after all medication was discontinued . Sixty of the 63 alprazolam-treated patients and 49 of the 63 placebo-treated patients entered the taper and discontinuation study . After improvement in the active treatment period , the alprazolam-treated group had significant relapse between the first and last week of taper . However , during the second postdiscontinuation week , outcome scores were not significantly different from those of the placebo-treated group who did not deteriorate during taper . Twenty-seven percent of the alprazolam-treated group reported a rebound of panic attacks during taper and 13 % reported a rebound of anxiety on the Hamilton Anxiety Scale . No serious or life-threatening withdrawal symptoms were reported , but distinct , transient , mild to moderate withdrawal syndrome occurred in 35 % of the alprazolam-treated group and in none of the placebo-treated group . The coexistence of symptom rebound and a withdrawal syndrome occurred in 10 % of the alprazolam-treated group , but both subsided by the end of the second week without alprazolam . We recommend that patients with panic disorder be treated for a longer period , at least six months , and that medication be tapered over a more prolonged period , at least eight weeks , especially where high doses are employed 210 psychiatric out patients with generalised anxiety disorder ( 71 ) , or panic disorder ( 74 ) , or dysthymic disorder ( 65 ) diagnosed by an interview schedule for DSM-III were allocated by constrained r and omisation to one of five treatments : diazepam ( 28 ) , dothiepin ( 28 ) , placebo ( 28 ) , cognitive and behaviour therapy ( 84 ) , and a self-help treatment programme ( 42 ) . All treatments were given for 6 weeks and then withdrawn by 10 weeks . Ratings of psychopathology were made by psychiatric assessors blind to both treatment and diagnosis before treatment and at 2 , 4 , 6 , and 10 weeks after r and omisation . 18 patients had insufficient data for analysis because of early drop-out . There were no important differences in treatment response between the diagnostic groups , but diazepam was less effective than dothiepin , cognitive and behaviour therapy , or self-help , these three treatments being of similar efficacy . Significantly more patients in the placebo group took additional psychotropic drugs in the 10 week period , and those allocated to dothiepin and cognitive and behaviour therapy took the least Background : Recent factor-analytic studies in obsessive-compulsive disorder ( OCD ) identified consistent symptom dimensions . Support for the validity of these dimensions comes from studies of psychiatric comorbidity , functional brain imaging , genetic transmission , and treatment response to medications . This study examined whether previously identified OCD symptom dimensions are associated with treatment compliance and response to behaviour therapy ( BT ) for OCD . Methods : One hundred and fifty-three OCD out patients who participated in a multi-centre r and omised controlled trial of computer- versus clinician-guided BT for OCD were included in the study . Logistic and multiple regression models tested for significant predictors of compliance with and response to BT and relaxation . Results : The patients studied were phenomenologically comparable ( including the presence of ‘ pure ’ obsessions and mental rituals ) to those in previous serotonin reuptake inhibitor ( SRI ) trials and those in clinical epidemiology studies . High scorers on the ‘ hoarding ’ dimension were more likely to drop out prematurely from the study and tended to improve less . For those completing treatment , the strongest predictor of outcome was pre-treatment severity . Initial depression scores were unrelated to outcome . After controlling for symptom severity , higher scores on the ‘ sexual/religious obsessions ’ factor predicted poorer outcome with BT , especially when computer-guided . Conclusions : BT is especially indicated for OCD patients with aggressive/checking , contamination/cleaning and symmetry/ordering symptoms . Previous accounts of unsuccessful BT in patients with hoarding symptoms may be due in part to their propensity to drop out earlier from treatment . Patients with sexual/religious obsessions , but not those with mental rituals , might respond less well to traditional BT techniques . Existing treatments need to be refined and /or new treatments developed to improve these patients ’ adherence and response to treatment Background Recent projections suggest that by the year 2030 depression will be the primary cause of disease burden among developed countries . Delivery of accessible consumer-focused evidence d-based services may be an important element in reducing this burden . Many consumers report a preference for self-help modes of delivery . The Internet offers a promising modality for delivering such services and there is now evidence that automated professionally developed self-help psychological interventions can be effective . By contrast , despite their popularity , there is little evidence as to the effectiveness of Internet support groups which provide peer-to-peer mutual support . Methods / Design Members of the community with elevated psychological distress were r and omised to receive one of the following : ( 1 ) Internet Support Group ( ISG ) intervention , ( 2 ) a multi-module automated psychoeducational and skills Internet Training Program ( ITP ) , ( 3 ) a combination of the ISG and ITP , or ( 4 ) an Internet Attention Control website ( IAC ) comprising health and wellbeing information and question and answer modules . Each intervention was 12 weeks long . Assessment s were conducted at baseline , post-intervention , 6 and 12 months to examine depressive symptoms , social support , self-esteem , quality of life , depression literacy , stigma and help-seeking for depression . Participants were recruited through a screening postal survey sent to 70,000 Australians aged 18 to 65 years r and omly selected from four rural and four metropolitan regions in Australia . Discussion To our knowledge this study is the first r and omised controlled trial of the effectiveness of a depression ISG.Trial registration Current Controlled Trials IS RCT N65657330 Objective : The purpose of the present study was to examine the effectiveness of an Internet-based clinician-assisted computerized cognitive behavioural therapy programme for social phobia . Method : A total of 105 individuals with social phobia were r and omly assigned to a six-lesson cognitive behavioural treatment programme or to a waitlist control group . Treatment consisted of four components : six online lessons ; homework assignments ; participation in an online discussion forum ; and regular email contact with a therapist . An intention-to-treat model was used for data analyses . Results : A total of 78 % of treatment group participants completed all lessons , and post-treatment data were obtained from 93/105 participants . Significant post-treatment differences between treatment and waitlist participants were found on two measures of symptoms of social phobia . Mean within- and between-group effect sizes ( Cohen 's d ) for the primary social phobia outcome measures were 1.15 , and 0.95 , respectively . Conclusions : These results were comparable with those obtained in exemplary face-to-face treatment programmes . They provide further positive data about the utility of Internet-based guided self-help programmes for people with common mental disorders Objective : In a r and omized controlled trial Titov et al. ( 2008 ) demonstrated significant benefit from an Internet- and email-based treatment programme for social phobia . The present study ( Shyness 2 ) seeks to replicate that finding and compares results with benchmark data . Method : Eighty-eight individuals with social phobia were r and omly assigned to a clinician-assisted computerized cognitive behavioural treatment programme or to a waitlist control group . Participants completed the same treatment programme used in Shyness 1 , consisting of six online lessons , cognitive behavioural homework assignments , email contact with a therapist , and participation in an online discussion forum . An intention-to-treat model was used for data analyses . Results : A total of 80 % of treatment group participants completed all lessons , and post-treatment data were obtained from 78/81 participants . Treatment group participants each had an average of 127 min of therapist contact over the 10 week programme , including an average of 22 email contacts plus therapist responses to forum postings . Pre- to post-treatment differences were seen between treatment and waitlist participants across two measures of symptoms of social phobia , and across a measure of disability . Mean within- and between-group effect sizes ( Cohen 's d ) across the two primary outcome measures were 1.18 , and 1.20 , respectively . Quantitative and qualitative data indicate that the procedure is very acceptable to participants . Conclusions : These results closely replicate those obtained in Shyness 1 , indicating that the treatment procedure is reliable . These results compare favourably with outcomes reported in benchmarking studies from high- quality face-to-face treatment programmes for social phobia . These results provide further positive data about the utility of Internet-based guided self-help programmes for people with social phobia It has been proposed that a persistent and pervasive tendency to avoid risks is involved in the development and maintenance of clinical ly significant anxiety . Few studies , however , have examined the clinical implication s of risk-aversion , and particularly the association between risk-aversion and treatment outcome . The current study investigated how risk-aversion in specific domains ( Social and Recreational ) related to treatment outcome in a clinical sample of patients with generalized anxiety disorder ( GAD ) undergoing internet-delivered cognitive-behavioral therapy ( CBT ) . We hypothesized that : ( i ) risk-taking would increase as a result of treatment and ( ii ) risk-taking would mediate changes in symptom severity and impairment as a result of treatment . Individuals recruited online ( N=44 ) meeting diagnostic criteria for GAD were r and omized to the treatment ( n=24 ) or control group ( n=20 ) . Participants completed measures of symptom severity , impairment and risk-taking before and after treatment . Results partially confirmed our hypotheses , demonstrating that participants in the treatment group significantly increased social and recreational risk-taking scores relative to the control group and risk-taking mediated treatment outcome for depression , but not for anxiety symptoms . The results of this study suggest that social and recreational risk-avoidance decreases following CBT treatment , and this change may mediate treatment outcome for depression . Clinical implication s of these findings are discussed BACKGROUND This study investigated the efficacy of an Internet-based self-help program with minimal therapist contact via e-mail for Swedish university students with social phobia and public speaking fears . The main objective was to test if the Internet-based self-help program would be more effective if five live group exposure sessions were added . METHODS Thirty-eight students meeting the diagnostic and statistical manual of mental disorders , 4th edition criteria for social phobia were r and omized into two different treatment groups : Internet delivered cognitive behavior therapy combined with five group exposure sessions ( ICBT+ exp ) or the Internet program alone ( ICBT ) . RESULTS Results were analyzed on an intention-to-treat basis . Both treatment groups showed significant improvement from pre- to post-test , and from pre-test to 1-year follow-up , on all measured dimensions ( social anxiety , general anxiety , depression levels , and quality of life ) . For both the groups , the average within-group effect sizes for the primary social anxiety scales , expressed as Cohen 's d , were comparable to those seen in traditionally administered cognitive behavioral therapy both at post-test and at 1- year follow-up . CONCLUSIONS The results suggest that the Internet-based self-help program on its own is efficient in the treatment of university students with social phobia . Adding group exposure sessions did not improve the outcome significantly |
13,856 | 23,728,680 | There is currently insufficient evidence that exercises or prescription of single lens glasses to multifocal users prevent falls or decrease the number of people falling after being discharged from rehabilitation following their stroke . | BACKGROUND Falls are one of the most common medical complications after stroke with a reported incidence of 7 % in the first week after stroke onset .
Studies investigating falls in the later phase after stroke report an incidence of up to 73 % in the first year post-stroke .
OBJECTIVES To evaluate the effectiveness of interventions aim ed at preventing falls in people after stroke . | BACKGROUND AND PURPOSE This prospect i ve , multicenter study was performed to determine the frequency of symptomatic complications up to 30 months after stroke using prespecified definitions of complications . METHODS We recruited 311 consecutive stroke patients admitted to hospital . Research nurses review ed their progress on a weekly basis until hospital discharge and again at 6 , 18 , and 30 months after stroke . RESULTS Complications during hospital admission were recorded in 265 ( 85 % ) of stroke patients . Specific complications were as follows : neurological-recurrent stroke ( 9 % of patients ) , epileptic seizure ( 3 % ) ; infections-urinary tract infection ( 24 % ) , chest infection ( 22 % ) , others ( 19 % ) ; mobility related-falls ( 25 % ) , falls with serious injury ( 5 % ) , pressure sores ( 21 % ) ; thromboembolism-deep venous thrombosis ( 2 % ) , pulmonary embolism ( 1 % ) ; pain-shoulder pain ( 9 % ) , other pain ( 34 % ) ; and psychological-depression ( 16 % ) , anxiety ( 14 % ) , emotionalism ( 12 % ) , and confusion ( 56 % ) . During follow-up , infections , falls , " blackouts , " pain , and symptoms of depression and anxiety remained common . Complications were observed across all 3 hospital sites , and their frequency was related to patient dependency and duration after stroke . CONCLUSIONS Our prospect i ve cohort study has confirmed that poststroke complications , particularly infections and falls , are common . However , we have also identified complications relating to pain and cognitive or affective symptoms that are potentially preventable and may previously have been underestimated Background and Purpose — Drop foot after stroke may be addressed using an ankle foot orthosis ( AFO ) or a foot drop stimulator ( FDS ) . The Functional Ambulation : St and ard Treatment versus Electric Stimulation Therapy ( FASTEST ) trial was a multicenter , r and omized , single-blinded trial comparing FDS and AFO for drop foot among people ≥3 months after stroke with gait speed ⩽0.8 m/s . Methods — Participants ( n=197 ; 79 females and 118 males ; 61.14±11.61 years of age ; time after stroke 4.55±4.72 years ) were r and omized to 30 weeks of either FDS or a st and ard AFO . Eight dose-matched physical therapy sessions were provided to both groups during the first 6 weeks of the trial . Results — There was significant improvement within both groups from baseline to 30 weeks in comfortable gait speed ( 95 % confidence interval for mean change , 0.11–0.17 m/s for FDS and 0.12–0.18 m/s for AFO ) and fast gait speed . However , no significant differences in gait speed were found in the between-group comparisons . Secondary outcomes ( st and ard measures of body structure and function , activity , and participation ) improved significantly in both groups , whereas user satisfaction was significantly higher in the FDS group than in the control group . Conclusions — Using either an FDS or an AFO for 30 weeks yielded clinical ly and statistically significant improvements in gait speed and other functional outcomes . User satisfaction was higher in the FDS group . Although both groups did receive intervention , this large clinical trial provides evidence that FDS or AFO with initial physical therapy sessions can provide a significant and clinical ly meaningful benefit even years after stroke . Clinical Trial Registration Information— URL : http://www . clinical trials.gov . Unique Identifier : NCT01138995 Background Falls are common in stroke survivors returning home after rehabilitation , however there is currently a lack of evidence about preventing falls in this population . This paper describes the study protocol for the FLASSH ( FaLls prevention After Stroke Survivors return Home ) project . Methods and design This r and omised controlled trial aims to evaluate the effectiveness of a multi-factorial falls prevention program for stroke survivors who are at high risk of falling when they return home after rehabilitation . Intervention will consist of a home exercise program as well as individualised falls prevention and injury minimisation strategies based on identified risk factors for falls . Additionally , two sub- studies will be implemented in order to explore other key areas related to falls in this population . The first of these is a longitudinal study evaluating the relationship between fear of falling , falls and function over twelve months , and the second evaluates residual impairment in gait stability and obstacle crossing twelve months after discharge from rehabilitation . Discussion The results of the FLASSH project will inform falls prevention practice for stroke survivors . If the falls prevention program is shown to be effective , low cost strategies to prevent falls can be implemented for those at risk around the time of discharge from rehabilitation , thus improving safety and quality of life for stroke survivors . The two sub- studies will contribute to the overall underst and ing and management of falls risk in stroke survivors . Trial registration This trial is registered with the Australian and New Zeal and Clinical Trials Registry ( ACTRN012607000398404 ) Objectives To investigate if repeated verbal instructions about physical activity to patients with ischaemic stroke could increase long term physical activity . Design Multicentre , multinational , r and omised clinical trial with masked outcome assessment . Setting Stroke units in Denmark , China , Pol and , and Estonia . Participants 314 patients with ischaemic stroke aged ≥40 years who were able to walk—157 ( mean age 69.7 years ) r and omised to the intervention , 157 ( mean age 69.4 years ) in the control group . Interventions Patients r and omised to the intervention were instructed in a detailed training programme before discharge and at five follow-up visits during 24 months . Control patients had follow-up visits with the same frequency but without instructions in physical activity . Main outcome measures Physical activity assessed with the Physical Activity Scale for the Elderly ( PASE ) at each visit . Secondary outcomes were clinical events . Results The estimated mean PASE scores were 69.1 in the intervention group and 64.0 in the control group ( difference 5.0 ( 95 % confidence interval −5.8 to 15.9 ) , P=0.36 . The intervention had no significant effect on mortality , recurrent stroke , myocardial infa rct ion , or falls and fractures . Conclusion Repeated encouragement and verbal instruction in being physically active did not lead to a significant increase in physical activity measured by the PASE score . More intensive strategies seem to be needed to promote physical activity after ischaemic stroke . Trial registration Clinical Trials Background and Purpose — The optimal organization of rehabilitation services after discharge from a stroke unit has not been determined . This study sought to evaluate the effect of early supported discharge and continued rehabilitation at home ( ESD ) , in terms of patient outcome 5 years after stroke and changes in selected data over time . Methods — Eighty-three patients from Southwest Stockholm , mildly or moderately impaired 5 to 7 days after acute stroke , were enrolled in a r and omized controlled trial . The core components of the ESD service were initial treatment in a stroke unit and the involvement of an outreach team to deliver and coordinate home-based rehabilitation in partnership with the patient . At the 5-year follow-up , measures used to assess patient outcome included survival , motor capacity , dysphasia , activities of daily living ( ADL ) , social activities , subjective dysfunction , and self-reported falls . Results — Fifty-four patients ( 30 in the intervention group and 24 in the control group ) were evaluated 5 years after stroke , at which time a significantly larger proportion of patients in the intervention group were independent in extended ADL and active in household activities . Conclusions — This ESD service has a beneficial effect on extended ADL 5 years after stroke for mildly to moderately impaired patients BACKGROUND Locomotor training , including the use of body-weight support in treadmill stepping , is a physical therapy intervention used to improve recovery of the ability to walk after stroke . The effectiveness and appropriate timing of this intervention have not been established . METHODS We stratified 408 participants who had had a stroke 2 months earlier according to the extent of walking impairment -- moderate ( able to walk 0.4 to < 0.8 m per second ) or severe ( able to walk < 0.4 m per second)-- and r and omly assigned them to one of three training groups . One group received training on a treadmill with the use of body-weight support 2 months after the stroke had occurred ( early locomotor training ) , the second group received this training 6 months after the stroke had occurred ( late locomotor training ) , and the third group participated in an exercise program at home managed by a physical therapist 2 months after the stroke ( home-exercise program ) . Each intervention included 36 sessions of 90 minutes each for 12 to 16 weeks . The primary outcome was the proportion of participants in each group who had an improvement in functional walking ability 1 year after the stroke . RESULTS At 1 year , 52.0 % of all participants had increased functional walking ability . No significant differences in improvement were found between early locomotor training and home exercise ( adjusted odds ratio for the primary outcome , 0.83 ; 95 % confidence interval [ CI ] , 0.50 to 1.39 ) or between late locomotor training and home exercise ( adjusted odds ratio , 1.19 ; 95 % CI , 0.72 to 1.99 ) . All groups had similar improvements in walking speed , motor recovery , balance , functional status , and quality of life . Neither the delay in initiating the late locomotor training nor the severity of the initial impairment affected the outcome at 1 year . Ten related serious adverse events were reported ( occurring in 2.2 % of participants undergoing early locomotor training , 3.5 % of those undergoing late locomotor training , and 1.6 % of those engaging in home exercise ) . As compared with the home-exercise group , each of the groups receiving locomotor training had a higher frequency of dizziness or faintness during treatment ( P=0.008 ) . Among patients with severe walking impairment , multiple falls were more common in the group receiving early locomotor training than in the other two groups ( P=0.02 ) . CONCLUSIONS Locomotor training , including the use of body-weight support in stepping on a treadmill , was not shown to be superior to progressive exercise at home managed by a physical therapist . ( Funded by the National Institute of Neurological Disorders and Stroke and the National Center for Medical Rehabilitation Research ; LEAPS Clinical Trials.gov number , NCT00243919 . ) QUESTIONS Is treadmill walking with body weight support during inpatient rehabilitation detrimental to walking quality compared with assisted overground walking ? Does it result in better walking capacity , perception of walking or community participation ? DESIGN Analysis of secondary outcomes of a r and omised trial with concealed allocation , assessor blinding and intention-to-treat analysis . PARTICIPANTS 126 patients unable to walk within 4 weeks of a stroke who were undergoing inpatient rehabilitation . INTERVENTION The experimental group undertook up to 30 minutes of treadmill walking with body weight support via an overhead harness per day while the control group undertook up to 30 minutes of overground walking . OUTCOME MEASURES The secondary outcomes were walking quality and capacity , walking perception , community participation and falls . RESULTS Six months after entering the study , there was no difference between the groups of independent walkers in terms of speed ( MD 0.10 m/s , 95 % CI -0.06 to 0.26 ) or stride ( MD 6 cm , 95 % CI -7 to 19 ) . The independent walkers in the experimental group walked 57 m further ( 95 % CI 1 to 113 ) in the 6 min walk than those in the control group . The experimental group ( walkers and non-walkers ) rated their walking 1 point out of 10 ( 95 % CI 0.1 to 1.9 ) higher than the control group . There was no difference between the groups in community participation or number of falls . CONCLUSION Treadmill training with body weight support results in better walking capacity and perception of walking compared to overground walking without deleterious effects on walking quality BACKGROUND AND PURPOSE This study describes the methodology , patient outcome , and use of hospital and rehabilitation services at 3 months of a population -based r and omized controlled trial . The purpose was to evaluate rehabilitation at home after early supported discharge from the Department of Neurology , Huddinge Hospital , for moderately disabled stroke patients in southwest Stockholm . METHODS The patients were eligible if they were continent , independent in feeding , had mental function within normal limits , and had impaired motor function and /or aphasia 1 week after stroke . Patients were r and omized either to early supported discharge with continuity of rehabilitation at home for 3 to 4 months or to routine rehabilitation service in a hospital , day care , and /or outpatient care . The home rehabilitation team consisted of two physical therapists , two occupational therapists , and one speech therapist ; one of the therapists was assigned as case manager for the patient . The rehabilitation program at home emphasized a task- and context -oriented approach . The activities were chosen on the basis of the patient 's personal interests . Spouses were offered education and individual counseling . A total of 81 patients were followed up for a minimum of 3 months . Patient outcome was assessed by the Frenchay Social Activity Index , Extended Katz Index , Barthel Index , Lindmark Motor Capacity Assessment , Nine-Hole Peg Test , walking speed over 10 m , reported falls , and subjective dysfunction according to the Sickness Impact Profile . Patient use of hospital and home rehabilitation service and patient satisfaction with care were studied . RESULTS Overall there were no statistical significant differences in outcome . Multivariate logistic regression analysis suggested a systematic positive effect for the home rehabilitation group in social activity , activities of daily living , motor capacity , manual dexterity , and walking . A considerable difference in re source use during such a 3-month period was seen . A 52 % reduction in hospitalization was observed : from 29 days in the routine rehabilitation group to 14 days in the home rehabilitation group . Patient satisfaction was in favor of the latter group . CONCLUSIONS Early supported discharge with continuity of home rehabilitation services for the majority of moderately disabled stroke patients during the first 3-month period after acute stroke is not less beneficial than routine rehabilitation and can be a rehabilitation service of choice if follow-up at 6 and 12 months confirms the suggested effectiveness and considerable reduction in use of health care BACKGROUND Community physiotherapy is often prescribed for stroke patients with long-term mobility problems . We aim ed to assess the effectiveness of this treatment in patients who had mobility problems 1 year after stroke . METHODS We screened 359 patients older than 50 years for a single-masked , r and omised controlled trial to assess the effects of community physiotherapy . Assessment s were made at baseline , 3 , 6 , and 9 months in 170 eligible patients assigned treatment or no intervention . The primary outcome measure was mobility measured by the Rivermead mobility index . Secondary outcome measures were gait speed , number of falls , daily activity ( Barthel index scores ) , social activity ( Frenchay activities index ) , hospital anxiety and depression scale , and emotional stress of carers ( general health question naire 28 ) . Analyses were by intention to treat . FINDINGS Follow-up was available for 146 patients ( 86 % ) . Changes in scores on the Rivermead mobility index ( score range 0 - 15 ) differed significantly between treatment and control groups at 3 months ( p=0.018 ) , but only by a median of 1 point ( 95 % CI 0 - 1 ) , with an interpolated value of 0.55 ( 0.08 - 1.04 ) . Gait speed was 2.6 m/min ( 0.30 - 4.95 ) higher in the treatment group at 3 months . Neither treatment effect persisted at 6-months ' and 9-months ' follow-up . Treatment had no effect on patients ' daily activity , social activity , anxiety , depression , and number of falls , or on emotional stress of carers . INTERPRETATION Community physiotherapy treatment for patients with mobility problems 1 year after stroke leads to significant , but clinical ly small , improvements in mobility and gait speed that are not sustained after treatment ends BACKGROUND There is a high incidence of hip fractures in patients after hemiplegic stroke . Bone mineral density is decreased on the hemiplegic side in patients after stroke , correlating with the immobilization-induced bone resorption , the degree of paralysis , and hypovitaminosis D. The purpose of this study is to evaluate the effectiveness of risedronate sodium , an inhibitor of bone resorption , on osteoporosis and the risk of hip fractures in men 65 years or older after stroke . METHODS We conducted an 18-month r and omized double-blind trial . Of 280 male patients 65 years or older who were poststroke , 140 received a daily dose of 2.5 mg risedronate sodium and the other 140 received placebo . Incidence of hip fractures in the 2 groups was compared . RESULTS Ten patients sustained hip fractures in the placebo group , and 2 hip fractures occurred in the risedronate group . The relative risk of a hip fracture was 0.19 ( 95 % confidence interval , 0.04 - 0.89 ) . The number of patients needing the treatment was 16 ( 95 % confidence interval , 9 - 32 ) . Bone mineral density increased by 2.5 % in the risedronate group and decreased by 3.5 % in the placebo group ( P<.001 ) . Urinary deoxypyridinoline , a bone resorption marker , decreased by 58.7 % in the risedronate group and by 37.2 % in the placebo group . CONCLUSION Treatment with risedronate increases bone mineral density and reduces hip fractures in elderly men who are poststroke BACKGROUND The authors ' previous investigations have disclosed low serum 25-hydroxyvitamin D ( 25-OHD ) concentrations in 45 patients during long-term hospitalization following stroke ( mean 5.9 ng/mL ) . This 25-OHD deficiency result ed from sunlight deprivation . OBJECTIVE To evaluate the efficacy of sunlight exposure in increasing serum 25-OHD , in reducing the severity of osteoporosis in bone mineral density ( BMD ) , and in decreasing the risk of hip fractures in chronically hospitalized , disabled stroke patients . METHODS In a 12-month r and omized and prospect i ve study of stroke patients , 129 received regular sunlight exposure for 12 months , and the remaining 129 ( sunlight-deprived ) did not . RESULTS At baseline , patients of both groups showed vitamin D deficiency . BMD increased by 3.1 % in the sunlight-exposed group and decreased by 3.3 % in the sunlight-deprived group ( p = 0.0001 ) . 25-OHD level increased by fourfold in the sunlight-exposed group . Six patients sustained hip fractures on the hemiplegic side in the sunlight-deprived group , and one hip fracture occurred among the sunlight-exposed group ( p = 0421 ; odds ratio = 6.1 ) . CONCLUSION Sunlight exposure can increase the BMD of vitamin D-deficient bone by increasing 25-OHD concentration Background and Purpose — The main objective of this r and omized trial was to determine whether treadmill walking with body weight support was effective at establishing independent walking more often and earlier than current physiotherapy intervention for nonambulatory stroke patients . Methods — A r and omized trial with concealed allocation , blinded assessment , and intention-to-treat analysis was conducted . One hundred twenty-six stroke patients who were unable to walk were recruited and r and omly allocated to an experimental or a control group within 4 weeks of stroke . The experimental group undertook up to 30 minutes per day of treadmill walking with body weight support via an overhead harness whereas the control group undertook up to 30 minutes of overground walking . The primary outcome was the proportion of participants achieving independent walking within 6 months . Results — Kaplan – Meier estimates of the proportion of experimental participants who achieved independent walking were 37 % compared with 26 % of the control group at 1 month , 66 % compared with 55 % at 2 months , and 71 % compared with 60 % at 6 months ( P=0.13 ) . The experimental group walked 2 weeks earlier , with a median time to independent walking of 5 weeks compared to 7 weeks for the control group . In addition , 14 % ( 95 % CI , −1–28 ) more of the experimental group were discharged home . Conclusions — Treadmill walking with body weight support is feasible , safe , and tends to result in more people walking independently and earlier after stroke . Trial Registration — NN Clinical Trial.gov ( NCT00167531 ) Introduction The current study aims to investigate the effects of primary caregiver participation in vestibular rehabilitation ( VR ) on improving the measures of neglect , activities of daily living ( ADL ) , balance , and falls of unilateral neglect ( UN ) patients . Methods This study is a single-blind r and omized controlled trial . Both experimental ( n = 24 ) and control groups ( n = 24 ) received conventional rehabilitation . The experimental group undertook VR for a month . During the first and second weeks , a registered nurse trained the experimental group in VR . The primary caregivers in the experimental group supervised and guided their patients in VR during the third and fourth weeks . The outcome measures were neglect , ADL , balance , and falls . Results The two groups of UN patients showed a significant improvement in neglect , ADL , and balance over time . Based on the generalized estimating equations model , an interaction was observed between groups and times . Significant interactions were observed between the VR group at days 14 and 28 in the areas of neglect , ADL , and balance . No significant difference was observed between the two groups in the number of falls . Conclusion Neglect , ADL , and balance among UN patients with right hemispheric stroke can be improved through the participation of primary caregivers in VR . Trained informal caregivers were recommended to provide VR guidance and supervision to patients who suffer from UN Background . Exercise interventions can enhance mobility after stroke as well as prevent falls in elderly persons . Objective . Investigate whether an exercise intervention can enhance mobility , prevent falls , and increase physical activity among community-dwelling people after stroke . Method . A r and omized trial with blinding of physical outcome assessment was conducted through local stroke clubs . Both groups , on average 5.9 years poststroke , received exercise classes , advice , and a home program for 12 months . The experimental group ( EG ) program ( n = 76 ) aim ed to improve walking , prevent falls and increase physical activity . The control group ( CG ) program ( n = 75 ) aim ed to improve upper-limb and cognitive functions . The primary outcomes were walking capacity , walking speed measured before and after the intervention , and fall rates monitored monthly . Results . At 12 months , the EG walked 34 m further in 6 minutes ( 95 % confidence interval [ CI ] = 19 - 50 ; P < .001 ) and 0.07 m/s faster over 10 m ( 95 % CI = 0.01 - 0.14 ; P = .03 ) than the CG . The EG had 129 falls , and the CG had 133 . There were no differences in proportion of fallers ( relative risk = 1.22 ; 95 % CI = 0.91 - 1.62 ; P = .19 ) or the rate of falls between groups ( incidence rate ratio = 0.96 ; 95 % CI = 0.59 - 1.51 ; P = .88 ) . Conclusion . The experimental intervention delivered through stroke clubs enhanced aspects of mobility but had no effect on falls Background Residual walking deficits are common in community-dwelling people after stroke . Aims The aim of this study was to determine if a four-month treadmill and overground walking program is more effective than a two-month program , compared with control , at improving walking in community-dwelling people with stroke who walk slowly . Method A three-arm r and omized trial with concealed allocation , assessor blinding , and intention-to-treat analysis involving 102 people with stroke living in the community who walked slowly was undertaken . Experimental group 1 undertook 30 min of treadmill and overground walking thrice per week for four-months , experimental group 2 undertook training for two-months , while the control group had no intervention . The primary outcome was walking measured as the distance covered during the six-min walk test . Other outcomes were walking speed , step length and cadence , health status , community participation , self-efficacy and falls . Results By two-months , the experimental groups , who were both undergoing training , had improved their six-min walk distance compared with the control group . The four-month training group continued training beyond two-months and improved further so that by four months they walked 38 m ( 95 % confidence interval 15–60 ) more than the control group and 29 m ( 95 % confidence interval 4–53 ) more than the two-month training group . However , by 12 months , well after the cessation of training , both experimental groups had returned to near baseline levels , and there was no difference between the groups . Conclusion Four months of treadmill training results in better walking . However , these effects disappear once training ceases . Therefore , training should be ongoing Background and Purpose — Very early rehabilitation , with an emphasis on mobilization , may contribute to improved outcomes after stroke . We hypothesized that a very early rehabilitation protocol would be safe and feasible . Methods — We performed a r and omized , controlled trial with blinded outcome assessment . Patients at < 24 hours after stroke were recruited from 2 Melbourne metropolitan stroke units . Patients were r and omly assigned to receive st and ard care ( SC ) or SC plus very early mobilization ( VEM ) until discharge or 14 days ( whichever was sooner ) . The primary safety outcome was the number of deaths at 3 months . The primary feasibility outcome was a higher “ dose ” of mobilization achieved in VEM . Secondary safety outcomes included adverse events ( including falls and early neurologic deterioration ) , compliance with physiologic monitoring criteria , and patient fatigue after interventions . Secondary feasibility outcomes included “ contamination ” of st and ard care . Results — Overall , 18 % of patients screened were suitable for recruitment . Seventy-one patients were recruited and r and omized , with 2 dropouts by 12 months . The majority experienced ischemic strokes ( 87 % ) . The group mean±SD age was 74.7±12.5 years , and 58 % ( n=41 ) had a National Institutes of Health Stroke Scale score > 7 . There was no significant difference in the number of deaths between groups ( SC , 3 of 33 ; VEM , 8 of 38 ; P=0.20 ) . Almost all deaths occurred in patients with severe stroke . Secondary safety outcomes were similar between groups . The intervention protocol was successfully delivered , achieving VEM dose targets ( double SC , P=0.003 ) and faster time to first mobilization ( P<0.001 ) . Conclusions — VEM of patients within 24 hours of acute stroke appears safe and feasible . Intervention efficacy and cost-effectiveness are currently being tested in a large r and omized , controlled trial The CONSORT ( Consoli date d St and ards of Reporting Trials ) statement is used worldwide to improve the reporting of r and omized , controlled trials . 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 . Objective . Gait performance is an indicator of mobility impairment after stroke . This study evaluated changes in balance , lower extremity motor function , and spatiotemporal gait parameters after receiving body weight supported treadmill training ( BWSTT ) and conventional overground walking training ( CT ) in patients with subacute stroke using 3D motion analysis . Setting . Inpatient department of rehabilitation medicine at a university-affiliated hospital . Participants . 24 subjects with unilateral hemiplegia in the subacute stage were r and omized to the BWSTT ( n = 12 ) and CT ( n = 12 ) groups . Parameters were compared between the two groups . Data from twelve age matched healthy subjects were recorded as reference . Interventions . Patients received gait training with BWSTT or CT for an average of 30 minutes/day , 5 days/week , for 3 weeks . Main Outcome Measures . Balance was measured by the Brunel balance assessment . Lower extremity motor function was evaluated by the Fugl-Meyer assessment scale . Kinematic data were collected and analyzed using a gait capture system before and after the interventions . Results . Both groups improved on balance and lower extremity motor function measures ( P < 0.05 ) , with no significant difference between the two groups after intervention . However , kinematic data were significantly improved ( P < 0.05 ) after BWSTT but not after CT . Maximum hip extension and flexion angles were significantly improved ( P < 0.05 ) for the BWSTT group during the stance and swing phases compared to baseline . Conclusion . In subacute patients with stroke , BWSTT can lead to improved gait quality when compared with conventional gait training . Both methods can improve balance and motor function Background Interventions for preventing falls in older people often involve several components , multidisciplinary teams , and implementation in a variety of setting s. We have developed a classification system ( taxonomy ) to describe interventions used to prevent falls in older people , with the aim of improving the design and reporting of clinical trials of fall-prevention interventions , and synthesis of evidence from these trials . Methods Thirty three international experts in falls prevention and health services research participated in a series of meetings to develop consensus . Robust techniques were used including literature review s , expert presentations , and structured consensus workshops moderated by experienced facilitators . The taxonomy was refined using an international test panel of five health care practitioners . We assessed the chance corrected agreement of the final version by comparing taxonomy completion for 10 r and omly selected published papers describing a variety of fall-prevention interventions . Results The taxonomy consists of four domains , summarized as the " Approach " , " Base " , " Components " and " Descriptors " of an intervention . Sub-domains include ; where participants are identified ; the theoretical approach of the intervention ; clinical targeting criteria ; details on assessment s ; descriptions of the nature and intensity of interventions . Chance corrected agreement of the final version of the taxonomy was good to excellent for all items . Further independent evaluation of the taxonomy is required . Conclusions The taxonomy is a useful instrument for characterizing a broad range of interventions used in falls prevention . Investigators are encouraged to use the taxonomy to report their interventions This purpose of this study was to determine whether an identification bracelet is effective in preventing falls among high-risk patients who are undergoing in-patient physical rehabilitation . A stratified , r and omized , balanced controlled clinical trial was conducted ; participants were blinded as to the outcome and the study hypothesis . All patients having one or more risk factors that predisposed them to falls were r and omized to receive either a blue identification bracelet or no bracelet . The identification bracelet was intended to increase patients ' vigilance about falling . Two risk strata were specified . The high risk stratum consisted of patients with stroke or ataxia , urinary incontinence , or a history of falls . The low risk stratum comprised patients older than 80 years and those on one or more medications that had been identified as contributing to an individual 's risk of falling . This report presents the effect of the identification bracelet only among persons in the high-risk stratum . Over 1 year , 65 high-risk subjects were r and omized to receive the blue identification bracelet and 69 high-risk subjects were controls . In the intervention group , 27 persons ( 41 % ) fell at least once , whereas in the control group 21 persons ( 30 % ) fell at least once yielding a hazard ratio of 1.3 ( 95 % confidence interval : 0.8 to 2.4 ) . These results suggest that the identification system was of no benefit in preventing falls among high-risk persons Background and Purpose — The aims of the study were to examine the frequency and timing of predefined medical complications in unselected acute stroke patients treated in an acute comprehensive stroke unit and an early supported discharge service . Methods — Four hundred eighty-nine acute stroke patients were included and followed up with assessment s of 16 prespecified complications during the first week . Two hundred forty-four of the patients were r and omly allocated to a 3-month follow-up . Results — During the first week , 312 of 489 patients ( 63.8 % ) experienced 1 or more complications . The most common complications were pain in 117 patients ( 23.9 % ) , temperature ≥38 ° C in 116 ( 23.7 % ) , progressing stroke in 90 ( 18.4 % ) , urinary tract infection in 78 ( 16.0 % ) , troponin T elevation without criteria of myocardial infa rct ion in 57 ( 11.7 % ) , chest infections in 55 ( 11.2 % ) , nonserious falls in 36 ( 7.4 % ) , and myocardial infa rct ion in 22 ( 4.5 % ) , whereas stroke recurrence , seizure , deep venous thrombosis , pulmonary embolism , shoulder pain , serious falls , other infections , and pressure sores were each present in ≤2.5 % of patients . During the 3-month follow-up , 201 of 244 patients ( 82.4 % ) experienced at least 1 complication , the most common of which was pain , which occurred in 134 patients ( 53.3 % ) , followed by urinary tract infection in 68 ( 27.9 % ) and nonserious falls in 61 ( 25.0 % ) . The severity of stroke on admission was the most important risk factor for developing complications . Conclusions — This is the first study of complications in unselected acute stroke patients treated in a comprehensive stroke unit and early supported discharge service and shows that pain , progressing stroke , infections , myocardial infa rct ion , and falls are common complications , whereas others occur infrequently . Most complications occur during the first 4 days , and stroke severity is the most important risk factor Background Stroke is the most common disabling neurological condition in adults . Falls and poor mobility are major contributors to stroke-related disability . Falls are more frequent and more likely to result in injury among stroke survivors than among the general older population . Currently there is good evidence that exercise can enhance mobility after stroke , yet ongoing exercise programs for general community-based stroke survivors are not routinely available . This r and omised controlled trial will investigate whether exercise can reduce fall rates and increase mobility and physical activity levels in stroke survivors . Methods and design Three hundred and fifty community dwelling stroke survivors will be recruited . Participants will have no medical contradictions to exercise and be cognitively and physically able to complete the assessment s and exercise program . After the completion of the pre-test assessment , participants will be r and omly allocated to one of two intervention groups . Both intervention groups will participate in weekly group-based exercises and a home program for twelve months . In the lower limb intervention group , individualised programs of weight-bearing balance and strengthening exercises will be prescribed . The upper limb/cognition group will receive exercises aim ed at management and improvement of function of the affected upper limb and cognition carried out in the seated position . The primary outcome measures will be falls ( measured with 12 month calendars ) and mobility . Secondary outcome measures will be risk of falling , physical activity levels , community participation , quality of life , health service utilisation , upper limb function and cognition . Discussion This study aims to establish and evaluate community-based sustainable exercise programs for stroke survivors . We will determine the effects of the exercise programs in preventing falls and enhancing mobility among people following stroke . This program , if found to be effective , has the potential to be implemented within existing community services . Trial registration The protocol for this study is registered with the Australian New Zeal and Clinical Trials Registry ( ACTRN12606000479505 ) Abstract The aim of the study was to evaluate the impact of a high-intensive exercise program containing high-intensive functional exercises implemented to real-life situations together with group discussion s on falls and security aspects in stroke subjects with risk of falls . This was a pre-specified secondary outcome for this study . For evaluation , Short Form-36 ( SF-36 ) health-related quality of life ( HRQoL ) and the Geriatric Depression Scale-15 ( GDS-15 ) were used . This was a single-center , single-blinded , r and omized , controlled trial . Consecutive ≥55 years old stroke patients with risk of falls at 3–6 months after first or recurrent stroke were r and omized to the intervention group ( IG , n=15 ) or to the control group ( CG , n=19 ) who received group discussion with focus on hidden dysfunctions but no physical fitness training . The 5-week high-intensive exercise program was related to an improvement in the CG in the SF-36 Mental Component Scale and the Mental Health subscale at 3 months follow-up compared with baseline values while no improvement was seen in the IG at this time . For the SF-36 Physical Component Scale , there was an improvement in the whole study group at 3 and 6 months follow-up compared with baseline values without any significant changes between the IG and CG . The GDS-15 was unchanged throughout the follow-up period for both groups . Based on these data , it is concluded that high-intensive functional exercises implemented in real-life situations should also include education on hidden dysfunctions after stroke instead of solely focus on falls and safety aspects to have a favorable impact on Background and Purpose — The benefits of chronic disease self-management programs for stroke survivors are uncertain because individuals with severe impairments have been excluded from previous research . We undertook a phase II r and omized controlled trial to determine whether a self-management program design ed for survivors ( SSMP ; 8 weeks ) was safe and feasible compared to st and ard care ( control ) or a generic self-management program ( generic ; 6 weeks ) . Methods — Stroke survivors were recruited from 7 South Australian hospitals via a letter or indirectly ( eg , newspapers ) . Eligible participants were r and omized at a 1:1:1 ratio of 50 per group . Primary outcomes were recruitment , participation , and participant safety . Secondary outcomes were positive and active engagement in life using the Health Education Impact Question naire and characteristics of quality of life and mood at 6 months from program completion . Results — Of 315 people screened , 149 were eligible and 143 were r and omized ( 48 SSMP , 47 generic , 48 control ) ; mean age was 69 years ( SD , 11 ) and 59 % were female . Demographic features were similar between groups and 41 % had severe cognitive impairment ; 57 % accessed the interventions , with 52 % SSMP and 38 % generic completing > 50 % of sessions ( P=0.18 ) . Thirty-two participants reported adverse events ( 7 control , 12 generic , 13 SSMP ; P=0.3 ; 34 % severe ) ; however , none was attributable to the interventions . Potential benefits for improved mood were found . Conclusions — SSMP was safe and feasible . Benefits of the stroke-specific program over the generic program included greater participation and completion rates . An efficacy trial is warranted given the forecast growth in the stroke population and improved survival trends Background Supine recumbence has been widely performed to prevent post-lumbar puncture headache ( PLPH ) . However , the optimal duration of supine recumbence is controversial . The aim of the study is to compare the occurrence of PLPH according to the duration of supine recumbence in patients with neurological disorders . Methods A non-equivalent control/experimental pre-/post-test study design was used . Seventy consecutive patients were prospect ively enrolled between July 2007 and July 2008 . Thirty-five patients underwent supine recumbence for four hours after lumbar puncture ( Group 1 ) and 35 patients underwent supine recumbence for one hour ( Group 2 ) . Results The overall frequency of PLPH was 31.4 % . The frequency of PLPH was not significantly different between the Group 1 ( 28.6 % ) and Group 2 ( 34.3 % ) ( P = 0.607 ) . In patients with PLPH , the median severity ( P = 0.203 ) and median onset time of PLPH ( P = 0.582 ) were not significantly different between the two groups . In a logistic regression analysis , the previous history of post-lumbar puncture headache was a significant risk factor for the occurrence of PLPH ( OR = 11.250 , 95 % CI : 1.10 - 114.369 , P = 0.041 ) . Conclusions Our study suggests that short duration ( one hour ) of supine recumbence may be as efficient as long duration ( four hours ) of supine recumbence to prevent PLPH A 6-month follow-up of a single-blind , r and omized , controlled trial in Southwest Stockholm was performed in order to evaluate the effect of early supported discharge and continued rehabilitation at home after stroke . Eighty-three stroke patients with moderate neurological impairments , continent , independent in feeding , and mental function within normal limits one week after onset were included in the study . The patients were allocated 1:1 to early supported discharge and continued rehabilitation at home by a specialized team , versus routine rehabilitation . Patient outcomes measured were motor capacity , dysphasia , activities of daily living , social activities , perceived dysfunction , mortality and reported falls . Data on length of stay in hospital ; initial and recurrent during 6 months were compared . The 6-month follow-up of 78 patients showed no statistically significant differences in patient outcome . The results of multivariate logistic regression analysis suggest a positive effect of home rehabilitation on activities of daily living . At 3 - 6 months the frequency of significant improvements was higher in the intervention group . Death or dependency in activities of daily living was 24 % in the intervention group compared with 44 % in the control group . The mean initial hospitalization was 29 days in routine rehabilitation group versus 14 days in the home rehabilitation group . We conclude that for moderately disabled stroke patients with mental function within normal limits , early supported discharge and continued rehabilitation at home had no less a beneficial effect on patient outcome than routine rehabilitation , reduced initial hospitalization significantly and had no adverse effects on mortality and number of falls OBJECTIVES To determine the effect of two different community-based group exercise programs on functional balance , mobility , postural reflexes , and falls in older adults with chronic stroke . DESIGN A r and omized , clinical trial . SETTING Community center . PARTICIPANTS Sixty-one community-dwelling older adults with chronic stroke . INTERVENTION Participants were r and omly assigned to an agility ( n=30 ) or stretching/weight-shifting ( n=31 ) exercise group . Both groups exercised three times a week for 10 weeks . MEASUREMENTS Participants were assessed before , immediately after , and 1 month after the intervention for Berg Balance , Timed Up and Go , step reaction time , Activities-specific Balance Confidence , and Nottingham Health Profile . Testing of st and ing postural reflexes and induced falls evoked by a translating platform was also performed . In addition , falls in the community were tracked for 1 year from the start of the interventions . RESULTS Although exercise led to improvements in all clinical outcome measures for both groups , the agility group demonstrated greater improvement in step reaction time and paretic rectus femoris postural reflex onset latency than the stretching/weight-shifting group . In addition , the agility group experienced fewer induced falls on the platform . CONCLUSION Group exercise programs that include agility or stretching/weight shifting exercises improve postural reflexes , functional balance , and mobility and may lead to a reduction of falls in older adults with stroke Objective To determine whether the provision of single lens distance glasses to older wearers of multifocal glasses reduces falls . Design Parallel r and omised controlled trial stratified by recruitment site and source of referral , with 13 months ’ follow-up and outcome assessors blinded to group allocation . Setting Community recruitment and treatment room assessment s in Sydney and Illawarra regions of NSW , Australia . Participants 606 regular wearers of multifocal glasses ( mean age 80 ( SD 7 ) years ) . Inclusion criteria included increased risk of falls ( fall in previous year or timed up and go test > 15 seconds ) and outdoor use of multifocal glasses at least three times a week . Interventions Provision of single lens distance glasses with recommendations for wearing them for walking and outdoor activities compared with usual care . Main outcome measures Number of falls and injuries result ing from falls during follow-up . Results Single lens glasses were provided to 275 ( 90 % ) of the 305 intervention group participants within two months ; 162 ( 54 % ) of the intervention group reported satisfactory use of distance glasses for walking and outdoor activities for at least 7/12 months after dispensing . In the 299 intervention and 298 control participants available to follow-up , the intervention result ed in an 8 % reduction in falls ( incidence rate ratio 0.92 , 95 % confidence interval 0.73 to 1.16 ) . Pre-planned sub-group analyses showed that the intervention was effective in significantly reducing all falls ( incidence rate ratio 0.60 , 0.42 to 0.87 ) , outside falls , and injurious falls in people who regularly took part in outside activities . A significant increase in outside falls occurred in people in the intervention group who took part in little outside activity . Conclusions With appropriate counselling , provision of single lens glasses for older wearers of multifocal glasses who take part in regular outdoor activities is an effective falls prevention strategy . The intervention may be harmful , however , in multifocal glasses wearers with low levels of outdoor activity . Trial registration Clinical trials NCT00350855 Background Recent research has shown that wearing multifocal glasses increases the risk of trips and falls in older people . The aim of this study is to determine whether the provision of single-lens distance glasses to older multifocal glasses wearers , with recommendations for wearing them for walking and outdoor activities , can prevent falls . We will also measure the effect of the intervention on health status , lifestyle activities and fear of falling , as well as the extent of adherence to the program . Methods / Design Approximately 580 older people who are regular wearers of multifocal glasses people will be recruited . Participants will be r and omly allocated to either an intervention group ( provision of single lens glasses , with counselling and advice about appropriate use ) or a control group ( usual care ) . The primary outcome measure will be falls ( measured with 13 monthly calendars ) . Secondary measures will be quality of life , falls efficacy , physical activity levels and adverse events . Discussion sThe study will determine the impact of providing single-lens glasses , with advice about appropriate use , on preventing falls in older regular wearers of multifocal glasses . This pragmatic intervention , if found to be effective , will guide practitioners with regard to recommending appropriate glasses for minimising the risk of falls in older people . Trial Registration The protocol for this study was registered with the Clinical Trials.gov Protocol Registration System on June 7th 2006 ( # 350855 ) Background It has been reported that only half of the non-ambulatory stroke patients admitted to inpatient rehabilitation in Australia learn to walk again [ 1 ] . Treadmill walking with partial weight support via an overhead harness is a relatively new intervention that is design ed to train walking . The main objective of this r and omised controlled trail is to determine whether treadmill walking with partial weight support via an overhead harness is effective at establishing independent walking ( i ) more often , ( ii ) earlier and ( iii ) with a better quality of walking , than current physiotherapy intervention for non-ambulatory stroke patients . Methods A prospect i ve , r and omised controlled trial of inpatient intervention with a 6 month follow-up with blinded assessment will be conducted . 130 stroke patients who are unable to walk independently early after stroke will be recruited and r and omly allocated to a control group or an experimental group . The control group will undertake 30 min of routine assisted overground walking while the experimental group will undertake 30 min of treadmill walking with partial weight support via an overhead harness per day . The proportion of participants achieving independent walking , the quality of walking , and community participation will be measured . The study has obtained ethical approval from the Human Research Ethics Committees of each of the sites involved in the study . Discussion Given that the Australian population is ageing and people after stroke can expect to live for longer , attainment of safe , independent walking is more likely to be associated with long-term health and well being . In its National Research Priorities , the Government has recognised that it will be important to promote healthy ageing and that this endeavour will be underpinned by research . The results of this study will clearly identify effective intervention to establish early quality walking , thereby promoting an increase in community participation in the longer term . Trial Registration The protocol for this study is registered with US NIH Clinical trials registry ( NCT00167531 The prevention of injury associated with falls in older people is a public health target in many countries around the world . Although there is good evidence that interventions such as multifactorial fall prevention and individually prescribed exercise are effective in reducing falls , the effect on serious injury rates is unclear . Historically , trials have not been adequately powered to detect injury endpoints , and variations in case definition across trials have hindered meta- analysis . It is possible that fall-prevention strategies have limited effect on falls that result in injuries or are ineffective in population s who are at a higher risk of injury . Further research is required to determine whether fall-prevention interventions can reduce serious injuries . Prevention of Falls Network Europe ( ProFaNE ) is a collaborative project to reduce the burden of fall injury in older people through excellence in research and promotion of best practice ( www.profane.eu.org ) . The European Commission funds the network , which links clinicians , members of the public , and research ers worldwide . The aims are to identify major gaps in knowledge in fall injury prevention and to facilitate the collaboration necessary for large-scale clinical research activity , including clinical trials , comparative research , and prospect i ve meta- analysis . Work is being undertaken in a 4-year program . As a first step , the development of a common set of outcome definitions and measures for future trials or meta- analysis was considered Background and Purpose : This study sought to evaluate early supported discharge and continued rehabilitation at home after stroke , at a minimum of 6 months after the intervention , in terms of patient outcome , re source use and health care cost . Methods : Eighty-three patients , moderately impaired 5–7 days after acute stroke , were included in a r and omized controlled trial , 42 being allocated to the intervention and 41 to routine rehabilitation . One-year follow-up of patient outcome included mortality , motor capacity , dysphasia , activities of daily living , social activities , perceived dysfunction , and self-reported falls . Re source use over 12 months included inpatient hospital care , outpatient health care , use of health-related services , informal care , and cost of health care . Results : On univariate analysis there was no difference in patient outcome . Multivariate regression analysis showed that intervention had a significant effect on independence in activities of daily living . A significant difference in inpatient hospital care , initial and recurrent , was observed , with a mean of 18 ( intervention ) versus 33 days ( control ) ( p = 0.002 ) . Further significant differences were that the control group registered more outpatient visits to hospital occupational therapists ( p = 0.02 ) , private physical therapists ( p = 0.03 ) and day-hospital attendance ( p = < 0.001 ) , while the intervention group registered more visits to nurses in primary care ( p = 0.03 ) and home rehabilitation ( p = < 0.001 ) . Other differences in outcomes or re source utilization were nonsignificant . Conclusion : In Sweden , early supported discharge with continued rehabilitation at home proved no less beneficial as a rehabilitation service , and provided care and rehabilitation for 5 moderately disabled stroke patients over 12 months after stroke onset for the cost of 4 in routine rehabilitation OBJECTIVE Vitamin D supplementation is suggested to reduce the risk of falls among ambulatory or institutionalized elderly subjects . The present study was undertaken to address the reduced risk of falls and hip fractures in patients with long-st and ing stroke by vitamin D supplementation . METHODS Ninety-six elderly women with poststroke hemiplegia were followed for two years . Patients were r and omly assigned to one of the two groups , and 48 patients received 1,000 IU ergocalciferol daily , and the remaining 48 received placebo . The number of falls per person and incidence of hip fractures were compared between the two groups . Strength and tissue ATPase of skeletal muscles on the nonparetic side were assessed before and after the study . RESULTS At baseline , serum 25-hydroxyvitamin D levels were in the deficient range ( < 10 ng/ml ) in all patients ; and vitamin D treatment enhanced serum 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels . Vitamin D treatment accounted for a 59 % reduction in falls ( 95 % CI , 28 - 81 % ; p = 0.003 ) . There were increases in the relative number and size of type II muscle fibers and improved muscle strength in the vitamin D-treated group . Hip fractures occurred in 4 of 48 placebo group and 0 in 48 vitamin D2 group during the 2-year study period ( log-rank , p = 0.049 ) . CONCLUSION Vitamin D may increase muscle strength by improving atrophy of type II muscle fibers , which may lead to decreased falls and hip fractures Although vitamin D supplementation has been suggested to reduce the risk of falling in ambulatory or institutionalized elderly persons , no study has examined whether it reduces the frequency of falling in immobilized stroke patients who have immobilization-induced hypercalcemia reflecting increased bone resorption leading to inhibited renal synthesis of 1 , 25-dihydroxyvitamin D ( 1 , 25-[OH]2D ) . Bisphosphonate is known to reduce immobilization-induced hypercalcemia by inhibiting bone resorption of calcium . This study compared the efficacy of 2 drugs in reducing the risk of falling in patients with long-st and ing stroke . Eighty-two elderly patients with poststroke hemiparesis were followed for 1 year . The patients were r and omly assigned to one of 2 groups ; 41 patients received alendronate 35 mg once weekly , and 41 patients received alphacalcidiol 1 μg daily . The number of falls per person and incidence of hip fracture in the 2 groups were compared . At baseline , all patients had a low serum 1 , 25-[OH]2D level . Alphacalcidol therapy enhanced immobilization-induced hypercalcemia by increasing intestinal calcium absorption , leading to a reduction of serum 1 , 25-[OH]2D level , while alendronate therapy enhanced 1 , 25-[OH]2D production by decreasing hypercalcemia . Alendronate treatment accounted for a 55 % reduction in falls ( 95 % confidence interval [CI]=25 - 72 % ; P=.0021 ) . During the 1-year study period , hip fracture occurred in 1 of 41 subjects in the alphacalcidol group and in no subjects in the alendronate group . Bone mineral density was increased by 3.2 % in the alendronate group and decreased by 0.1 % in the alphacalcidol group ( P<.0001 ) . Alendronate therapy increased serum 1 , 25-[OH]2D levels by improving immobilization-induced hypercalcemia , which may lead to decreased falling and subsequent hip fractures BACKGROUND There is a high incidence of hip fractures in patients with hemiplegic stroke . Bone mineral density ( BMD ) is decreased in the hemiplegic side in patients after stroke , correlating with the degree of paralysis and of hypovitaminosis D. OBJECTIVE To evaluate the efficacy of risedronate in reducing the severity of osteoporosis and in decreasing the risk of hip fractures in elderly women following an acute stroke . METHODS This was a 12-month , r and omized , double blind , placebo-controlled trial . In a prospect i ve study of stroke patients , 187 patients received a daily dose of 2.5 mg risedronate for 12 months , and the remaining 187 received placebo . Incidence of hip fracture was compared between the two groups at the endpoint of the study . RESULTS Seven patients sustained hip fractures on the hemiplegic side in the placebo group , and one hip fracture occurred in the risedronate group ( p = 0.0360 ; OR = 7.0 ) . BMD increased by 1.5 % and decreased by 4.9 % in the risedronate group and placebo group ( p < 0.0001 ) . Urinary deoxypyridinoline , a bone resorption marker , decreased by 53.4 % in the risedronate group and increased by 35.8 % in the placebo group . CONCLUSION Treatment with risedronate increases bone mineral density in elderly women following an acute stroke and prevents hip fractures BACKGROUND Early supported discharge ( ESD ) with continued rehabilitation at home has shown a beneficial effect on extended activities of daily living 5 years after stroke . The long-term effect of ESD on re source use has not been explored . METHODS At 5 years , 54 patients with mild to moderate disability , enrolled in a r and omized controlled trial of ESD , were followed up . Data were collected from a county register and by interviewing the patient or the patient 's spouse . RESULTS There were differences in mean length of hospitalization , 51 versus 32 days ( P = .02 ) . There was no significant difference between the groups in regard to total outpatient rehabilitation , ESD visits included , but there was a difference in where the services were obtained . The ESD group had more rehabilitation at home ( ESD service ) and the control group had more outpatient rehabilitation ( P = .04 ) , including physiotherapy in primary care ( P = .05 ) . There were no other differences . CONCLUSION We conclude that , 5 years after stroke , our ESD service was favorable with regard to re source use OBJECTIVE To examine the effect of a 12-week Tai Chi ( TC ) intervention on physical function and quality of life . DESIGN Single-blind , r and omized controlled trial . SETTING General community . PARTICIPANTS Community-dwelling survivors of stroke ( N=145 ; 47 % women ; mean age , 70y ; time poststroke : 3y ; ischemic stroke : 66 % ; hemiparesis : 73 % ) who were aged ≥50 years and were ≥3 months poststroke . INTERVENTIONS Yang style 24-posture short-form TC ( n=53 ) , strength and range of movement exercises ( SS ) ( n=44 ) , or usual care ( UC ) ( n=48 ) for 12 weeks . The TC and SS groups attended a 1-hour class 3 times per week , whereas the UC group had weekly phone calls . MAIN OUTCOME MEASURES Physical function : Short Physical Performance Battery , fall rates , and 2-minute step test ; quality of life : Medical Outcomes Study 36-Item Short-Form Health Survey , Center for Epidemiologic Studies Depression Scale , and Pittsburgh Sleep Quality Index . RESULTS During the intervention , TC participants had two thirds fewer falls ( 5 falls ) than the SS ( 14 falls ) and UC ( 15 falls ) groups ( χ(2)=5.6 , P=.06 ) . There was a significant group by time interaction for the 2-minute step test ( F2,142=4.69 , P<.01 ) . Post hoc tests indicated that the TC ( t53=2.45 , P=.02 ) and SS ( t44=4.63 , P<.01 ) groups had significantly better aerobic endurance over time , though not in the UC group ( t48=1.58 , P=.12 ) . Intervention adherence rates were 85 % . CONCLUSIONS TC and SS led to improved aerobic endurance , and both are suitable community-based programs that may aid in stroke recovery and community reintegration . Our data suggest that a 12-week TC intervention was more effective in reducing fall rates than SS or UC interventions . Future studies examining the effectiveness of TC as a fall prevention strategy for community-dwelling survivors of stroke are recommended Objective : To assess the feasibility of conducting a r and omized controlled trial of occupational therapy predischarge home visits for people after stroke . Design : R and omized controlled trial and cohort study . We r and omized eligible patients for whom there was clinical uncertainty about the need to conduct a home visit to a r and omized controlled trial ; patients for whom a visit was judged ‘ essential ’ were enrolled into a cohort study . Setting : Stroke rehabilitation unit of teaching hospital . Participants : One hundred and twenty-six participants hospitalized following recent stroke . Interventions : Predischarge home visit or structured , hospital-based interview . Main outcome measures : The primary objective was to collect information on the feasibility of a r and omized controlled trial , including eligibility , control intervention and outcome assessment s. The primary outcome measure was the Nottingham Extended Activities of Daily Living Scale at one month after discharge from hospital . Secondary outcomes included mood , quality of life and costs at one week and one month following discharge . Results : Ninety-three people were allocated to the r and omized controlled trial ; 47 were r and omized to intervention and 46 to control . Thirty-three were enrolled into the cohort study . More people were allocated to the r and omized controlled trial as the study progressed . One hundred and thirteen people ( 90 % ) received the proposed intervention , although there was a need for stricter protocol adherence . Follow-up was good : at one month 114 ( 90 % ) were assessed . There were no significant differences between the groups in the r and omized controlled trial for the primary outcome measure at one month . The average cost of a home visit was £ 208 . Conclusion : A trial is feasible and warranted given the re source implication s of predischarge occupational therapy home visits BACKGROUND The common use of physical restraints in older people in hospitals and nursing homes has been associated with injurious falls , decreased mobility and disorientation . By offering access to bed-chair pressure sensors in hospitalized patients with perceived fall risk , nurses may be less inclined to resort to physical restraints , thereby improving clinical outcomes . AIMS AND OBJECTIVES To investigate whether the access of bed-chair pressure sensors reduces physical restraint use in geriatric rehabilitation wards . DESIGN R and omized controlled trial . METHODS Consecutively , patients admitted to two geriatric wards specialized in stroke rehabilitation in a convalescent hospital in Hong Kong , and who were perceived by nurses to be at risk of falls were r and omly assigned to intervention and control groups . For the intervention group subjects , nurses were given access to bed-chair pressure sensors . These sensors were not available to control group subjects , as in usual practice . The trial continued until discharge . The primary outcomes were the proportion of subjects restrained by trunk restraint , bedrails or chair-board and the proportion of trial days in which each type of physical restraint was applied . The secondary outcomes were the proportions of those who improved in the mobility and transfer domains of modified Barthel index on discharge and of those who fell . RESULTS One hundred and eighty subjects were r and omized . Fifty ( 55.6 % ) out of the 90 intervention group subjects received the intervention . There was no significant difference between the intervention and control groups in the proportions and duration of having the three types of physical restraints . There was also no group difference in the chance of improving in mobility and transfer ability , and of having a fall . CONCLUSION Access to bed-chair pressure sensor device neither reduced the use of physical restraints nor improved the clinical outcomes of older patients with perceived fall risk . RELEVANCE TO CLINICAL PRACTICE The provision of bed-chair pressure sensors may only be effective in reducing physical restraints when it is combined with an organized physical restraint reduction programme Background and Objective : Previous clinical studies have shown that Neuroaid ( MLC 601 ) may be beneficial in post-stroke rehabilitation . Our aim was to investigate the efficacy of Neuroaid on motor recovery in ischemic stroke patients using rehabilitation endpoints in accordance with the International Conference on Harmonization/Good Clinical Practice guidelines , in order to provide predictive information for further larger trials . Methods : This is a phase II double-blind , placebo-controlled pilot study of 40 subjects admitted with a recent ( less than 1 month ) ischemic stroke . All subjects were given either Neuroaid or placebo , 4 capsules 3 times a day for 4 weeks . Fugl-Meyer Assessment ( FMA ) , National Institutes of Health Stroke Scale and Functional Independence Measure scores were measured at initiation of the treatment , and at 4 and 8 weeks . Results : None of the outcomes was statistically significant between the two groups . However , FMA scores showed a positive trend for improvement with Neuroaid treatment over time . Subgroup analysis of subjects with posterior circulation infa rct ion and severe stroke both showed a tendency for better recovery . Conclusion : Some positive trends were observed in the Neuroaid group . A larger multicenter trial focusing on severe stroke patients is needed to better evaluate the role of Neuroaid in aiding stroke recovery in rehabilitation Objective : To evaluate the effects of a new , individually adjusted , progressive and specific balance group training programme on fear of falling , step execution , and gait in healthy elderly people with fear of falling and tend to fall . Design : R and omized controlled trial . Setting : The study was conducted in Stockholm County , Sweden . Subjects : Fifty-nine community dwelling elderly people were recruited by advertisement , and allocated at r and om to an intervention group ( n = 38 ) or a control group ( n = 21 ) . Intervention : Individually adjusted , progressive and specific balance group training was given three times a week for three months . The training incorporated elements included in , and required for , independent activities of daily living , and for reactions to loss of balance during dual or multiple tasks . Main measures : Fear of falling was assessed with Falls Efficacy Scale International ( FES-I ) . The reaction time of step execution was measured with the step-execution test , and gait was measured with GAITRite ® . Results : After three months the intervention group showed significant positive changes in the FES-I ( P = 0.008 ) , in the step-execution phase of dual-task performance ( P = 0.012 ) , and in gait at preferred speed during single-task performance ; in cadence ( P = 0.030 ) and , at fast speed , in velocity ( P = 0.004 ) and cadence ( P = 0.001 ) . Significant decreases were also found for the likelihood of depression after participating in the training programme . Conclusion : This new balance training programme is feasible and leads to decreased fear of falling , decreased time for step execution during dual-task performance and increased velocity during fast walking OBJECTIVE To determine the role of symmetrical body-weight distribution training in preventing falls among patients with hemiplegic stroke . DESIGN A prospect i ve study using a st and ing biofeedback trainer . SETTING Hospital-based rehabilitation units . PATIENTS Fifty-four patients with hemiplegic stroke ( 30 in the training group , 24 in the control group ) . INTERVENTIONS Conventional stroke rehabilitation program , plus symmetrical st and ing training and repetitive sit-to-st and training , with a st and ing biofeedback trainer . Training effect was evaluated by assessing the sit-to-st and performance and comparing the occurrence of falls in the 2 groups at a 6-month follow-up . MAIN OUTCOME MEASURES Occurrence of falls , sit-to-st and performance , including body-weight distribution , rate of rise in force , and sway in center of pressure ( COP ) . RESULTS Significant improvement in sit-to-st and performance was found in patients in the training group . Body weight was distributed more symmetrically in both legs , with less mediolateral sway in the COP when rising and sitting down . The mean difference in body-weight distribution between the left and right legs while subjects were rising from a chair significantly decreased , from 49.5 % + /- 18.9 % to 38.6 % + /- 15.8 % of body weight ( BW ) ( p < .005 ) . The rate of rise in force while rising from a chair significantly increased , from 28.3 % + /- 13.5%BW/s to 53.6 % + /- 20.5%BW/s ( p < .001 ) . At the 6-month follow-up , 10 of 24 patients ( 41.7 % ) in the control group had fallen , compared with only 5 of 30 patients ( 16.7 % ) in the training group ( p < .05 ) . CONCLUSIONS Symmetrical body-weight distribution training may improve sit-to-st and performance and , consequently , decrease the number of falls by stroke patients Background and aims : Falls are particularly common among older people living in residential care facilities . The aim of this r and omized controlled trial was to evaluate the effectiveness of a high-intensify functional exercise program in reducing falls in residential care facilities . Methods : Participants comprised 191 older people , 139 women and 52 men , who were dependent in activities of daily ) living . Their mean±SD score on the Mini-Mental State Examination was 17.8±5.1 ( range 10–30 ) . Participants were r and omized to a high-intensity functional exercise program or a control activity , consisting of 29 sessions over 3 months . The fall rate and proportion of participants sustaining a fall were the outcome measures , subsequently analysed using negative binominal analysis and logistic regression analysis , respectively . Results : During the 6-month follow-up period , when all participants were compared , no statistically significant differences between groups were found for fall rate ( exercise group 3.6 falls per person years [ PY ] , control group 4.6 falls per PY ) , incidence rate ratio ( 95 % CI ) 0.82 ( 0.49−1.39 ) , p=0.46 , or the proportion of participants sustaining a fall ( exercise 53 % , control 51 % ) , odds ratio ( 95 % CI ) 0.95 ( 0.52−1.74 ) , p=0.86 . A subgroup interaction analysis revealed that , among participants who improved their balance during the intervention period , the exercise group had a lower fall rate than the control group ( exercise 2.7 falls per PY , control 5.9 falls per PY ) , incidence rate ratio ( 95 % CI ) 0.44 ( 0.21−0.91 ) , p=0.03 . Conclusions : In older people living in residential care facilities , a high-intensity functional exercise program may prevent falls among those who improve their balance Objective : Examine the safety and feasibility of a 12-week Tai Chi intervention among stroke survivors . Design : Two-group , prospect i ve pilot study with r and om allocation . Setting : Outpatient rehabilitation facility . Subjects : Stroke survivors ≥50 years and at ≥three months post-stroke . Interventions : Tai Chi subjects attended group-based Yang Style classes three times/week for 12-weeks , while Usual Care subjects received weekly phone calls along with written material s/re sources for participating in community-based physical activity . Main outcome measures : Indicators of study safety and feasibility included recruitment rates , intervention adherence , falls or adverse events , study satisfaction , drop-outs , and adequacy of the outcomes measures . Results : Interested persons pre-screened by phone ( n = 69 ) were on average 68 years old , ( SD = 13 ) years old , 48 % ( n = 33 ) women , 94 % ( n = 65 ) were at least three months post-stroke . A total of 28 subjects aged 69 ( SD = 11 ) years enrolled in this pilot study . Intervention adherence rates were very high ( ≥92 % ) . There were no falls or other adverse events . The dose of Tai Chi exercise ( ≥150 minutes/week ) was well tolerated . Overall study satisfaction was high ( 8.3 ( SD = 1.9 ) ; 1 = not satisfied , 10 = most satisfied ) , while drop-outs ( n = 3 , 11 % ) were unrelated to study intervention . Score distributions for the outcome measures were approximately normal , sensitive to change , and seemed to favor the Tai Chi intervention . Conclusions : Tai Chi is a safe , community-based exercise program for stroke survivors . Our data suggest that recruitment and retention of an adequate sample is feasible , and that in a full-scale study 52 subjects/group are needed to detect statistically significant between group differences ( alpha = 0.05 , power = 0.80 ) BACKGROUND AND PURPOSE We sought to observe the type , timing , and frequency of complications occurring in hospitalized patients after an acute stroke . METHODS In a single hospital , we prospect ively identified a consecutive cohort of patients who were either admitted after an acute stroke or who suffered a stroke while already an inpatient ( n=613 ) . We retrieved the case notes for 607 ( 99 % ) of these strokes , and a single observer , using predefined diagnostic criteria , review ed the notes and recorded the type , timing , and frequency of complications that occurred during the inpatient period . We also measured the reliability of complication identification from case note review by comparing two observers on a sample of records . RESULTS Complications were recorded after 360 strokes ( 59 % ) ; the most common individual complications were falls ( complicating 22 % of all strokes ) , skin breaks ( 18 % ) , and urinary tract ( 16 % ) or chest ( 12 % ) infections . Miscellaneous " other " complications complicated 32 % of strokes . Seizures and chest infections occurred early , whereas depression and painful shoulder were later problems . Complications were more common in older patients , who were more disabled before their stroke and had suffered more severe strokes . We demonstrated moderate to good agreement between the two observers for most complications . CONCLUSIONS Complications after acute stroke are common , confirming that stroke rehabilitation requires active and knowledgeable medical input . Knowing the nature and timing of complications , together with the identification of high-risk patients , may be useful to those planning stroke services . The differences in our results and those previously reported , most notably for skin breaks , are probably due to the different methods used , in particular patient selection and diagnostic criteria for complications . Although complications may be useful as a measure of outcome in comparative studies ( eg , therapeutic trials and audit ) , the method ological difficulties in accurately and reliably measuring them must be addressed Objective : This study compared two modes of physiotherapy service over 12 months in community-dwelling people with stroke , either following a train — wait train paradigm by providing bouts of intense physiotherapy , or a continuous less intense programme . Design : R and omized trial . Setting : Community-dwelling people with stroke . Interventions : Fifty patients , first-time stroke , discharged home , following inpatient rehabilitation , allocated to two groups , A and B. Over 12 months , Group A ( n = 25 ) received three two-month blocks of therapy at home , each block contained four 30 to 45 minute sessions per week , totalling 96 sessions . Group B ( n = 25 ) continuously received two 30 to 45 minute sessions per week , totalling 104 sessions . Main outcome measures : Primary Rivermead Mobility Index ( 0—15 ) , secondary upper- and lower-limb motor functions , Activities of Daily Living competence , tone and number of falls . Results : Both groups were comparable at onset , the mean age in Group A ( B ) was 62.4 ( 61.9 ) years . A and B patients equally improved functions over time , between group differences did not occur . The initial ( terminal ) Rivermead Mobility Index was 9.4 ± 2.8 ( 12.2 ± 2.1 ) in Group A , and 8.5 ± 3.5 ( 11.2 ± 2.7 ) in Group B. More Group B patients fell seriously ( 7 versus 1 ) . Conclusions : The intermittent high-intensity and continuous low-intensity therapy protocol s were equally effective , the sheer intensity seems more important than the time-mode of application . The relatively young patients functionally improved in the first year after stroke , the reduced risk of serious falls in the intermittent high-intensity group should be vali date We r and omly assigned 39 patients with stroke and homonymous hemianopia or unilateral visual neglect to treatment with 15-diopter plastic press-on Fresnel prisms ( n = 18 ) or to serve as controls ( n = 21 ) . Baseline evaluations of visual perception and activities-of-daily-living ( ADL ) function were similar for both groups . After 4 weeks , the prism-treated group performed significantly better than controls on the following : ( 1 ) Motor Free Visual Perception Test ; ( 2 ) Line Bisection Task ; ( 3 ) Line Cancellation Task ; ( 4 ) Harrington Flocks Visual Field Screener ; and ( 5 ) Tangent Screen Examination . There was no significant difference in Barthel ADL assessment at 4 weeks . Thus , treatment with 15-diopter Fresnel prisms improves visual perception test scores but not ADL function in stroke patients with homonymous hemianopia or unilateral visual neglect PURPOSE Whole-body vibration therapy has gained increasing popularity in enhancing neuromotor function in various patient population s. It remains uncertain , however , whether whole-body vibration is beneficial when used in stroke patients . The aim of this r and omized controlled trial was to examine the efficacy of whole-body vibration in optimizing neuromotor performance and reducing falls in chronic stroke patients . METHODS Eighty-two chronic stroke patients were r and omly assigned to either the experimental group or control group . The experimental group received 9 - 15 min of whole-body vibration ( vertical vibration ; frequency = 20 - 30 Hz . amplitude = 0.44 - 0.60 mm , peak acceleration = 9.5 - 15.8 m·s or 0.97 - 1.61 U of Earth gravitational acceleration ( g ) while performing a variety of dynamic leg exercises on the vibration platform . The control group performed the same exercises without vibration . The subjects underwent their respective training three times a week for 8 wk . Balance ( Berg balance scale ) , mobility ( 10-m walk test and 6-min walk test ) , knee muscle strength ( isokinetic dynamometry ) , and fall-related self-efficacy ( activities-specific balance confidence scale ) were assessed at baseline , immediately after the 8-wk training and at a 1-month follow-up . The incidence of falls was recorded until 6 months after the termination of training . RESULTS Intention-to-treat analysis revealed similar significant improvement in all balance , mobility , muscle strength , and fall-related self-efficacy measures in both groups after the 8-wk treatment period ( P < 0.001 ) , and these were maintained at the 1-month follow-up . The incidence of falls did not differ significantly between the two groups ( P > 0.05 ) . CONCLUSIONS The addition of the presently used whole-body vibration paradigm to a leg exercise protocol was no more effective in improving neuromotor performance and reducing the incidence of falls than leg exercises alone in chronic stroke patients who have mild to moderate motor impairments OBJECTIVES To determine whether a multifactorial falls prevention program reduces falls in people with stroke at risk of recurrent falls and whether this program leads to improvements in gait , balance , strength , and fall-related efficacy . DESIGN A single blind , multicenter , r and omized controlled trial with 12-month follow-up . SETTING Participants were recruited after discharge from rehabilitation and followed up in the community . PARTICIPANTS Participants ( N=156 ) were people with stroke at risk of recurrent falls being discharged home from rehabilitation . INTERVENTIONS Tailored multifactorial falls prevention program and usual care ( n=71 ) or control ( usual care , n=85 ) . MAIN OUTCOME MEASURES Primary outcomes were rate of falls and proportion of fallers . Secondary outcomes included injurious falls , falls risk , participation , activity , leg strength , gait speed , balance , and falls efficacy . RESULTS There was no significant difference in fall rate ( intervention : 1.89 falls/person-year , control : 1.76 falls/person-year , incidence rate ratio=1.10 , P=.74 ) or the proportion of fallers between the groups ( risk ratio=.83 , 95 % confidence interval=.60 - 1.14 ) . There was no significant difference in injurious fall rate ( intervention : .74 injurious falls/person-year , control : .49 injurious falls/person-year , incidence rate ratio=1.57 , P=.25 ) , and there were no significant differences between groups on any other secondary outcome . CONCLUSIONS This multifactorial falls prevention program was not effective in reducing falls in people with stroke who are at risk of falls nor was it more effective than usual care in improving gait , balance , and strength in people with stroke . Further research is required to identify effective interventions for this high-risk group Background and Purpose — Falls are an important issue in older people . We aim ed to determine the incidence , circumstances , and predictors of falls in patients with recent acute stroke . Methods — The Auckl and Regional Community Stroke ( ARCOS ) study was a prospect i ve population -based stroke incidence study conducted in Auckl and , New Zeal and ( NZ ) during 2002 to 2003 . Among 6-month survivors , the location and consequences of any falls were ascertained by self-report as part of a structured interview . Multivariable logistic regression was used to establish associations between risk factors and “ any ” and “ injurious ” falls . Results — Of 1104 stroke survivors who completed an interview , 407 ( 37 % ) reported at least 1 fall , 151 ( 37 % of fallers , 14 % of stroke survivors ) sustained an injury that required medical treatment , and 31 ( 8 % of fallers , 3 % of stroke survivors ) sustained a fracture . The majority of falls occurred indoors at home . Independent factors associated with falls were depressive symptoms , disability , previous falls , and older age . For injurious falls , the positively associated factors were female sex and NZ/European ethnicity and dependence before the stroke , whereas higher levels of activity and normal cognition were negatively associated factors . Conclusions — Falls are common after stroke , and their predictive factors are similar to those for older people in general . Falls prevention programs require implementation in stroke services Background : Interventions that may reduce the number and severity of potentially harmful post-stroke complications are desirable . This study explored whether very early and frequent mobilisation ( VEM ) affected complication type ( immobility/stroke related ) , number and severity . Methods : Secondary analysis from phase II , r and omised controlled trial . Patients admitted within 24 h of stroke , whose physiological parameters fell within set limits , were r and omised to either VEM , commencing < 24 h , or st and ard care . Complications to 3 months were recorded by a blinded assessor and classified by a neurologist . Analysis was intention to treat . Results : Seventy-one patients were recruited ( st and ard care 33 ; VEM 38).There were no significant group differences in the number , type or severity of complications by 3 months , and most patients ( 81.6 % ) experienced one or more complications . Falls were common , while depression was absent . The multivariate analysis showed older age ( OR 1.10 , 95 % CI : 1.02–1.18 , p = 0.009 ) and longer length of stay ( OR 1.18 , 95 % CI : 1.06–1.32 , p = 0.002 ) were associated with experiencing an immobility-related complication . Conclusion : Interventions that promote recovery and reduce complications may consequently reduce length of stay . The larger phase III trial currently underway may shed light on whether increasing mobilisation reduces complications after stroke |
13,857 | 25,058,164 | In all but one study , third tier ( very low quality ) evidence indicated that lidocaine was better than placebo for some measure of pain relief .
Pooling multiple-dose studies across conditions demonstrated no clear evidence of an effect of lidocaine on the incidence of adverse events or withdrawals , but there were few events and the withdrawal phase of enriched enrolment design s is not suitable to assess the true impact of adverse events ( very low quality evidence ) .
This review found no evidence from good quality r and omised controlled studies to support the use of topical lidocaine to treat neuropathic pain , although individual studies indicated that it was effective for relief of pain .
Clinical experience also supports efficacy in some patients . | BACKGROUND Lidocaine is a local anaesthetic that is sometimes used on the skin to treat neuropathic pain .
OBJECTIVES To assess the analgesic efficacy of topical lidocaine for chronic neuropathic pain in adults , and to assess the associated adverse events . | Background : Evidence -based pharmacological treatment options for patients with persistent inguinal postherniorrhaphy pain are lacking . Methods : Twenty-one male patients , with severe , unilateral , persistent inguinal postherniorrhaphy pain , participated in a r and omized , double-blind , placebo-controlled crossover trial , receiving lidocaine patch ( 5 % ) and placebo patch treatments in periods of 14 days separated by a 14-day wash-out period . Pain intensities ( at rest , during movement , and pressure evoked [ Numerical Rating Scale ] ) were assessed before treatment and on the last 3 days of each treatment period . Patients were a priori divided into two subgroups based on quantitative sensory testing ( + /− thermal “ hyposensitivity ” ) . Skin biopsies for intraepidermal nerve fiber density assessment were taken at baseline , and quantitative sensory testing was performed before and after each treatment period . The primary outcome was change in pain intensity assessed as the difference in summed pain intensity differences between lidocaine and placebo patch treatments . Results : There was no difference in summed pain intensity differences between lidocaine and placebo patch treatments in all patients ( mean difference 6.2 % [ 95 % CI = −6.6 to 18.9 % ] ; P = 0.33 ) or in the two subgroups ( + /− thermal “ hyposensitivity ” ) . The quantitative sensory testing ( n = 21 ) demonstrated an increased pressure pain thresholds after lidocaine compared with placebo patch treatment . Baseline intraepidermal nerve fiber density ( n = 21 ) was lower on the pain side compared with the nonpain side ( −3.8 fibers per millimeter [ 95 % CI = −6.1 to −1.4 ] ; P = 0.003 ) . One patient developed mild erythema in the groin during both treatments . Conclusions : Lidocaine patch treatment did not reduce combined resting and dynamic pain ratings compared with placebo in patients with severe , persistent inguinal postherniorrhaphy pain Objective Oral amitriptyline , a tricyclic antidepressant , is effective for treating neuropathic pain . We conducted a double-blind , r and omized , placebo-controlled crossover study to evaluate the efficacy of topical 5 % amitriptyline and 5 % lidocaine in treating patients with neuropathic pain . Methods Thirty-five patients with postsurgical neuropathic pain , postherpetic neuralgia , or diabetic neuropathy with allodynia or hyperalgesia were assigned to receive 3 topical creams ( 5 % amitriptyline , 5 % lidocaine , or placebo ) in r and om sequence . The primary outcome measure was change in pain intensity ( baseline vs. posttreatment average pain ) using a 0 to 100 mm Visual Analog Scale . Secondary outcome measures included the McGill Pain Question naire , requirement for rescue medication , and patient satisfaction . Primary statistical comparisons were made with paired t tests or signed-rank tests . Results A reduction in pain intensity was observed with topical lidocaine ( P<0.05 ) . No significant change in pain intensity was found with topical amitriptyline or placebo . In pairwise comparison of treatments , topical lidocaine and placebo each reduced pain more than topical amitriptyline ( P<0.05 ) . Discussion This r and omized , placebo-controlled crossover study examining topical 5 % amitriptyline and 5 % lidocaine in the treatment of neuropathic pain showed that topical lidocaine reduced pain intensity but the clinical improvement is minimal and that topical 5 % amitriptyline was not effective 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 Objective Current therapies often have limited efficacy and untenable side effects when used to treat persistent incisional pain following cancer-related surgery . Lidocaine patches reduce neuropathic pain from herpes zoster but their benefits for persistent cancer-related postsurgical incisional pain remain unclear . Study design Multicenter , double-blind , r and omized , two-period crossover trial . Material s and methods Twenty-eight cancer patients with postsurgical incisional pain were r and omly assigned to receive either lidocaine patches followed by placebo patches or the reverse . Each study period lasted 4 weeks . Patches were applied daily upon waking and left in place for a maximum of 18 h. The primary outcome measure , an 11-point pain intensity rating scale , was administered weekly . Secondary outcomes were administered weekly ( Brief Pain Inventory-Short Form(BPI-SF ) , Subject Global Impression of Change ) and at the end of each study period ( Short Form-Magill Pain Question naire , Linear Analogue Self Assessment Scale , Neuropathy Pain Scale , Pain Catastrophizing Scale , Profile of Mood States Short Form ) . Results Twenty-one patients completed the first period and 18 completed their crossover second phase . No significant intergroup differences were detected in pain intensity ratings . Few secondary end points were significantly different when subjects used the lidocaine versus placebo patches . BPI-SF interference scores were lower in patients using the lidocaine patch during the first study period , including several scores that achieved statistical significance , general activity ( p = 0.02 ) , work ( p = 0.04 ) , and relations with others ( p = 0.02 ) . Conclusion Lidocaine patch use did not significantly reduce pain intensity ratings or the majority of related secondary end points in cancer patients with persistent incisional pain & 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 BACKGROUND Traditional and largely qualitative review s of evidence are now giving way to much more structured systematic overviews that use a quantitative method to calculate the overall effect of treatment . The latter approach is dependent on the quality of primary studies , which may introduce bias if they are of poor method ologic quality . OBJECTIVE To test the hypothesis that the inclusion of poor- quality trials in meta-analyses would bias the conclusions and produce incorrect estimates of treatment effect . METHODS An overview of r and omized trials of antiestrogen therapy in subfertile men with oligospermia was performed to test the hypothesis . Data sources included online search ing of MEDLINE and Science Citation Index data bases between 1966 and 1994 , scanning the bibliography of known primary studies and review articles , and contacting experts in the field . After independent , blind assessment , nine of 149 originally identified studies met the inclusion criteria and were selected . We assessed study quality independently . Outcome data from each study were pooled and statistically summarized . RESULTS There was a marginal improvement in pregnancy rate with antiestrogen treatment ( odds ratio , 1.6 ; 95 % confidence interval , 0.9 to 2.6 ) . Sensitivity analyses on the basis of method ologic quality demonstrated that poor- quality studies produced a positive effect with treatment , whereas no benefit was observed with high- quality studies . CONCLUSION The results of a meta- analysis are influenced by the quality of the primary studies included . Method ologically , poor studies tend to exaggerate the overall estimate of treatment effect and may lead to incorrect inferences Postherpetic neuralgia ( PHN ) following herpes zoster is a common and disabling neuropathic pain syndrome . In a double‐blind , three‐session study , 5 % lidocaine gel or vehicle was applied simultaneously to both the area of pain and to the contralateral mirror‐image unaffected skin . In the local session , lidocaine gel was applied to the painful skin area . In the remote session , lidocaine gel was applied to mirror‐image skin . In the placebo session , vehicle was applied bilaterally . For cranial PHN , gel was applied without occlusion for 8 hours . For limb or torso PHN , gel was applied under occlusion for 24 hours . The 16 subjects with cranial PHN reported pain relief significantly favoring local drug application at 30 minutes , 2 , 4 , and 8 hours . The 23 subjects with torso or limb PHN reported significantly lower pain intensity with local drug application at 8 hours and both pain relief and reduced pain intensity at 24 hours . Remote lidocaine application to mirror‐image skin was no different from placebo . No systemic adverse effects were reported and blood levels did not exceed 0.6 μg/ml . Topical application of 5 % lidocaine gel relieves PHN pain by a direct drug action on painful skin BACKGROUND Trigeminal nerve block has been widely used for trigeminal neuralgia . This may induce paraesthesia . The second division of the trigeminal nerve passes through the sphenopalatine ganglion , which is located posterior to the middle turbinate and is covered by a mucous membrane . We examined the effectiveness of intranasal lidocaine 8 % spray on paroxysmal pain in second-division trigeminal neuralgia . METHODS Twenty-five patients with second-division trigeminal neuralgia were r and omized to receive two sprays ( 0.2 ml ) of either lidocaine 8 % or saline placebo in the affected nostril using a metered-dose spray . After a 7 day period , patients were crossed over to receive the alternative treatment . The paroxysmal pain triggered by touching or moving face was assessed with a 10 cm visual analogue scale ( VAS ) before and 15 min after treatment . Patients used a descriptive scale to grade pain outcome , and were asked to note whether the pain returned and how long after therapy it recurred . RESULTS Intranasal lidocaine 8 % spray significantly decreased VAS [ baseline : 8.0 ( 2.0 ) cm , 15 min postspray : 1.5 ( 1.9 ) cm , mean ( SD ) ] , whereas the placebo spray did not [ 7.9 ( 2.0 ) cm , 7.6 ( 2.0 ) cm ] . Moreover , pain was described as moderate or better by 23 patients of the lidocaine spray and 1 of the placebo group . The effect of treatment persisted for 4.3 h ( range 0.5 - 24 h ) . CONCLUSIONS Intranasal lidocaine 8 % administered by a metered-dose spray produced prompt but temporary analgesia without serious adverse reactions in patients with second-division trigeminal neuralgia BACKGROUND : A topical lidocaine patch is effective in the treatment of posttraumatic peripheral neuropathy ( PTPN ) , but it is not suited for breakthrough pain because of difficulty with an additional application . Here , we examined the effect of 8 % lidocaine pump spray ( Xylocaine pump spray ® , XPS ) on peripheral neuropathic pain caused by surgery or injury . METHODS : Thirty-one patients with PTPN were r and omized to receive either XPS or saline placebo pump spray applied to painful skin areas . The optimal dose of up to 30 sprays ( 0.1 mL/single spray , 30 times ) was individually determined as the dose which completely covered the painful site . After a 7-day period , the patients were crossed over to receive the optimal dose of the alternative spray . Pain was assessed with a visual analog scale . RESULTS : XPS , but not placebo pump spray , significantly decreased the visual analog scale for continuing pain and tactile allodynia . The effect persisted for a median of 5 h ( range , 2–60 h ) after application . Mild side effects were reported in three patients with XPS consisting of local irritation ( n = 3 ) and local flare ( n = 1 ) . All adverse events disappeared without medication within a few hours . CONCLUSIONS : The present study suggests that XPS provides a significant improvement in PTPN due to its prompt analgesia , lack of systemic side effects and convenience Topical lidocaine has been recently marketed as a new treatment for post-herpetic neuralgia . The aim of our study was to characterize the absorption profile of and systemic exposure to lidocaine from patch and gel formulations in normal volunteers , patients with post-herpetic neuralgia , and patients with acute herpes zoster . The bioavailability of lidocaine from the patch formulation averaged 3 % , and was similar after single and repeated doses . Systemic exposure to lidocaine and monoethylglycinexylidide ( MEGX ) , the primary active metabolite of lidocaine , after application of lidocaine gel or patches was minimal in normal volunteers , patients with post-herpetic neuralgia , and patients with acute herpes zoster . Considering the benefit versus risk of topical lidocaine , systemic absorption and toxicity of lidocaine seems not to be a significant risk UNLABELLED Progress in the underst and ing of chronic pain with neuropathic features has been hindered by a lack of epidemiologic research in the general population . The Leeds Assessment of Neuropathic Symptoms and Signs score ( S-LANSS ) was recently vali date d for use in postal surveys , making the identification of pain of predominantly neuropathic origin possible . Six family practice s in 3 UK cities ( Aberdeen , Leeds , and London ) generated a total r and om sample of 6,000 adults . The mailed question naire included demographic items , chronic pain identification , and intensity questions , the S-LANSS , the Level of Expressed Needs question naire , and the Neuropathic Pain Scale . With a corrected response rate of 52 % , the prevalence of any chronic pain was 48 % and the prevalence of pain of predominantly neuropathic origin was 8 % . Respondents with this chronic neuropathic pain were significantly more likely to be female , slightly older , no longer married , living in council rented accommodation , unable to work , have no educational qualifications , and be smokers than all other respondents . Multiple logistic regression modeling found that pain of predominantly neuropathic origin was independently associated with older age , gender , employment ( being unable to work ) , and lower educational attainment . Respondents with this pain type also reported significantly greater pain intensity , higher scores on the NPS , higher levels of expressed need , and longer duration of pain . This is the first estimate of the prevalence and distribution of pain of predominantly neuropathic origin in the general population , using a previously vali date d and reliable data collection instrument . PERSPECTIVE Chronic pain with neuropathic features appears to be more common in the general population than previously suggested . This type of pain is more severe than other chronic pain but distributed similarly throughout sociodemographic groups & NA ; Chronic pain is associated with a range of other problems , including disturbed sleep , depression , anxiety , fatigue , reduced quality of life , and an inability to work or socialise . We investigated whether good symptom control of pain ( using definitions of moderate and substantial benefit ) is associated with improvement in other symptoms . Individual patient data from four r and omised trials in fibromyalgia ( 2575 patients ) lasting 8–14 weeks were used to calculate percentage pain reduction for each completing patient ( 1858 ) , divided into one of five groups according to pain reduction , irrespective of treatment : substantial benefit – ≥50 % pain reduction ; moderate – 30 % to < 50 % ; minimal – 15 % to < 30 % ; marginal – 0 % to < 15 % ; worse – < 0 % ( increased pain intensity ) . We then calculated change from baseline to end of trial for measures of fatigue , function , sleep , depression , anxiety , ability to work , general health status , and quality ‐adjusted life year ( QALY ) gain over a 12‐month period . Substantial and moderate pain intensity reductions were associated with statistically significant reduction from baseline by end of trial in all measures , with values by trial end at or approaching normative values . Substantial pain intensity reduction result ed in 0.11 QALYs gained , and moderate pain intensity reduction in 0.07 QALYs gained over a 12‐month period . Substantial and moderate pain intensity reduction predicts broad beneficial outcomes and improved quality of life that do not occur without pain relief . Pain intensity reduction is a simple and effective predictor of which patients should continue treatment , and which should discontinue and try an alternative therapy & NA ; Peripheral neuropathic pain syndromes ( PNPS ) are difficult to treat because commonly used analgesics are often ineffective when , for example , touch‐evoked allodynia , hyperalgesia , and pain paroxysms are present . To investigate whether lidocaine patch 5 % treatment is also effective in postherpetic neuropathy ( PHN ) and in other PNPS , 40 patients with various forms and localizations of PNPS completed a prospect i ve , r and omized , placebo‐controlled , two‐way , cross‐over study in three medical hospitals . Patients suffering from pain in a localized skin area with intensity above 40 mm visual analog scale ( VAS ) and a stable consumption of pain medication were included in this study . The study was divided into four phases : 3‐day run‐in phase , treatment phase 1 , wash‐out period , and treatment phase 2 , each lasting 1 week . At the discretion of the patients , up to four patches ( covering a maximum of 560 cm2 ) were applied onto the maximally painful area for 12 consecutive hours daily , always either by day or at night . Throughout the four phases , ongoing pain , allodynia , quality of neuropathic symptoms , quality of sleep , and adverse events were assessed . When , after the wash‐out period , the pain intensity scores did not return to the pre‐treatment values ( ±20 % ) , these patients were excluded from the study . The present study revealed that , as an add‐on therapy , the lidocaine patch 5 % was clearly effective in reducing ongoing pain ( P=0.017 ) and allodynia ( P=0.023 ) during the first 8 h after application and that the patches also worked well over a period of 7 days ( P=0.018 ) in diverse focal PNPS . Calculation of the numbers needed to treat ( NNT ) to obtain one patient with more than 50 % relief of ongoing pain revealed that the NNT of 4.4 in the present study compared reasonably well with other studies of PHN , such as topically applied capsaicin ( NNT : 5.3–∞ ) or systemic treatment with gabapentin ( NNT : 3.2–5.0 ) Background Several controlled clinical trials have demonstrated the efficacy and safety of the lidocaine patch 5 % ( LP ) for the treatment of postherpetic neuralgia ( PHN ) . Objective To assess the effects of the LP on distinct neuropathic pain qualities common to all neuropathic pain conditions , the authors analyzed data from one of the vehicle-controlled trials in which the Neuropathic Pain Scale ( NPS ) , the only assessment tool specifically design ed to measure the distinct components of neuropathic pain , was administered . Methods and Results To improve the sensitivity of the NPS to treatment effects , only patients who , at the time of enrollment in the study , reported moderate-to-severe pain on the NPS ( as defined by a score ≥4/10 reported for at least 6 of the 10 individual NPS items ) were included in the analysis . Thus , 96 patients were included in this analysis . After a 3-week , vehicle-controlled study , LP improved all assessed pain qualities to a greater extent than the placebo patch , as measured by the NPS 10 , a sum score including all 10 NPS item scores ( p = 0.043 ) , and an NPS 8 score , which included scores for all 8 pain descriptors , excluding “ unpleasantness ” and “ global intensity ” ( p = 0.042 ) . Separate analysis of all 8 items believed not to reflect allodynia ( NPS NA ; excluding “ skin sensitivity ” and “ surface pain ” ) also demonstrated superiority ( p = 0.022 ) , as did analysis of the subitems that are believed not to be primarily related to peripheral pathophysiological events ( the “ NPS 4 ” : “ sharp , ” “ hot , ” “ dull , ” and “ deep ” pains;p = 0.013 ) . Conclusions This study demonstrates that LP reduces the intensity of all common neuropathic pain qualities and thus may be of potential benefit for nonallodynic neuropathic pain states . Furthermore , these findings suggest that peripheral mechanisms may play a role in the pathophysiological development of pain qualities that heretofore have been assumed not to involve peripheral mechanisms , such as “ dull , ” “ deep , ” “ sharp , ” and “ burning ” pains Objective : To explore the feasibility of prospect ively monitoring treatment efficacy and tolerability of infliximab , etanercept , and leflunomide over a two year period in patients with established rheumatoid arthritis ( RA ) in clinical practice using a structured protocol . Methods : All patients with RA at seven centres in southern Sweden , for whom at least two disease modifying antirheumatic drugs , including methotrexate , had failed or not been tolerated , who started treatment with either infliximab , etanercept , or leflunomide were included . They were evaluated at predefined times using a st and ardised protocol including items required for evaluating response to the American College of Rheumatology ( ACR ) or EULAR criteria . All adverse events were recorded using World Health Organisation terminology . Concomitant treatment and survival while receiving a drug were recorded . Results : During the study 166 patients were treated with etanercept , 135 with infliximab , and 103 with leflunomide . Treatment response as determined by the ACR and EULAR response criteria was similar for the tumour necrosis factor ( TNF ) blockers . The TNF blockers performed significantly better than leflunomide both as determined by the response criteria and by survival on drug analysis . Thus 79 % and 75 % continued to receive etanercept or infliximab compared with 22 % of patients who started leflunomide after 20 months . The spectrum of side effects did not differ from those previously reported in the clinical trials . The initial two year experience of a protocol for postmarketing surveillance of etanercept , infliximab , and leflunomide shows that a structured protocol with central data h and ling can be used in clinical practice for documenting the performance of newly introduced drugs . Conclusions : Efficacy data for the TNF blockers comply with results in clinical trials , whereas leflunomide appeared to perform worse than in clinical trials . Prolonged monitoring is required to identify possible rare side effects This study compared the efficacy of topical lidocaine patches versus vehicle ( placebo ) patches applied directly to the painful skin of subjects with postherpetic neuralgia ( PHN ) utilizing an ' enriched enrollment ' study design . All subjects had been successfully treated with topical lidocaine patches on a regular basis for at least 1 month prior to study enrollment . Subjects were enrolled in a r and omized , two-treatment period , vehicle-controlled , cross-over study . The primary efficacy variable was ' time to exit ' ; subjects were allowed to exit either treatment period if their pain relief score decreased by 2 or more categories on a 6-item Pain Relief Scale for any 2 consecutive days . The median time to exit with the lidocaine patch phase was greater than 14 days , whereas the vehicle patch exit time was 3.8 days ( P < 0.001 ) . At study completion , 25/32 ( 78.1 % ) of subjects preferred the lidocaine patch treatment phase as compared with 3/32 ( 9.4 % ) the placebo patch phase ( P < 0.001 ) . No statistical difference was noted between the active and placebo treatments with regards to side effects . Thus , topical lidocaine patch provides significantly more pain relief for PHN than does a vehicle patch . Topical lidocaine patch is a novel therapy for PHN that is effective , does not cause systemic side effects , and is simple to use Abstract Objectives Topical lidocaine is effective in postherpetic neuralgia ( PHN ) . The aim of the present investigation was to classify patients according to their predominant peripheral nociceptor function and to compare these data with the results of a controlled study using dermal lidocaine patch . Methods Within the skin area of maximal pain QST ( thermotest ) and QCART ( histamine iontophoresis and laser Doppler flowmetry ) were performed prospect ively in 18 PHN patients . A controlled study using cutaneous lidocaine ( lidocaine 5 % patch , IBSA ) followed . Results Six patients ( group I , sensitised nociceptors ) had no sensory loss . Heat pain thresholds were equal or lower than on the contralateral side . Histamine – induced flare and axon reflex vasodilatation were not different on both sides . Histamine evoked pain increased . In 12 patients ( group II , nociceptor impairment ) heat pain thresholds were higher than contralateral . Histamine – induced flare was impaired or abolished . Histamine did not induce any sensation . Lidocaine was efficacious in the entire group of patients . Subgroup analysis revealed that patients with impairment of nociceptor function had significantly greater pain reduction under lidocaine vs placebo . Patients with preserved and sensitised nociceptors demonstrated no significant pain relief . Conclusions PHN patients differ concerning their cutaneous nociceptor function : In the group I pain is caused by pathologically sensitised nociceptors . In subset II there is a loss of function of cutaneous C – nociceptors within the allodynic skin . Patients responded well to topical lidocaine even if the skin was completely deprived of nociceptors . Different underlying mechanims of lidocaine action in nociceptor – deprived skin are discussed ABSTRACT Facial pain has a considerable impact on quality of life . Accurate incidence estimates in the general population are scant . The aim was therefore to estimate the incidence rate ( IR ) of trigeminal neuralgia ( TGN ) , postherpetic neuralgia ( PHN ) , cluster headache ( CH ) , occipital neuralgia ( ON ) , local neuralgia ( LoN ) , atypical facial pain ( AFP ) , glossopharyngeal neuralgia ( GPN ) and paroxysmal hemicrania ( PH ) in the Netherl and s. In the population ‐based Integrated Primary Care Information ( IPCI ) medical record data base potential facial pain cases were identified from codes and narratives . Two medical doctors review ed medical records , question naires from general practitioners and specialist letters using criteria of the International Association for the Study of Pain . A pain specialist arbitrated if necessary and a r and om sample of all cases was evaluated by a neurologist . The date of onset was defined as date of first specific symptoms . The IR was calculated per 100,000 PY . Three hundred and sixty‐two incident cases were ascertained . The overall IR [ 95 % confidence interval ] was 38.7 [ 34.9–42.9 ] . It was more common among women compared to men . Trigeminal neuralgia and cluster headache were the most common forms among the studied diseases . Paroxysmal hemicrania and glossopharyngeal neuralgia were among the rarer syndromes . The IR increased with age for all diseases except CH and ON , peaking in the 4th and 7th decade , respectively . Postherpetic neuralgia , CH and LoN were more common in men than women . From this we can conclude that facial pain is relatively rare , although more common than estimated previously based on hospital data OBJECTIVE Topical lidocaine patch is effective in the treatment of post-herpetic neuralgia ( PHN ) , but not suited for paroxysmal pain because of the long latency of analgesia . Here , we examined the efficacy of 8 % lidocaine pump spray ( Xylocaine pump spray , XPS ) for PHN . DESIGN Twenty-four patients with PHN were recruited into a r and omized , double-blind , placebo-controlled , crossover study ( study 1 ) , and 100 patients with PHN were recruited into an open-labeled study ( study 2 ) . In study 1 , patients were r and omized to receive either XPS or saline placebo pump spray ( PPS ) applied to the painful skin areas . Following a 7-day period , patients were crossed over to receive the alternative treatment . In study 2 , XPS was prescribed for patients who were advised to use the spray anytime , with a 2-hour gap between applications , for 2 weeks . The pain was assessed with a visual analogue scale ( VAS ) . Details of use were noted in the diary . RESULTS In study 1 , greater decreases in VAS of persistent pain followed application of XPS ( baseline : 6.1 + /- 1.7 cm , 15-minute post-spray : 2.3 + /- 2.5 cm , mean + /- SD ) than with PPS ( 6.1 + /- 1.7 cm , 5.7 + /- 1.6 cm , [ P < 0.01 ] ) . The effect persisted for a median of 4.5 hours ( range , 2 to 24 hours ) after application . In study 2 , 13 of 100 patients discontinued the treatment because of mild local side effects or insufficient effect . In the remaining 87 patients , XPS maintained significant pain relief relative to baseline throughout the 2-week period . Satisfaction with the therapy was reported by 79 % of patients . CONCLUSIONS In both studies , XPS provided a significant improvement in PHN due to its prompt analgesia , lack of systemic side effects , and convenience of use Topical application of lidocaine is an effective approach for treatment of post-herpetic neuralgia and other painful neuropathies . Lidocaine inhibits voltage-gated Na(+ ) channels and it most likely reduces excitability of cutaneous sensory neurons which can be hyperexcitable or spontaneously active in states of neuropathic pain . However , lidocaine and other local anesthetics also exert a pronounced neurotoxicity and they activate the irritant receptors TRPV1 and TRPA1 . In this r and omized and double-blinded study , we explored the ability of lidocaine patches ( 5 % ) to alter sensory function and epidermal nerve fiber density in skin of healthy volunteers . As assessed by quantitative sensory testing , significantly elevated thresholds for touch , pin prick pain and mechanically induced wind-up were observed in skin treated with lidocaine patches . These effects reversed to baseline values within 2days after termination of the treatment . Pressure pain and thresholds for heat and cold-induced pain were not affected by the lidocaine patch . A moderate but significant decrease in epidermal nerve fiber density was observed in skin blister roofs obtained after 42days of treatment with lidocaine patches . The placebo patch did not induce any changes in sensory thresholds or nerve fiber density . In conclusion , lidocaine patches seem to have differential effects on sensory modalities in healthy skin . A degeneration of epidermal nerve fibers has previously been demonstrated for patches containing the TRPV1-agonist capsaicin and our findings suggest that this effect might also be relevant for lidocaine patches . These data warrant further studies on molecular mechanisms mediating a relief of neuropathic pain by topical lidocaine A double-blind comparative clinical trial was performed with topical aspirin versus lidocaine for the treatment of 40 patients with postherpetic neuralgia . The percentage improvement following topical aspirin application was 72.2 + /- 19.9 S.D. , while with lidocaine it was 72.8 + /- 25.3 S.D. These results suggest that the effect of topical treatment with aspirin is as good as that with lidocaine , since there was no significant difference ( P = 0.778 ) between the two drugs in respect of pain reduction and accordingly the topical application of acetylsalicylic acid can be equally recommended Abstract Objective : Prospect i ve evaluation of the long-term efficacy and safety of the 5 % lidocaine medicated plaster in patients with post-herpetic neuralgia ( PHN ) . Research design and methods : Patients with persisting pain for ≥3 months after acute herpes zoster and a baseline pain intensity of at least 4 on an 11-point numerical rating scale ( NRS 0–10 ) were treated with 5 % lidocaine medicated plasters for up to 5 years and monitored in regular intervals . Efficacy parameters are presented for the first 4 years and include patients ’ recall of pain relief ( 6-point verbal rating scale ( VRS ) , clinical global impression of change ( CGIC ) , patients ’ global impression of change PGIC ) , and the global evaluations of study medication . Safety parameters ( clinical examination , skin evaluation , laboratory ) and adverse events ( AEs ) were assessed at regular visits . Clinical trial registration : KF10004/02 . Results : A total of 102 patients continuing from a 1 year main study period were included in an extension phase of up to 3 years . Ten patients ( 9.8 % ) dropped out due to lack of efficacy and 9 patients ( 8.8 % ) due to treatment-related AEs ; 56 patients ( 54.9 % ) left the study for non-treatment-related reasons . Twenty-seven patients ( 26.4 % ) were still under treatment after a total treatment period of 4 years . On average , a pain relief of at least 4.3 ( between moderate and a lot ) was achieved throughout the study . At all visits the CGIC and the PGIC were much or very much improved in about 80 % of patients . At the final visit , study medication was rated at least to be good by 91 % of physicians and 89 % of patients . Drug-related adverse events ( DRAEs ) were reported in 19 of 102 patients , mainly mild to moderate localized skin reactions . There were no hints for a reduced analgesic effect or an increase of DRAEs with long-term treatment . Conclusions : This study demonstrates that long-term treatment of ≥12 months with the 5 % lidocaine medicated plaster is effective and well tolerated in PHN patients . These findings support the recommendations to use the 5 % lidocaine medicated plaster as baseline therapy for localized neuropathic pain after herpes zoster infection ( PHN ) Abstract Background and objective : Post-herpetic neuralgia ( PHN ) is a distressing neuropathic pain condition mainly affecting elderly patients . Neuropathic pain symptoms can be of a burning , shooting and stabbing nature , and may continue for prolonged periods and are often poorly controlled by polymedication . The aim of this study was to evaluate the analgesic efficacy and safety of topical analgesic treatment ( 5 % lidocaine [ lignocaine ] medicated plaster ) compared with placebo plaster in patients with PHN . Methods : This was a double-blind , placebo plaster-controlled , parallel-group , multicentre study employing enriched enrolment with r and omized withdrawal methodology . After an initial 8-week open-label , active run-in phase , responders entered a 2-week r and omized , double-blind , placebo-controlled phase . The study was conducted at 33 outpatient investigational centres in 12 European countries . Patients with PHN were selected who were aged ≥50 years , had experienced neuropathic pain persisting for ≥3 months after rash healing , and had a mean pain intensity of ≥4 on an 11-point numerical rating scale . A total of 265 patients entered the open-label phase and subsequently a pre-defined number of 71 patients entered the r and omized phase . Patients applied up to three 5 % lidocaine medicated plasters for up to 12 hours per day . The primary endpoint of the study was time-to-exit due to a ≥2-point reduction in pain relief on two consecutive days of plaster application using a 6-point verbal rating scale . Results : Of the 265 patients entering the run-in phase , 51.7 % achieved at least moderate pain relief . In the double-blind phase ( full analysis set , n = 71 ) , median times-to-exit were 13.5 ( range 2–14 ) and 9.0 ( range 1–14 ) days for lidocaine and placebo plaster groups , respectively ( p = 0.151 ) . For per- protocol patients ( n = 34 ) , median time-to-exit was 14.0 ( range 3–14 ) and 6.0 ( range 1–14 ) days for lidocaine and placebo plaster groups , respectively ( p = 0.0398 ) . Drug-related adverse events occurred in 13.6 % of patients . Treatment with 5 % lidocaine medicated plaster was associated with improvements in pain , allodynia , quality of life and sleep measures . Conclusions : This study adds to a growing body of evidence that the 5 % lidocaine medicated plaster can be considered a valuable treatment option for patients with PHN , providing beneficial effects on pain , allodynia , quality of life and sleep , with minimal adverse effects |
13,858 | 29,352,373 | Evidence suggests that sleep extension had the most beneficial effects on subsequent performance .
Consistent with previous research , these results suggest that sleep plays an important role in some , but not all , aspects of athletes ’ performance and recovery . | Background Athletes experience various situations and conditions that can interfere with their sleep , which is crucial for optimal psychological and physiological recovery as well as subsequent performance .
Conventional sleep screening and intervention approaches may not be efficacious for athletes given their lifestyle , the dem and s of training and travel associated with interstate/international competition .
Objectives The present systematic review aim ed to summarize and evaluate sleep intervention studies targeting subsequent performance and recovery in competitive athletes .
Based on the findings , a secondary aim was to outline a possible sleep intervention for athletes , including recommendations for content , mode of delivery and evaluation . | We describe the development of a cognitive therapy intervention for chronic insomnia . The therapy is based on a cognitive model which suggests that the processes that maintain insomnia include : ( 1 ) worry and rumination , ( 2 ) attentional bias and monitoring for sleep-related threat , ( 3 ) unhelpful beliefs about sleep , ( 4 ) misperception of sleep and daytime deficits and ( 5 ) the use of safety behaviors that maintain unhelpful beliefs . The aim of cognitive therapy for insomnia is to reverse all five maintaining processes during both the night and the day . In an open trial 19 patients meeting diagnostic criteria for primary insomnia were treated with cognitive therapy for insomnia . Assessment s were completed pretreatment , posttreatment and at 3- , 6- and 12-month followup . The significant improvement in both nighttime and daytime impairment evident at the posttreatment assessment was retained up to the 12 month followup The aim of this study was to identify indicators of non-functional overreaching ( NFOR ) in team sport athletes undertaking intensive training loads . Eighteen semi-professional rugby league players were r and omly assigned into two pair matched groups . One group completed 6 weeks of normal training ( NT ) whilst the other group was deliberately overreached through intensified training ( IT ) . Both groups then completed the same 7-day stepwise training load reduction taper . Multistage fitness test ( MSFT ) performance , $ $ \ifmmode\exp and after\dot\else\exp and after\.\fi{V}{\text{O}}_{{2\max } } $ $ , peak aerobic running velocity ( Vmax ) , maximal heart rate , vertical jump , 10-s cycle sprint performance and body mass were measured pre- and post-training period and following the taper . Hormonal , haematological and immunological parameters were also measured pre-training and following weeks 2 , 4 and 6 of training and post-taper . MANOVA for repeated measures with contrast analysis indicated that MSFT performance and $ $ \ifmmode\exp and after\dot\else\exp and after\.\fi{V}{\text{O}}_{{2\max } } $ $ were significantly reduced in the IT group over time and condition , indicating that a state of overreaching was attained . However , the only biochemical measure that was significantly different between the IT and NT group was the glutamine to glutamate ( Gln/Glu ) ratio even though testosterone , testosterone to cortisol ( T/C ) ratio , plasma glutamate , and CK activity were significantly changed after training in both groups . Positive endurance and power performance changes were observed post-taper in the IT group confirming NFOR . These changes were associated with increases in the T/C ratio and the Gln/Glu ratio and decreases in plasma glutamate and CK activity . These results indicate that although there was no single reliable biochemical marker of NFOR in these athletes , the Gln/Glu ratio and MSFT test may be useful measures for monitoring responses to IT in team sport athletes BACKGROUND Chronic insomnia is a common health problem with substantial consequences in older adults . Cognitive behavioral treatments are efficacious but not widely available . The aim of this study was to test the efficacy of brief behavioral treatment for insomnia ( BBTI ) vs an information control ( IC ) condition . METHODS A total of 79 older adults ( mean age , 71.7 years ; 54 women [ 70 % ] ) with chronic insomnia and common comorbidities were recruited from the community and 1 primary care clinic . Participants were r and omly assigned to either BBTI , consisting of individualized behavioral instructions delivered in 2 intervention sessions and 2 telephone calls , or IC , consisting of printed educational material . Both interventions were delivered by a nurse clinician . The primary outcome was categorically defined treatment response at 4 weeks , based on sleep question naires and diaries . Secondary outcomes included self-report symptom and health measures , sleep diaries , actigraphy , and polysomnography . RESULTS Categorically defined response ( 67 % [ n = 26 ] vs 25 % [ n = 10 ] ; χ(2 ) = 13.8 ) ( P < .001 ) and the proportion of participants without insomnia ( 55 % [ n = 21 ] vs 13 % [ n = 5 ] ; χ(2 ) = 15.5 ) ( P < .001 ) were significantly higher for BBTI than for IC . The number needed to treat was 2.4 for each outcome . No differential effects were found for subgroups according to hypnotic or antidepressant use , sleep apnea , or recruitment source . The BBTI produced significantly better outcomes in self-reported sleep and health ( group × time interaction , F(5,73 ) = 5.99 , P < .001 ) , sleep diary ( F(8,70 ) = 4.32 , P < .001 ) , and actigraphy ( F(4,74 ) = 17.72 , P < .001 ) , but not polysomnography . Improvements were maintained at 6 months . CONCLUSION We found that BBTI is a simple , efficacious , and durable intervention for chronic insomnia in older adults that has potential for dissemination across medical setting s. TRIAL REGISTRATION clinical trials.gov Identifier : NCT00177203 We determined the effect of coingestion of caffeine ( Caff ) with carbohydrate ( CHO ) on rates of muscle glycogen re synthesis during recovery from exhaustive exercise in seven trained subjects who completed two experimental trials in a r and omized , double-blind crossover design . The evening before an experiment subjects performed intermittent exhaustive cycling and then consumed a low-CHO meal . The next morning subjects rode until volitional fatigue . On completion of this ride subjects consumed either CHO [ 4 g/kg body mass ( BM ) ] or the same amount of CHO + Caff ( 8 mg/kg BM ) during 4 h of passive recovery . Muscle biopsies and blood sample s were taken at regular intervals throughout recovery . Muscle glycogen levels were similar at exhaustion [ approximately 75 mmol/kg dry wt ( dw ) ] and increased by a similar amount ( approximately 80 % ) after 1 h of recovery ( 133 + /- 37.8 vs. 149 + /- 48 mmol/kg dw for CHO and Caff , respectively ) . After 4 h of recovery Caff result ed in higher glycogen accumulation ( 313 + /- 69 vs. 234 + /- 50 mmol/kg dw , P < 0.001 ) . Accordingly , the overall rate of re synthesis for the 4-h recovery period was 66 % higher in Caff compared with CHO ( 57.7 + /- 18.5 vs. 38.0 + /- 7.7 mmol x kg dw(-1 ) x h(-1 ) , P < 0.05 ) . After 1 h of recovery plasma Caff levels had increased to 31 + /- 11 microM ( P < 0.001 ) and at the end of the recovery reached 77 + /- 11 microM ( P < 0.001 ) with Caff . Phosphorylation of CaMK(Thr286 ) was similar after exercise and after 1 h of recovery , but after 4 h CaMK(Thr286 ) phosphorylation was higher in Caff than CHO ( P < 0.05 ) . Phosphorylation of AMP-activated protein kinase (AMPK)(Thr172 ) and Akt(Ser473 ) was similar for both treatments at all time points . We provide the first evidence that in trained subjects coingestion of large amounts of Caff ( 8 mg/kg BM ) with CHO has an additive effect on rates of postexercise muscle glycogen accumulation compared with consumption of CHO alone INTRODUCTION Elite athletes frequently undergo periods of intensified training ( IT ) within their normal training program . These periods can lead athletes into functional overreaching , characterized by high perceived fatigue , impaired sleep , and performance . Because whole-body cryostimulation ( WBC ) has been proven to be an effective recovery method in the short term ( < 76 h ) , we investigated whether daily WBC sessions during IT could prevent exercise and sleep-related signs of overreaching . METHODS After a normal training week ( BASE ) , 10 elite synchronized swimmers performed two 2-wk IT periods in a r and omized crossover fashion using WBC daily ( ITWBC ) or not ( ITCON ) , separated by 9 d of light training . Swim time trials ( 400 m ) were performed at BASE and after each IT to quantify blood lactate ( [La]B ) , HR ( HR400 ) , salivary alpha amylase ( [α-amylase]s400 ) , and cortisol ( [cortisol]s400 ) responses . Swimmers wore a wrist actigraph nightly to monitor sleep patterns . RESULTS Swim speed ( 400 m ) , [La]B400 , and [α-amylase]s400 decreased from BASE to ITCON , although no significant changes were found after ITWBC . Decreased swim speed was correlated to decreased HR400 and [cortisol]s400 . During ITCON , significant decreases in actual sleep duration ( -21 ± 7 min ) and sleep efficiency ( -1.9 % ± 0.8 % ) were observed , with increased sleep latency ( + 11 ± 5 min ) and fatigue compared with BASE , although these variables did not change during ITWBC . Using a qualitative statistical analysis , we observed that daily WBC use result ed in a 98 % , 59 % , 66 % , and 78 % chance of preserving these respective variables compared with ITCON . CONCLUSION WBC use during IT helped mitigate the signs of functional overreaching observed during ITCON , such as reduced sleep quantity , increased fatigue , and impaired exercise capacity . These results support the daily use of WBC by athletes seeking to avoid functional overreaching during key periods of competition preparation Abstract Objectives : To improve well-being and performance indicators in a group of Australian Football League ( AFL ) players via a six-week sleep optimisation programme . Design : Prospect i ve intervention study following observations suggestive of reduced sleep and excessive daytime sleepiness in an AFL group . Methods : Athletes from the Adelaide Football Club were invited to participate if they had played AFL senior-level football for 1–5 years , or if they had excessive daytime sleepiness ( Epworth Sleepiness Scale [ ESS ] > 10 ) , measured via ESS . An initial education session explained normal sleep needs , and how to achieve increased sleep duration and quality . Participants ( n = 25 ) received ongoing feedback on their sleep , and a mid-programme education and feedback session . Sleep duration , quality and related outcomes were measured during week one and at the conclusion of the six-week intervention period using sleep diaries , actigraphy , ESS , Pittsburgh Sleep Quality Index , Profile of Mood States , Training Distress Scale , Perceived Stress Scale and the Psychomotor Vigilance Task . Results : Sleep diaries demonstrated an increase in total sleep time of approximately 20 min ( 498.8 ± 53.8 to 518.7 ± 34.3 ; p < .05 ) and a 2 % increase in sleep efficiency ( p < 0.05 ) . There was a corresponding increase in vigour ( p < 0.001 ) and decrease in fatigue ( p < 0.05 ) . Conclusions : Improvements in measures of sleep efficiency , fatigue and vigour indicate that a sleep optimisation programme may improve athletes ’ well-being . More research is required into the effects of sleep optimisation on athletic performance ABSTRACT The concept of recovery strategies includes various ways to achieve a state of well-being , prevent underrecovery syndromes from occurring and re-establish pre-performance states . A systematic application of individualised relaxation techniques is one of those . Following a counterbalanced cross-over design , 27 sport science students ( age 25.22 ± 1.08 years ; sports participation 8.08 ± 3.92 h/week ) were r and omly assigned to series of progressive muscle relaxation , systematic breathing , power nap , yoga , and a control condition . Once a week , over the course of five weeks , their repeated sprint ability was tested . Tests ( 6 sprints of 4 s each with 20 s breaks between them ) were executed on a non-motorised treadmill twice during that day intermitted by 25 min breaks . RM-ANOVA revealed significant interaction effects between the relaxation conditions and the two sprint sessions with regard to average maximum speed over all six sprints , F(4,96 ) = 4.06 , P = 0.004 , = 0.15 . Post-hoc tests indicated that after systematic breathing interventions , F(1,24 ) = 5.02 , P = 0.033 , = 0.18 , participants performed significantly better compared to control sessions . As the focus of this study lied on basic mechanisms of relaxation techniques in sports , this r and omised controlled trial provides us with distinct knowledge on their effects , i.e. , systematic breathing led to better performances , and therefore , seems to be a suited relaxation method during high-intensity training ABSTRACT Elite soccer players are at risk of reduced recovery following periods of sleep disruption , particularly following late-night matches . It remains unknown whether improving sleep quality or quantity in such scenarios can improve post-match recovery . Therefore , the aim of this study was to investigate the effect of an acute sleep hygiene strategy ( SHS ) on physical and perceptual recovery of players following a late-night soccer match . In a r and omised cross-over design , two highly-trained amateur teams ( 20 players ) played two late-night ( 20:45 ) friendly matches against each other seven days apart . Players completed an SHS after the match or proceeded with their normal post-game routine ( NSHS ) . Over the ensuing 48 h , objective sleep parameters ( sleep duration , onset latency , efficiency , wake episodes ) , countermovement jump ( CMJ ; height , force production ) , YoYo Intermittent Recovery test ( YYIR2 ; distance , maximum heart rate , lactate ) , venous blood ( creatine kinase , urea and c-reactive protein ) and perceived recovery and stress markers were collected . Sleep duration was significantly greater in SHS compared to NSHS on match night ( P = 0.002 , d = 1.50 ) , with NSHS significantly less than baseline ( P < 0.001 , d = 1.95 ) . Significant greater wake episodes occurred on match night for SHS ( P = 0.04 , d = 1.01 ) , without significant differences between- or within-conditions for sleep onset latency ( P = 0.12 ) , efficiency ( P = 0.39 ) or wake episode duration ( P = 0.07 ) . No significant differences were observed between conditions for any physical performance or venous blood marker ( all P > 0.05 ) ; although maximum heart rate during the YYIR2 was significantly higher in NSHS than SHS at 36 h post-match ( P = 0.01 ; d = 0.81 ) . There were no significant differences between conditions for perceptual “ overall recovery ” ( P = 0.47 ) or “ overall stress ” ( P = 0.17 ) . Overall , an acute SHS improved sleep quantity following a late-night soccer match ; albeit without any improvement in physical performance , perceptual recovery or blood-borne markers of muscle damage and inflammation Background / aim The purpose of this study was to develop a subjective , self-report , sleep-screening question naire for elite athletes . This paper describes the development of the Athlete Sleep Screening Question naire ( ASSQ ) . Methods A convenience sample of 60 elite athletes was r and omly distributed into two groups ; 30 athletes completed a survey composed of current psychometric tools , and 30 athletes completed a revised survey and a sleep specialist structured clinical interview . An item analysis was performed on the revised survey with comparison to clinical decisions regarding appropriate intervention based on a sleep specialist assessment . Results A comparison of existing sleep-screening tools with determination of clinical need from a sleep specialist showed low consistency , indicating that current sleep-screening tools are unsuitable for assessing athlete sleep . A new 15-item tool was developed ( ASSQ ) by selecting items from existing tools that more closely associated with the sleep specialist 's review s. Based on test-retest percentage agreement and the κ-statistic , we found good internal consistency and reliability of the ASSQ . To date , 349 athletes have been screened , and 46 ( 13.2 % ) identified as requiring follow-up consultation with a sleep specialist . Results from the follow-up consultations demonstrated that those athletes identified by the ASSQ as abnormal sleepers have required intervention . Conclusions The research developed a new athlete-specific sleep-screening question naire . Our findings suggest that existing sleep-screening tools are unsuitable for assessing sleep in elite athletes . The ASSQ appears to be more accurate in assessing athlete sleep ( based on comparison with expert clinical assessment ) . The ASSQ can be deployed online and provides clinical cut-off scores associated with specific clinical interventions to guide management of athletes ’ sleep disturbance . The next phase of the research is to conduct a series of studies comparing results from the ASSQ to blinded clinical review s and to data from objective sleep monitoring to further establish the validity of the ASSQ as a reliable sleep screening tool for elite athletes OBJECTIVES The current study aim ed to evaluate school-based motivational sleep education programs ( SEPs ) with adjunct bright light therapy ( BLT ) and /or parental involvement ( PI ) . DESIGN R and omized controlled trial . SETTING Six high schools , matched on socio-economic status ( SES ) . PARTICIPANTS A total of 193 adolescents ( mean age , 16.3 ± 0.4 years , 79%f ) . INTERVENTION Classes were r and omly assigned to ( i ) SEP + BLT , ( ii ) SEP + PI , ( iii ) SEP + BLT + PI , or ( iv ) classes-as-usual ( CAU ) . Sleep education programs involved 4 × 50 minute classes ( over 4 weeks ) based on a Motivational Interviewing framework ( Sleep Med 2011;12:246 - 251 ) . Students in BLT groups attempted a weekend phase advance using portable green light LED glasses ( 500 nm ; 506 lux ) . Parents of PI groups watched a series of 4 YouTube clips ( 2 - 3 minutes in length ) outlining their adolescent 's learning in class and how they could assist . Students in the CAU groups continued their regular classes . MEASUREMENTS Online question naires measuring sleep knowledge , sleep patterns ( bedtime , sleep latency , total sleep time [ TST ] , etc ) and mood at preintervention and postintervention and 6-week follow-up . Intervention groups also completed a motivation-to-change question naire and provided qualitative feedback . RESULTS Improvements in sleep knowledge ( d = 0.59 - 0.88 ) , sleep onset latency ( d = 0.45 - 0.50 ) , TST ( d = 0.32 - 0.57 ) , and mood ( d = 0.24 - 0.46 ) were observed in all intervention groups relative to the CAU group . Similar improvements were observed in a subgroup of students identified as having delayed sleep timing ( ie , sleep knowledge : d = 0.45 - 0.92 ; sleep onset latency : d = 0.59 - 0.82 ; TST : d = 0.82 - 1.18 ) . Increases in motivation to regularize out of bedtimes , obtain morning bright light ( BLT groups ) , and avoid sleeping-in on weekends occurred ( all P < .005 ) . CONCLUSIONS This motivational SEP produced meaningful and similar benefits for adolescents in all intervention groups . Longer BLT ( ie , over school holidays ) and more intensive parental inclusion should be investigated in future studies PURPOSE The aim of this study was to determine the effects of 30 h of sleep deprivation on consecutive-day intermittent-sprint performance and muscle glycogen content . METHODS Ten male , team-sport athletes performed a single-day " baseline " session and two consecutive-day experimental trials separated either by a normal night 's sleep ( CONT1 and CONT2 ) or no sleep ( SDEP1 and SDEP2 ) . Each session included a 30-min grade d exercise run and 50-min intermittent-sprint exercise protocol , including a 15-m maximal sprint every minute and self-paced exercise bouts of varying intensities . Muscle biopsies were extracted before and after exercise during the baseline session and before exercise on day 2 during experimental trials . Voluntary force and activation of the right quadriceps , nude mass , HR , core temperature , capillary blood lactate and glucose , RPE , and a modified POMS were recorded before , after , and during the exercise protocol s. RESULTS Mean sprint times were slower on SDEP2 ( 2.78±0.17 s ) compared with SDEP1 ( 2.70±0.16 s ) and CONT2 ( 2.74±0.15 s , P<0.05 ) . Distance covered during self-paced exercise was reduced during SDEP2 during the initial 10 min compared with SDEP1 and during the final 10 min compared with CONT2 ( P<0.05 ) . Muscle glycogen concentration was lower before exercise on SDEP2 ( 209±60 mmol·kg dry weight ) compared with CONT2 ( 274±54 mmol·kg dry weight , P=0.05 ) . Voluntary force and activation were reduced on day 2 of both conditions ; however , both were lower in SDEP2 compared with CONT2 ( P<0.05 ) . Sleep loss did not affect RPE but negatively affected POMS ratings ( P<0.05 ) . CONCLUSIONS Sleep loss and associated reductions in muscle glycogen and perceptual stress reduced sprint performance and slowed pacing strategies during intermittent-sprint exercise for male team-sport athletes |
13,859 | 29,183,774 | This review demonstrated that rush and cluster schedules are clinical ly and immunological efficacious , with faster effect than conventional schedules .
No relevant difference with respect to clinical outcomes was noticed between subgroups ( pediatric , adult and mixed population s ) .
Regarding safety , most local adverse reactions were mild and there were neither life-threatening systemic reactions nor fatal events .
No relevant differences in the incidence and severity of either local or systemic reactions between the accelerated schedule group and control group were registered .
Accelerated SCIT build-up schedules are effective in the treatment of respiratory allergy in pediatric patients , representing a safe alternative to the conventional schedules with the advantage of achieving clinical effectiveness sooner | BACKGROUND Accelerated subcutaneous immunotherapy ( SCIT ) schedules represent an alternative to conventional SCIT , providing immunotherapy benefits in a shorter period of time .
The objectives of this systematic review were to assess clinical and immunological efficacy as well as safety of accelerated SCIT build-up schedules for the treatment of respiratory allergy in pediatric patients . | Cluster immunotherapy represents an interesting alternative to conventional up‐dosing schedules because it allows achieving the maintenance dose within a shorter time interval . In this study , the efficacy and safety of cluster immunotherapy with a high polymerized allergen extract of a grass/rye pollen mixture have been evaluated in a r and omized , double‐blind , placebo‐controlled , multicenter study Although many patients with allergic rhinoconjunctivitis have symptoms due to sensitization with more than one pollen allergen , and mixed pollen extracts are widely used for allergen immunotherapy in practice , there are few published trials Background and Objectives : Allergy to house dust mite is one of the most common causes of allergic rhinitis ( AR ) in China . We sought to compare the efficacy and safety of a 6-week cluster schedule of specific immunotherapy with that of a 14-week conventional schedule for the treatment of subjects with persistent AR . Methods : The trial was a prospect i ve and r and omized study involving 96 patients with persistent AR , aged 14–60 years , who were allergic to Dermatophagoides pteronyssinus . While 48 patients were r and omly assigned to the cluster schedule reaching the maintenance dose within 6 weeks , the other 48 were r and omly assigned to the conventional schedule reaching the maintenance dose within 14 weeks . Eighty-nine patients completed a 1-year treatment course . While kinetic changes in clinical efficacy and adverse reactions were observed during the treatment , quality of life , cutaneous reactivity and serum-specific immunoglobulin E to Dermatophagoides pteronyssinus were measured before and after treatment . Results : The cluster schedule reduced the time to reach the maintenance dose by 57 % and caused mild systemic adverse reactions after 1.0 % of injections ( 6.7 % of patients ) , with no differences in comparison with the conventional schedule . Cluster specific immunotherapy led to decreases in clinical symptoms and earlier use of medication than did the conventional schedule . Similar improvements in quality of life and reduced cutaneous reactivity without significant changes in specific immunoglobulin E were observed in both groups after 1 year . Conclusions : The cluster schedule is a safe alternative to the conventional schedule with the advantage of achieving clinical effectiveness sooner BACKGROUND Few studies have investigated the use of specific immunotherapy ( SIT ) for childhood seasonal allergic asthma . OBJECTIVE We sought to examine the efficacy and safety of SIT with Alutard SQ grass pollen ( Phleum pratense Alutard SQ ; ALK-Abelló , Hørsholm , Denmark ) in children with seasonal allergic asthma . METHODS A r and omized , double-blind , placebo-controlled study assessing the efficacy of grass pollen SIT over 2 pollen seasons was performed . Children ( 3 - 16 years ) with a history of seasonal allergic asthma sensitized to grass pollen ( P pratense ) and requiring at least 200 microg of inhaled beclomethasone equivalent per day were enrolled . Subjects with symptomatic asthma or rhinoconjunctivitis outside the grass pollen season were excluded . The primary outcome measure was a combined asthma symptom-medication score during the second pollen season . Secondary outcome measures included end-point titration skin prick testing and conjunctival and bronchial provocation testing to allergen , sputum eosinophilia , exhaled nitric oxide , and adverse events . RESULTS Thirty-nine subjects were enrolled . Thirty-five subjects provided data for analysis . The use of SIT was associated with a substantial reduction in asthma symptom-medication score compared with that after placebo ( P = .04 ) . There were also significant reductions in cutaneous ( P = .002 ) , conjunctival ( P = .02 ) , and bronchial ( P = .01 ) reactivity to allergen after SIT compared with that after placebo . The 2 groups had similar levels of airway inflammation , despite a trend toward less inhaled steroid use in the active group . No serious adverse events were reported , and no subjects withdrew because of adverse events . CONCLUSION The study has shown that SIT is effective and well tolerated in children with seasonal allergic asthma to grass pollen BACKGROUND The clinical efficacy of allergen immunotherapy using therapeutic vaccines containing modified allergen extracts has been previously shown . OBJECTIVE To evaluate the clinical efficacy of a vaccine containing depigmented , polymerized extract of Dermatophagoides pteronyssinus in asthmatic children , monosensitized to mites , after 4 months of treatment . MATERIAL AND METHODS A total of 30 mite-allergic , asthmatic children ( age range , 8 - 16 years ) were entered in the study ; 15 were treated with the modified allergen extract ( active group ) and 15 received only pharmacologic treatment ( control group ) . The study was open , controlled and parallel with r and om allocation of the patients to each of the groups . Efficacy was evaluated using allergen-specific bronchial challenge tests , dose-response skin-prick tests , and symptom and medication scores . The results of the bronchial challenges and dose-response skin-prick tests were compared at baseline and after 4 months of treatment . The build up phase consisted of 4 injections in 2 days , followed by 4 injections of the maintenance dose . RESULTS All patients of the active group concluded the study , whereas 2 of the control group did not . In the active group , there was a significant difference in the PC20FEV1 ( P < .01 ) after 4 months . The mean allergen quantity needed was 26 microg at baseline vs. 309 microg after 4 months ( a 12.8-fold increase ) . There was no difference in the control group ( 5 tg at baseline vs 8 microg at the end ) . A significant reduction in the number of cases with dual bronchial response was observed in the treated group ( P < .05 ) . Two treated patients of this group experienced a negative bronchial challenge after 4 months of treatment . The group of active patients also experienced significant improvement in skin reactivity and symptom and medication scores . CONCLUSIONS Vaccines containing depigmented polymerized extracts of D pteronyssinus are safe and effective in the treatment of mite allergic asthmatic children , and provide clinical benefit after 4 months of treatment To cite this article : Pfaar O , Urry Z , Robinson DS , Sager A , Richards D , Hawrylowicz CM , Bräutigam M , Klimek L. A r and omized placebo‐controlled trial of rush preseasonal depigmented polymerized grass pollen immunotherapy . Allergy 2012 ; 67 : 272–279 BACKGROUND The inhalation of Salsola kali pollen is a common cause of respiratory diseases in Europe and North America . OBJECTIVE To evaluate the efficacy and safety of a depigmented and glutaraldehyde-polymerized therapeutic vaccine of S kali . METHODS The trial was r and omized , double-blind , and placebo-controlled using a rush protocol in the build-up phase . Sixty patients with rhinoconjunctivitis ( 19 also had mild asthma ) were r and omly allocated to receive either active treatment ( polymerized extract ) or placebo . The final distribution was 41 patients in the active and 19 in the placebo group . Side effects were registered . Symptom and medication scores and the number of days free of symptoms during the pollen season were assessed to evaluate the clinical efficacy . A Rhinoconjunctivitis Quality of Life Question naire was completed in the previous pollen season ( before treatment ) and during the pollen season 1 year later ( in the trial ) . Dose-response skin tests were performed at baseline and at the end of the trial . RESULTS There was a significant difference ( P < .05 ) in symptom and medication scores between both groups during the pollen season , with the active group the one that had fewer symptoms and lower intake of medication . The number of days without symptoms was higher in the active group ( P < .05 ) . This group also had a significant improvement in the Rhinoconjunctivitis Quality of Life Question naire and a reduction in skin sensitivity . No moderate or severe systemic reactions were registered . CONCLUSION Immunotherapy with this modified vaccine of S kali pollen is safe and efficacious to treat patients clinical ly sensitive to this pollen . CLINICAL IMPLICATION S Patients allergic to S kali ( Russian thistle ) can be successfully treated with immunotherapy to improve symptoms of allergic rhinitis and asthma , reduce medication use , and improve quality of life parameters We investigated the effects of cluster specific immunotherapy ( SIT ) with Dermatophagoides pteronyssinus ( Der p ) on CD4(+ ) CD25(+ ) Foxp3(+ ) Treg cells and IL-10-secreting type I T regulatory ( Tr1 ) cells in Der p-sensitized children with allergic rhinitis ( AR ) . We performed a prospect i ve r and omized study involving 46 children ( aged 8 - 13 yr ) , of whom 25 children received Der p-SIT + pharmacotherapy and 21 received only pharmacotherapy , over a period of 1 yr . Prior to and at end of treatment , CD4(+ ) CD25(+ ) Foxp3(+ ) Treg cells and allergen-specific IL-10(+ ) IL-4(- ) , IFN-γ(+ ) IL-4(- ) , and IL-4(+ ) IFN-γ-CD4(+ ) T cells were measured by flow cytometry . Similarly , IL-4 , IFN-γ , and IL-10 in supernatants from allergen-stimulated peripheral blood mononuclear cell ( P BMC ) cultures were measured by ELISA , and the suppressive effect of CD4(+ ) CD25(high ) T cells on cell proliferation and cytokine release was estimated from both groups . Allergen-specific serum IgE and IgG4 were also assessed at the beginning and end of treatment by RAST and ELISA , respectively . The levels of allergen-specific Tr1 cells , IgG4 , and allergen-induced IL-10 synthesis from P BMC cultures were significantly increased after SIT for 1 yr compared with baseline levels ( p < 0.001 for all ) , with significant correlation between increased levels of Tr1 cells and improvements in nasal symptoms ( r = 0.48 , p < 0.05 ) . In contrast , the levels of CD4(+ ) CD25(+ ) Foxp3(+ ) T cells , allergen-specific Th1 and Th2 cells , the production of IL-4 and IFN-γ , and the function of CD4(+ ) CD25(high ) T cells were not altered in either group at the end of treatment . These data suggest that the up-regulation of Tr1 cells may play an important role in SIT and be a useful marker of successful SIT in AR patients |
13,860 | 27,500,670 | The preponderance of data for oral contraceptive pills , injectable norethisterone enanthate , and levonorgestrel implants do not suggest an association with HIV acquisition , though data for implants are limited .
Although confounding in these observational data can not be excluded , new information increases concerns about DMPA and HIV acquisition risk in women . | OBJECTIVE AND DESIGN Some studies suggest that specific hormonal contraceptive methods [ particularly depot medroxyprogesterone acetate ( DMPA ) ] may increase women 's HIV acquisition risk .
We up date d a systematic review to incorporate recent epidemiological data . | Objectives : To evaluate the effect of hormonal contraception including combined oral contraceptives ( COCs ) , and the injectable progestins depo-medroxyprogesterone acetate ( DMPA ) and norethisterone enanthate ( Net-En ) on the risk of HIV acquisition among women in South Africa . Design / methods : We analyzed data from 5567 women aged 16–49 years participating in the Carraguard Phase 3 Efficacy Trial . Participants were interviewed about contraceptive use and sexual behaviors and underwent pelvic examinations and HIV testing quarterly . We used marginal structural Cox regression models to estimate the effect of hormonal contraception exposure on HIV acquisition risk among women overall and among young women ( 16–24 years ) in particular . Results : Two hundred and seventy participants became HIV-infected ( 3.7 per 100 woman-years ) ; HIV incidence was 2.8 , 4.6 , 3.5 and 3.4 per 100 woman-years in the COC , DMPA , Net-En and nonhormonal contraceptive groups , respectively ( P = 0.09 ) . The adjusted hazard ratios ( AHRs ) were 0.84 [ 95 % confidence interval ( CI ) 0.51–1.39 ] , 1.28 ( 95 % CI 0.92–1.78 ) and 0.92 ( 95 % CI 0.64–1.32 ) among COC , DMPA and Net-En users , respectively , compared with the nonhormonal group controlling for covariates . Age modified the effect of hormonal contraception on HIV acquisition risk ; among young women , the AHRs were 1.02 ( 95 % CI 0.46–2.28 ) for COCs , 1.68 ( 95 % CI 0.96–2.94 ) for DMPA and 1.36 ( 95 % CI0.78–2.35 ) for Net-En users . Conclusions : In this study conducted among South African women , hormonal contraception did not significantly increase the risk of HIV acquisition . However , the effect estimate does not rule out a moderate increase in HIV risk associated with DMPA use found in some other recent studies With two million new HIV infections annually , ongoing investigations of risk factors for HIV acquisition is critical to guide ongoing HIV prevention efforts . We conducted a prospect i ve cohort analysis of HIV uninfected female sex workers enrolled at an HIV prevention clinic in Nairobi ( n = 1640 ) . In the initially HIV uninfected cohort ( 70 % ) , we observed 34 HIV infections during 1514 person-years of follow-up , i.e. an annual incidence of 2.2 % ( 95 % CI 1.6–3.1 % ) . In multivariable Cox Proportional Hazard analysis , HIV acquisition was associated with a shorter baseline duration of sex work ( aHR 0.76 , 95 % CI 0.63–0.91 ) , minimum charge/sex act ( aHR 2.74 , 0.82–9.15 , for low vs. intermediate ; aHR 5.70 , 1.96–16.59 , for high vs. intermediate ) , N. gonorrhoeae infection ( aAHR 5.89 , 95 % CI 2.03–17.08 ) , sex with casual clients during menses ( aHR 6.19 , 95 % CI 2.58–14.84 ) , Depo Provera use ( aHR 5.12 , 95 % CI 1.98–13.22 ) , and estimated number of annual unprotected regular partner contacts ( aHR 1.004 , 95 % CI 1.001–1.006 ) . Risk profiling based on baseline predictors suggested that substantial heterogeneity in HIV risk is evident , even within a key population . These data highlight several risk factors for HIV acquisition that could help to re-focus HIV prevention messages BACKGROUND Hormonal contraceptives are used widely but their effects on HIV-1 risk are unclear . We aim ed to assess the association between hormonal contraceptive use and risk of HIV-1 acquisition by women and HIV-1 transmission from HIV-1-infected women to their male partners . METHODS In this prospect i ve study , we followed up 3790 heterosexual HIV-1-serodiscordant couples participating in two longitudinal studies of HIV-1 incidence in seven African countries . Among injectable and oral hormonal contraceptive users and non-users , we compared rates of HIV-1 acquisition by women and HIV-1 transmission from women to men . The primary outcome measure was HIV-1 seroconversion . We used Cox proportional hazards regression and marginal structural modelling to assess the effect of contraceptive use on HIV-1 risk . FINDINGS Among 1314 couples in which the HIV-1-seronegative partner was female ( median follow-up 18·0 [ IQR 12·6 - 24·2 ] months ) , rates of HIV-1 acquisition were 6·61 per 100 person-years in women who used hormonal contraception and 3·78 per 100 person-years in those who did not ( adjusted hazard ratio 1·98 , 95 % CI 1·06 - 3·68 , p=0·03 ) . Among 2476 couples in which the HIV-1-seronegative partner was male ( median follow-up 18·7 [ IQR 12·8 - 24·2 ] months ) , rates of HIV-1 transmission from women to men were 2·61 per 100 person-years in couples in which women used hormonal contraception and 1·51 per 100 person-years in couples in which women did not use hormonal contraception ( adjusted hazard ratio 1·97 , 95 % CI 1·12 - 3·45 , p=0·02 ) . Marginal structural model analyses generated much the same results to the Cox proportional hazards regression . INTERPRETATION Women should be counselled about potentially increased risk of HIV-1 acquisition and transmission with hormonal contraception , especially injectable methods , and about the importance of dual protection with condoms to decrease HIV-1 risk . Non-hormonal or low-dose hormonal contraceptive methods should be considered for women with or at-risk for HIV-1 . FUNDING US National Institutes of Health and the Bill & Melinda Gates Foundation Vaginal Gel Versus HIV HIV prevention technologies for women are urgently needed , especially in sub-Saharan Africa where young women bear the greatest burden of the HIV epidemic . Abdool Karim et al. ( p. 1168 ; published online 19 July ) present the results of the CAPRISA 004 r and omized control trial . The nearly 3-year-long trial , conducted in urban and rural South African women , tested the efficacy of a vaginal gel containing the antiretroviral drug tenofovir in preventing HIV infection . The dosing strategy required application of the gel both before and after coitus , and with this regime HIV infection was reduced by approximately 39 % overall , by 54 % in women with high adherence to the protocol , and with no increase in overall adverse event rates . Tenofovir in a vaginal gel formulation shows significant protection against HIV infection in a r and omized control trial . The Centre for the AIDS Program of Research in South Africa ( CAPRISA ) 004 trial assessed the effectiveness and safety of a 1 % vaginal gel formulation of tenofovir , a nucleotide reverse transcriptase inhibitor , for the prevention of HIV acquisition in women . A double-blind , r and omized controlled trial was conducted comparing tenofovir gel ( n = 445 women ) with placebo gel ( n = 444 women ) in sexually active , HIV-uninfected 18- to 40-year-old women in urban and rural KwaZulu-Natal , South Africa . HIV serostatus , safety , sexual behavior , and gel and condom use were assessed at monthly follow-up visits for 30 months . HIV incidence in the tenofovir gel arm was 5.6 per 100 women-years ( person time of study observation ) ( 38 out of 680.6 women-years ) compared with 9.1 per 100 women-years ( 60 out of 660.7 women-years ) in the placebo gel arm ( incidence rate ratio = 0.61 ; P = 0.017 ) . In high adherers ( gel adherence > 80 % ) , HIV incidence was 54 % lower ( P = 0.025 ) in the tenofovir gel arm . In intermediate adherers ( gel adherence 50 to 80 % ) and low adherers ( gel adherence < 50 % ) , the HIV incidence reduction was 38 and 28 % , respectively . Tenofovir gel reduced HIV acquisition by an estimated 39 % overall , and by 54 % in women with high gel adherence . No increase in the overall adverse event rates was observed . There were no changes in viral load and no tenofovir resistance in HIV seroconverters . Tenofovir gel could potentially fill an important HIV prevention gap , especially for women unable to successfully negotiate mutual monogamy or condom use BACKGROUND Preexposure prophylaxis with antiretroviral drugs has been effective in the prevention of human immunodeficiency virus ( HIV ) infection in some trials but not in others . METHODS In this r and omized , double-blind , placebo-controlled trial , we assigned 2120 HIV-negative women in Kenya , South Africa , and Tanzania to receive either a combination of tenofovir disoproxil fumarate and emtricitabine ( TDF-FTC ) or placebo once daily . The primary objective was to assess the effectiveness of TDF-FTC in preventing HIV acquisition and to evaluate safety . RESULTS HIV infections occurred in 33 women in the TDF-FTC group ( incidence rate , 4.7 per 100 person-years ) and in 35 in the placebo group ( incidence rate , 5.0 per 100 person-years ) , for an estimated hazard ratio in the TDF-FTC group of 0.94 ( 95 % confidence interval , 0.59 to 1.52 ; P=0.81 ) . The proportions of women with nausea , vomiting , or elevated alanine aminotransferase levels were significantly higher in the TDF-FTC group ( P=0.04 , P<0.001 , and P=0.03 , respectively ) . Rates of drug discontinuation because of hepatic or renal abnormalities were higher in the TDF-FTC group ( 4.7 % ) than in the placebo group ( 3.0 % , P=0.051 ) . Less than 40 % of the HIV-uninfected women in the TDF-FTC group had evidence of recent pill use at visits that were matched to the HIV-infection window for women with seroconversion . The study was stopped early , on April 18 , 2011 , because of lack of efficacy . CONCLUSIONS Prophylaxis with TDF-FTC did not significantly reduce the rate of HIV infection and was associated with increased rates of side effects , as compared with placebo . Despite substantial counseling efforts , drug adherence appeared to be low . ( Supported by the U.S. Agency for International Development and others ; FEM-PrEP Clinical Trials.gov number , NCT00625404 . ) The use of hormonal contraception has been associated with an increased risk of HIV-1 in some studies but not in others . We analysed data from a 10-year prospect i ve cohort study of female sex workers in Mombasa , Kenya . In multivariate analysis , women using the injectable contraceptive depot medroxyprogesterone acetate and women using oral contraceptive pills were at increased risk of HIV-1 acquisition compared with women using no contraceptive method Objective : To evaluate the effect of oral and injectable hormonal contraception on the risk of HIV acquisition among women in South Africa and Zimbabwe . Design : Secondary data analysis of 4913 sexually active women aged 18–49 years followed for up to 24 months in the Methods for Improving Reproductive Health in Africa ( MIRA ) phase III effectiveness trial of the diaphragm and lubricant gel for HIV prevention . Methods : Participants were interviewed quarterly about contraception and sexual behavior and were tested for pregnancy , HIV , and other sexually transmitted infections . We used a Cox proportional hazards marginal structural model , weighted by the inverse probability of hormonal contraception use , to compare the risk of HIV acquisition among nonpregnant women reporting use of combined oral contraceptive pills ( COC ) , progestin-only pills ( POP ) , and /or injectable hormonal contraception to women not using these methods . Results : During the study , 283 participants seroconverted . Use of oral contraceptives ( POP or COC ) was not associated with HIV risk [ adjusted hazard ratio ( HRa ) = 0.86 , 95 % confidence interval ( CI ) 0.32 , 1.78 ] . Injectable hormonal contraception was associated with a small nonsignificant risk of HIV infection ( HRa = 1.34 , 95 % CI 0.75 , 2.37 ) . The effect of injectable hormonal contraception was similar in the unweighted site-adjusted only ( HRa = 1.32 , 95 % CI 1.00 , 1.74 ) and baseline factor adjusted models ( HRa = 1.27 , 95 % CI 0.94 , 1.72 ) . Conclusions : In this study , oral contraceptives were not associated with HIV acquisition . There is substantial uncertainty in the effect of injectable hormonal contraception on HIV risk . These findings underscore the importance of dual protection with condoms and the need for diverse contraceptive options for women at risk of HIV infection The aim of this study was to determine HIV-1 incidence among women of reproductive age in Malawi . A prospect i ve study design was followed . HIV-1 uninfected women were followed up for nine visits during a period of 12 months . At baseline , women received HIV-1 counselling and testing . At each visit , venous blood was collected for HIV-1 testing . Incidence rate for HIV-1 was estimated using person-years of follow up ( PYFU ) . Risk factors for HIV acquisition were assessed using Cox proportional hazard models . A total of 842 HIV-1 negative women were enrolled in the study . Of these , 787 had subsequent HIV testing and 31 were found HIV-1 infected ; an overall incidence rate of 4.51 ( 95 % confidence interval : 2.96–6.06 ) per 100 PYFU was obtained . Young age , using hormonal injectable contraceptives and bacterial vaginosis were the main predictors of HIV acquisition . The incidence of HIV continues to be high among women in Malawi , and young women appear to be at higher risk Objectives To prepare for future HIV prevention trials , we conducted prospect i ve cohort studies among women working in food and recreational facilities in northern Tanzania . We examined the prevalence and incidence of HIV and HSV-2 , and associated risk factors . Methods Women aged 18–44 years working in food and recreational facilities were screened to determine their eligibility for the studies . Between 2008–2010 , HIV-negative women were enrolled and followed for 12 months . At enrolment and 3-monthly , we collected socio-demographic and behavioural data , and performed clinical examinations for collection of biological specimens that were tested for reproductive tract infections . Risk factors for HIV and HSV-2 incidence were investigated using Poisson regression models . Results We screened 2,229 and enrolled 1,378 women . The median age was 27 years ( interquartile range , IQR 22 , 33 ) , and median duration working at current facility was 2 years . The prevalences of HIV at screening and HSV-2 at enrolment were 16 % and 67 % , respectively . Attendance at the 12-month visit was 86 % . HIV and HSV-2 incidence rates were 3.7 ( 95 % confidence interval , CI : 2.8,5.1 ) and 28.6 ( 95 % CI : 23.5,35.0)/100 person-years , respectively . Women who were separated , divorced , or widowed were at increased risk of HIV ( adjusted incidence rate ratio , aRR = 6.63 ; 95 % CI : 1.97,22.2 ) and HSV-2 ( aRR = 2.00 ; 95 % CI : 1.15,3.47 ) compared with married women . Women reporting ≥3 partners in the past 3 months were at higher HIV risk compared with women with 0–1 partner ( aRR = 4.75 ; 95 % CI : 2.10,10.8 ) , while those who had reached secondary education or above were at lower risk of HSV-2 compared with women with incomplete primary education ( aRR = 0.42 ; 95 % CI : 0.22,0.82 ) . Conclusions HIV and HSV-2 rates remain substantially higher in this cohort than in the general population , indicating urgent need for effective interventions . These studies demonstrate the feasibility of conducting trials to test new interventions in this highly-mobile population Objectives : A r and omized , double-blind , placebo-controlled trial ( RCT ) of herpes simplex virus type 2 suppressive therapy with acyclovir 400 mg twice daily conducted among women in northwestern Tanzania reported a similar rate of HIV acquisition in both trial arms ( Current Controlled Trials number IS RCT N35385041 ) . Risk factors for HIV incidence were examined in the context of 3-monthly follow-up visits offering both voluntary counselling and testing and care for sexually transmitted infections . Design : Prospect i ve cohort analysis of trial participants enrolled and followed for up to 30 months . Methods : Risk factors for HIV acquisition were analysed using Cox regression . Results : Overall , 821 herpes simplex virus type 2 seropositive , HIV seronegative women were r and omized ; 400 r and omized to acyclovir and 421 to placebo ; 659 ( 80.3 % ) completed follow-up . HIV incidence was 4.27 per 100 person-years . There was no overall impact of acyclovir on HIV incidence [ hazard ratio = 1.01 ; 95 % confidence interval ( CI ) 0.61–1.66 ] . HIV acquisition was independently associated with younger age at enrolment ( age 16–19 vs. 30–35 : hazard ratio = 4.02 ; 95 % CI 1.67–9.68 ) , alcohol consumption at enrolment ( ≥30 drinks/week vs. none : hazard ratio = 4.39 , 95 % CI 1.70–11.33 ) , having paid sex within the previous 3 months ( hazard ratio = 1.82 , 95 % CI 1.09–3.05 ) , recent infection with gonorrhoea ( hazard ratio = 3.62 , 95 % CI 1.62–8.08 ) and injections in the previous 3 months ( hazard ratio = 3.45 , 95 % CI 1.62–7.34 ) . There was some evidence of an association between HIV incidence and living in the recruitment community for less than 2 years ( hazard ratio = 1.75 , 95 % CI 0.98–3.10 ) and exposure to hormonal contraception ( hazard ratio = 1.60 , 95 % CI 0.93–2.76 ) . Conclusion : A high incidence of HIV was observed in this trial cohort , especially in young women . Interventions are needed to address the risk associated with alcohol use and to sustain control of other sexually transmitted infections Background HIV is prevalent in Sofala Province , Mozambique . To inform future prevention research , we undertook a study in the provincial capital ( Beira ) to measure HIV incidence in women at higher risk of HIV and assess the feasibility of recruiting and retaining them as research participants . Methods Women age 18–35 were recruited from schools and places where women typically meet potential sexual partners . Eligibility criteria included HIV-seronegative status and self-report of at least 2 sexual partners in the last month . History of injection drug use was an exclusion criterion , but pregnancy was not . Participants were scheduled for monthly follow-up for 12 months , when they underwent face-to-face interviews , HIV counseling and testing , and pregnancy testing . Results 387 women were eligible and contributed follow-up data . Most were from 18–24 years old ( median 21 ) . Around one-third of participants ( 33.8 % ) reported at least one new sexual partner in the last month . Most women ( 65.5 % ) reported not using a modern method of contraception at baseline . Twenty-two women seroconverted for a prospect i ve HIV incidence of 6.5 per 100 woman-years ( WY ; 95 % confidence interval ( CI ) : 4.1–9.9 ) . Factors associated with HIV seroconversion in the multivariable analysis were : number of vaginal sex acts without using condoms with partners besides primary partner in the last 7 days ( hazard ratio ( HR ) 1.7 ; 95 % CI : 1.2–2.5 ) and using a form of contraception at baseline other than hormonal or condoms ( vs. no method ; HR 25.3 ; 95 % CI : 2.5–253.5 ) . The overall retention rate was 80.0 % for the entire follow-up period . Conclusions We found a high HIV incidence in a cohort of young women reporting risky sexual behavior in Beira , Mozambique . HIV prevention programs should be strengthened . Regular HIV testing and condom use should be encouraged , particularly among younger women with multiple sexual partners Background Reliable HIV incidence estimates for Mozambique are limited . We conducted a prospect i ve HIV incidence study as part of a clinical research site development initiative in Chókwè district , Gaza Province , southern Mozambique . Methods Between June 2010 and October 2012 , we recruited women at sites where women at higher risk of HIV infection would likely be found . We enrolled and tested 1,429 sexually active women in the screening phase and 479 uninfected women in the prospect i ve phase . Participants were scheduled for 12 + months follow-up , when they underwent face-to-face interviews , HIV counseling and testing , and pregnancy testing . We observed a total of 373.1 woman-years ( WY ) of follow-up , with mean ( median ) of 9.4 ( 9.7 ) women-months per participant . Results The prevalence of HIV was 29.4 % ( 95 % confidence interval [ CI ] : 27.0–31.8 % ) . In multivariable logistic regression analysis , factors that remained significantly associated with prevalent HIV were : older age ( OR : 0.6 ; 95 % CI : 0.4–0.7 ) , lower educational level ( OR : 0.4 ; 95 % CI : 0.3–0.7 ) , and using hormonal contraception ( OR : 0.6 ; 95 % CI : 0.4–0.7 ) or condoms ( OR : 0.5 ; 95 % CI : 0.3–0.7 ) . We observed an HIV incidence rate of 4.6 per 100 WY ( 95 % CI : 2.7 , 7.3 ) . The HIV incidence was 4.8 per 100 WY ( 95 % CI : 2.5 , 8.3 ) in women aged 18–24 years , 4.5 per 100 WY ( 95 % CI : 1.2 , 11.4 ) in women aged 25–29 years and 3.2 per 100 WY ( 95 % CI : 0.1 , 18.0 ) in the 30–35 years stratum . None of the demographic factors or time-varying behavioral factors examined was significantly associated with incident HIV infection in bivariable analysis at p≤0.10 . Conclusions We found a high HIV incidence among sexually active young women in Chókwè , Mozambique . HIV prevention programs should be strengthened in the area , with more comprehensive reproductive health services , regular HIV testing , condom promotion , and messaging about multiple sexual partners BACKGROUND Several observational studies have reported that HIV-1 acquisition seems to be higher in women who use depot medroxyprogesterone acetate ( DMPA ) than in those who do not use hormonal contraception . We aim ed to assess whether two injectable progestin-only contraceptives , DMPA and norethisterone enanthate ( NET-EN ) , confer different risks of HIV-1 acquisition . METHODS We included data from South African women who used injectable contraception while participating in theVOICE study , a multisite , r and omised , placebo-controlled trial that investigated the safety and efficacy of three formulations of tenofovir for prevention of HIV-1 infection in women between Sept 9 , 2009 , and Aug 13 , 2012 . Women were assessed monthly for contraceptive use and incident infection . We estimated the difference in incident HIV-1infection between DMPA and NET-EN users by Cox proportional hazards regression analyses in this prospect i ve cohort . The VOICE trial is registered with Clinical Trials.gov , NCT00705679 . FINDINGS 3141 South African women using injectable contraception were included in the present analysis : 1788 (56·9%)solely used DMPA , 1097 ( 34·9 % ) solely used NET-EN , and 256 ( 8·2 % ) used both injectable types at different times during follow-up . During 2733·7 person-years of follow-up , 207 incident HIV-1 infections occurred ( incidence7·57 per 100 person-years , 95 % CI 6·61–8·68 ) . Risk of HIV-1 acquisition was higher among DMPA users ( incidence 8·62 per 100 person-years , 95 % CI 7·35–10·11 ) than among NET-EN users ( 5·67 per 100 person-years , 4·35–7·38;hazard ratio 1·53 , 95 % CI 1·12–2·08 ; p=0·007 ) . This association persisted when adjusted for potential confoundingvariables ( adjusted hazard ratio [ aHR ] 1·41 , 95 % CI 1·06–1·89 ; p=0·02 ) . Among women seropositive for herpes simplex virus type 2 ( HSV-2 ) at enrolment , the aHR was 2·02 ( 95 % CI 1·26–3·24 ) compared with 1·09 (0·78–1·52)for HSV-2-seronegative women ( pinteraction=0·07 ) . INTERPRETATION Although moderate associations in observational analyses should be interpreted with caution , thesefi ndings suggest that NET-EN might be an alternative injectable drug with a lower HIV risk than DMPA in high HIV-1 incidence setting s where NET-EN is available . FUNDING National Institutes of Health , Mary Meyer Scholars Fund , and the Ruth Freeman Memorial Fund Objectives : To determine the risk factors for HIV seroconversion and assess the association between contraceptive use and HIV infection among women attending three large family planning clinics in Dar es Salaam , Tanzania . Design : Prospect i ve cohort study . Methods : Between 1992 and 1995 , 2471 HIV-negative women were followed prospect ively . Information about sociodemographic characteristics , sexual behavior , contraceptive use and other risk factors was collected at recruitment and up date d at follow-up visits . At the end of the study , specimens were collected for HIV testing and laboratory diagnosis of sexually transmitted diseases . Results : The overall HIV incidence was 3.4 per 100 person-years [ 95 % confidence interval ( CI ) , 2.6–4.1 ] . The risk of HIV seroconversion decreased with increasing age ( P = 0.04 , test for trend ) . Women reporting three or more sex partners during the follow-up period had the highest risk of HIV [ age-adjusted relative risk ( RR ) , 4.89 ; 95 % CI , 2.6–9.17 ] . Having an uncircumcised husb and was associated with a significantly increased risk of HIV ( age-adjusted RR , 3.60 ; 95 % CI , 1.1–11.59 ) . The risk of HIV was also significantly increased among women with gonorrhoea ( age-adjusted RR , 3.51 ; 95 % CI , 1.6–7.71 ) and c and idiasis at baseline ( age-adjusted RR , 1.98 ; 95 % CI , 1.1–3.33 ) and among women reporting alcohol consumption during the follow-up period . After controlling for other risk factors , the risk of HIV infection amongst users of oral contraceptive , intrauterine device and injectable contraceptive was not significantly increased . Similarly , there was no significant trend associated with increasing duration of use of any of these contraceptive methods . Conclusion : These findings confirm that a large number of new HIV infections continue to occur in this population . Reassuringly , no significant association was observed between HIV and use of specific contraceptive methods . Interventions to reduce further spread of HIV are still urgently needed Objective To determine the incidence of HIV-1 infection and associated risk factors among young , seronegative , and sexually active women in a mixed rural and urban population in southern Rw and a. Design A prospect i ve cohort study . Methods Between October 1991 and April 1993 , we completed a 2-year follow-up survey among HIV-1-seronegative women aged ≤30 years at the time of their initial HIV-1 screening during pregnancy . All women aged ≤25 years and a r and omly selected sample of 26–30-year olds were invited to participate from five prenatal clinics in the Butare region . The interview focused on potential risk factors for HIV-1 acquisition during the 2-year interval between blood collection . Results Out of 1524 women selected , 1150 ( 75 % ) participated in the follow-up survey . The 2-year incidence of HIV-1 infection was 2.7 % [ 95 % confidence interval ( CD , 1.8–3.9 ] . Teenage women were at the highest risk ( incidence , 10.5 % ; 95 % Cl , 5.2–19.4 ) , with incidence leveling off with increasing age ( P < 0.001 ) . Women who began sexual activity recently were also at higher risk ; the lowest risk category consisted of women aged 26–30 years with 5 or more years of sexual experience . The more urban the geographic residence of the woman , the more likely she was to have acquired HIV-1 infection ( P < 0.001 ) . In the urban and peri-urban zones , the poorest women were at significantly higher risk of incident HIV-1 infection than women reporting higher household income . In a multivariate analysis , young maternal age , marital status ( being single , divorced or widowed ) , multiple sexual partners , and a history of sexually transmitted diseases remained strongly associated with incident HIV-1 infection . Geographic residence , hormonal contraception , and receipt of injections were no longer significantly associated with incident HIV-1 infection when these other factors were accounted for simultaneously . Conclusion Among young Rw and an women , the early years of sexual activity are particularly dangerous for acquisition of HIV-1 infection . Interventions should focus on young teenagers before they become sexually active BACKGROUND The use of injectable progestin-only contraceptives has been associated with increased risk of HIV acquisition in observational studies , but the biological mechanisms of this risk remain poorly understood . We aim ed to assess the effects of progestins on HIV acquisition risk and the immune environment in the female genital tract . METHODS In this prospect i ve cohort , we enrolled HIV-negative South African women aged 18 - 23 years who were not pregnant and were living in Umlazi , South Africa from the Females Rising through Education , Support , and Health ( FRESH ) study . We tested for HIV-1 twice per week to monitor incident infection . Every 3 months , we collected demographic and behavioural data in addition to blood and cervical sample s. The study objective was to characterise host immune determinants of HIV acquisition risk , including those associated with injectable progestin-only contraceptive use . Hazard ratios ( HRs ) were estimated using Cox proportional hazards methods . FINDINGS Between Nov 19 , 2012 , and May 31 , 2015 , we characterised 432 HIV-uninfected South African women from the FRESH study . In this cohort , 152 women used injectable progestin-only contraceptives , 43 used other forms of contraception , and 222 women used no method of long-term contraception . Women using injectable progestin-only contraceptives were at substantially higher risk of acquiring HIV ( 12·06 per 100 person-years , 95 % CI 6·41 - 20·63 ) than women using no long-term contraception ( 3·71 per 100 person-years , 1·36 - 8·07 ; adjusted hazard ratio [ aHR ] 2·93 , 95 % CI 1·09 - 7·868 , p=0·0326 ) . HIV-negative injectable progestin-only contraceptive users had 3·92 times the frequency of cervical HIV target cells ( CCR5 + CD4 T cells ) compared with women using no long-term contraceptive ( p=0·0241 ) . Women using no long-term contraceptive in the luteal phase of the menstrual cycle also had a 3·25 times higher frequency of cervical target cells compared with those in the follicular phase ( p=0·0488 ) , suggesting that a naturally high progestin state had similar immunological effects to injectable progestin-only contraceptives . INTERPRETATION Injectable progestin-only contraceptive use and high endogenous progesterone are both associated with increased frequency of activated HIV targets cells at the cervix , the site of initial HIV entry in most women , providing a possible biological mechanism underlying increased HIV acquisition in women with high progestin exposure . FUNDING The Bill and Melinda Gates Foundation and the National Institute of Allergy and Infectious Diseases Background : Studies of the effect of hormonal contraceptive use on the risk of HIV-1 acquisition have generated conflicting results . A recent study from Ug and a and Zimbabwe found that women using hormonal contraception were at increased risk for HIV-1 if they were seronegative for herpes simplex virus type 2 ( HSV-2 ) , but not if they were HSV-2 seropositive . Objective : To explore the effect of HSV-2 infection on the relationship between hormonal contraception and HIV-1 in a high-risk population . Hormonal contraception has previously been associated with increased HIV-1 risk in this population . Methods : Data were from a prospect i ve cohort study of 1206 HIV-1 seronegative sex workers from Mombasa , Kenya who were followed monthly . Multivariate Cox proportional hazards analyses were used to adjust for demographic and behavioral measures and incident sexually transmitted diseases . Results : Two hundred and thirty-three women acquired HIV-1 ( 8.7/100 person-years ) . HSV-2 prevalence ( 81 % ) and incidence ( 25.4/100 person-years ) were high . In multivariate analysis , including adjustment for HSV-2 , HIV-1 acquisition was associated with use of oral contraceptive pills [ adjusted hazard ratio ( HR ) , 1.46 ; 95 % confidence interval ( CI ) , 1.00–2.13 ] and depot medroxyprogesterone acetate ( adjusted HR , 1.73 ; 95 % CI , 1.28–2.34 ) . The effect of contraception on HIV-1 susceptibility did not differ significantly between HSV-2 seronegative versus seropositive women . HSV-2 infection was associated with elevated HIV-1 risk ( adjusted HR , 3.58 ; 95 % CI , 1.64–7.82 ) . Conclusions : In this group of high-risk African women , hormonal contraception and HSV-2 infection were both associated with increased risk for HIV-1 acquisition . HIV-1 risk associated with hormonal contraceptive use was not related to HSV-2 serostatus Our objective was to estimate HIV seroconversion rates among commercial sex workers ( CSWs ) between 1990 and 1991 and to identify the behavioral , demographic , and reproductive determinants of these rates . This study has a prospect i ve ( n = 240 with 15 cases ) and a cross-sectional component ( n = 271 with 34 cases ) . In November 1990 , HIV-negative female CSWs from 24 brothels in Khon Kaen city were interviewed and were followed prospect ively for up to 1 year . In March , June , and September 1991 , additional HIV-negative CSWs were enrolled and prospect ively followed . HIV seroconversion rates were calculated , and the Cox regression model was used to estimate the relative risks of HIV seroconversion from demographic , sexual practice , and reproductive factors , adjusted for the effects of the others , among 232 of the 240 without missing data . Seroprevalence rates were also calculated for the 271 participants enrolled between March and December 1991 , and relative risks of HIV seroprevalence were calculated for demographic , sexual practice , and reproductive risk factors among 184 of the 271 without missing data . The average seroprevalence was 12.5 % ( 95 % confidence interval 9.6 - 15.4 % ) . With 1,947 person-months of observation obtained from 240 participants who were uninfected at baseline and seen at least twice during the course of the study , the cumulative incidence of HIV seroconversion between November 1990 and December 1991 was 9.4 % ( 95 % confidence interval 5.4 - 13.4 % ) , and the average incidence rate of HIV seroconversion was 9.2 per 100 person-years ( 95 % confidence interval 4.6 - 13.9 per 100 person-years ) . In the multivariate analysis , later date of enrollment into the study , having < 3 months experience as a CSW , and use of injectable contraceptives were the only risk factors that remained significant , with relative risks of 2.1 ( 95 % confidence interval 1.2 - 3.7 ) for enrollment 3 months later , 3.8 ( 95 % confidence interval 1.0 - 14.4 ) for < 3 months experience as a CSW versus > 3 months experience , and 3.9 ( 95 % confidence interval 1.3 - 11.8 ) [ corrected ] for use of injectable contraceptives . In multivariate analysis of the cross-sectional data with 184 participants , of whom 21 were HIV seropositive , risk of HIV seropositivity increased significantly with current syphilis infection ( odds ratio 5.8 , 95 % confidence interval 1.1 - 31.0 ) . The results of this study will contribute to a better underst and ing of the risk factors of infection with HIV and thus allow for better targeting of group-specific interventions , particularly for CSWs and their clients . Further investigation of a possible association between injectable contraceptive use and HIV infection is needed Objectives : To determine the incidence of HIV-1 infection , temporal trends in incidence , and risk factors for seroconversion in a cohort of female commercial sex workers ( CSW ) in upper northern Thail and , the region of Thail and with the highest rates of HIV-1 infection . Methods : CSW were enrolled from 1991 through 1994 and evaluated prospect ively with interviews , physical examination , testing for sexually transmitted diseases ( STD ) , and serologic testing for HIV-1 infection . Results : The incidence of HIV-1 seroconversion in the first year of follow-up was 20.3 per 100 person-years among 126 brothel-based CSW and 0.7 per 100 person-years among 159 other CSW who worked in other venues such as bars or massage parlors . Incidence remained elevated among brothel-based CSW who were enrolled later in the study compared with those who enrolled earlier . Through 1996 , 30 women seroconverted . In a multivariable proportional hazards model , seroconversion was significantly associated ( P < 0.05 ) with brothel-based sex work ( adjusted risk ratio , 7.3 ) and Chlamydia trachomatis cervical infection ( adjusted risk ratio , 3.3 ) . Conclusion : Despite national HIV control efforts and declining rates of infection among young men in Thail and , brothel-based CSW may continue to be at high risk for HIV-1 infection . Additional efforts are needed to provide alternative economic choices for young women , to ensure universal condom use during commercial sex , and to develop new prevention technologies CONTEXT Sexually transmitted infections ( STIs ) are common in female sex workers ( FSWs ) and may enhance susceptibility to infection with human immunodeficiency virus type 1 ( HIV-1 ) . OBJECTIVE To examine regular antibiotic prophylaxis in FSWs as a strategy for reducing the incidence of bacterial STIs and HIV-1 . DESIGN , SETTING , AND PARTICIPANTS R and omized , double-blind , placebo-controlled trial conducted between 1998 - 2002 among FSWs in an urban slum area of Nairobi , Kenya . Of 890 FSWs screened , 466 who were seronegative for HIV-1 infection were enrolled and r and omly assigned to receive azithromycin ( n = 230 ) or placebo ( n = 236 ) . Groups were well matched at baseline for sexual risk taking and STI rates . INTERVENTION Monthly oral administration of 1 g of azithromycin or identical placebo , as directly observed therapy . All participants were provided with free condoms , risk-reduction counseling , and STI case management . MAIN OUTCOME MEASURES The primary study end point was incidence of HIV-1 infection . Secondary end points were the incidence of STIs due to Neisseria gonorrhoeae , Chlamydia trachomatis , Trichomonas vaginalis , Treponema pallidum , and Haemophilus ducreyi , as well as bacterial vaginosis . Analysis of herpes simplex virus type 2 ( HSV-2 ) infection was performed post hoc . RESULTS Seventy-three percent of participants ( n = 341 ) were followed up for 2 or more years or until they reached an administrative trial end point . Incidence of HIV-1 did not differ between treatment and placebo groups ( 4 % [ 19 cases per 473 person-years of follow-up ] vs 3.2 % [ 16 cases per 495 person-years of follow-up ] rate ratio [ RR ] , 1.2 ; 95 % CI , 0.6 - 2.5 ) . Incident HIV-1 infection was associated with preceding infection with N gonorrhoeae ( rate ratio [ RR ] , 4.9 ; 95 % CI , 1.7 - 14.3 ) or C trachomatis ( RR , 3.0 ; 95 % CI , 1.1 - 8.9 ) . There was a reduced incidence in the treatment group of infection with N gonorrhoeae ( RR , 0.46 ; 95 % CI , 0.31 - 0.68 ) , C trachomatis ( RR , 0.38 ; 95 % CI , 0.26 - 0.57 ) , and T vaginalis ( RR , 0.56 ; 95 % CI , 0.40 - 0.78 ) . The seroprevalence of HSV-2 infection at enrollment was 72.7 % , and HSV-2 infection at baseline was independently associated with HIV-1 acquisition ( RR , 6.3 ; 95 % CI , 1.5 - 27.1 ) . CONCLUSIONS Despite an association between bacterial STIs and acquisition of HIV-1 infection , the addition of monthly azithromycin prophylaxis to established HIV-1 risk reduction strategies substantially reduced the incidence of STIs but did not reduce the incidence of HIV-1 . Prevalent HSV-2 infection may have been an important cofactor in acquisition of HIV-1 To examine associations between method of contraception , sexually transmitted diseases ( STDs ) , and incident human immunodeficiency virus type 1 ( HIV-1 ) infection , a prospect i ve observational cohort study was done among female sex workers attending a municipal STD clinic in Mombasa , Kenya . Demographic and behavioral factors significantly associated with HIV-1 infection included type of workplace , condom use , and parity . In multivariate models , vulvitis , genital ulcer disease , vaginal discharge , and C and ida vaginitis were significantly associated with HIV-1 seroconversion . Women who used depo medroxyprogesterone acetate ( DMPA ) had an increased incidence of HIV-1 infection ( hazard ratio [ HR ] , 2.2 ; 95 % confidence interval [ CI ] , 1.4 - 3.4 ) . In a multivariate model controlling for demographic and exposure variables and biologic covariates , the adjusted HR for HIV-1 infection among DMPA users was 2.0 ( CI , 1.3 - 3.1 ) . There was a trend for an association between use of high-dose oral contraceptive pills and HIV-1 acquisition ( HR , 2.6 ; CI , 0.8 - 8.5 ) BACKGROUND The injectable hormonal contraceptive depo-medroxyprogesterone acetate ( DMPA ) has been associated with increased risk of HIV acquisition , but findings are inconsistent . Whether DMPA increases the risk of other sexually transmitted viral infections is unknown . We assessed the association between DMPA use and incident herpes simplex virus type 2 ( HSV2 ) infection in women . METHODS In this prospect i ve study , we enrolled HIV-negative and HSV2-negative women aged 15 - 49 years whose HIV-negative male partners were concurrently enrolled in a r and omised trial of male circumcision in Rakai , Ug and a. We excluded women if either they or their male partners HIV seroconverted . The primary outcome was HSV2 seroconversion , assessed annually . The male circumcision trial was registered with Clinical Trials.gov , number NCT00425984 . FINDINGS Between Aug 11 , 2003 , and July 6 , 2006 , we enrolled 682 women in this study . We noted HSV2 seroconversions in 70 ( 10 % ) women . Incidence was 13·5 per 100 person-years in women consistently using DMPA ( nine incident infections per 66·5 person-years ) , 4·3 per 100 person-years in pregnant women who were not using hormonal contraception ( 18 incident infections per 423·5 person-years ) , and 6·6 per 100 person-years in women who were neither pregnant nor using hormonal contraception ( 35 incident infections per 529·5 person-years ) . Women consistently using DMPA had an adjusted hazard ratio for HSV2 seroconversion of 2·26 ( 95 % CI 1·09 - 4·69 ; p=0·029 ) compared with women who were neither pregnant nor using hormonal contraception . Of 132 women with HSV2-seropositive partners , seroconversion was 36·4 per 100 person-years in consistent DMPA users ( four incident infections per 11 person-years ) and 10·7 per 100 person-years in women who were neither pregnant nor using hormonal contraception ( 11 incident infections per 103 person-years ; adjusted hazard ratio 6·23 , 95 % CI 1·49 - 26·3 ; p=0·012 ) . INTERPRETATION Consistent DMPA use might increase risk of HSV2 seroconversion ; however , study power was low . These findings should be assessed in larger population s with more frequent follow-up than in this study , and other contraceptive methods should also be assessed . Access to a wide range of highly effective contraceptive methods is needed for women , particularly in sub-Saharan Africa . FUNDING Bill and Melinda Gates Foundation , Doris Duke Charitable Foundation , US National Institutes of Health , and Fogarty International Center Objectives : To investigate the association between hormonal contraceptives and risk of HIV-1 seroconversion and prevalence of other sexually transmitted infections . Design : Prospect i ve cohort . Methods : The study population was 2 236 HIV-negative women who were screened in a biomedical intervention trial in Durban , South Africa . The association between the use of hormonal contraceptives and risk of HIV-1 seroconversion was modeled using Cox proportional hazards regression analysis . Prevalence of Chlamydia trachomatis and Neisseria gonorrhoeae infections were assessed using logistic regression models . Results : Hormonal injectables were the most common method of contraceptives ( 46.47 % ) followed by condom use ( 28.04 % ) . Overall , compared with women who reported using condoms or other methods as their preferred form of contraceptive , those who reported using hormonal contraceptives ( injectables and oral pills ) were less likely to use condoms in their last sexual act . Using hormonal injectables during the study was significantly associated with increased risk for HIV-1 infection [ adjusted hazard ratio 1.72 , 95 % confidence interval ( CI ) 1.19–2.49 , P = 0.005 ] ; hormonal injectables were also significantly associated with higher prevalent of C. trachomatis infections ( adjusted odds ratio 2.46 , 95 % CI 1.52–3.97 , P < 0.001 ) . Conclusion : Hormonal injectables are highly effective and well tolerated family planning methods and have played an important role in reducing unplanned pregnancies and maternal and infant mortality . However , they do not protect against HIV-1 and other sexually transmitted infections . This study reinforces the importance of comprehensive contraceptive counseling to women about the importance of dual protection , such as male condoms and hormonal contraceptives use The hazard ratio ( HR ) is the main , and often the only , effect measure reported in many epidemiologic studies . For dichotomous , non – time-varying exposures , the HR is defined as the hazard in the exposed groups divided by the hazard in the unexposed groups . For all practical purpose s , hazards can be thought of as incidence rates and thus the HR can be roughly interpreted as the incidence rate ratio . The HR is commonly and conveniently estimated via a Cox proportional hazards model , which can include potential confounders as covariates . Unfortunately , the use of the HR for causal inference is not straightforward even in the absence of unmeasured confounding , measurement error , and model misspecification . Endowing a HR with a causal interpretation is risky for 2 key reasons : the HR may change over time , and the HR has a built-in selection bias . Here I review these 2 problems and some proposed solutions . As an example , I will use the findings from a Women ’s Health Initiative r and omized experiment that compared the risk of coronary heart disease of women assigned to combined ( estrogen plus progestin ) hormone therapy with that of women assigned to placebo . By using a r and omized experiment as an example , the discussion can focus on the shortcomings of the HR , setting aside issues of confounding and other serious problems that arise in observational studies . The Women ’s Health Initiative followed over 16,000 women for an average of 5.2 years before the study was halted due to safety concerns . The primary result from the trial was a HR . As stated in the abstract and shown in Table 1 of the article , “ Combined hormone therapy was associated with a hazard ratio of 1.24 . ” In addition , Table 2 provided the HRs during each year of follow-up : 1.81 , 1.34 , 1.27 , 1.25 , 1.45 , and 0.70 for years 1 , 2 , 3 , 4 , 5 , and 6 , respectively . Thus , the HR reported in the abstract and Table 1 can be viewed as some sort of weighted average of the period-specific HRs reported in Table 2 . This bring us to Problem 1 : although the HR may change over time , some studies report only a single HR averaged over the duration of the study ’s follow-up . As a result , the conclusions from the study may critically depend on the duration of the follow-up . For example , the average HR in the WHI would have been 1.8 if the study had been halted after 1 year of follow-up , 1.7 after 2 years , 1.2 after 5 years , and —who knows — perhaps 1.0 after 10 years . The 24 % increase in the rate of coronary heart disease that many research ers and journalists consider as the effect of combined hormone therapy is the result of the arbitrary choice of an average follow-up period of 5.2 years . A trial with a shorter follow-up could have reported an 80 % increase , whereas a longer trial might have found little or no increase at all OBJECTIVE To assess the effect of oral and injectable contraceptive use compared to nonhormonal contraceptive use on HIV acquisition among Southern African women enrolled in a microbicide trial . STUDY DESIGN This is a prospect i ve cohort study using data from women enrolled in HIV Prevention Trials Network protocol 035 . At each quarterly visit , participants were interviewed about self-reported contraceptive use and sexual behaviors and underwent HIV testing . Cox proportional hazards regression was used to assess the effect of injectable and oral hormonal contraceptive use on HIV acquisition . RESULTS The analysis included 2830 participants , of whom 106 became HIV infected ( 4.07 per 100 person-years ) . At baseline , 1546 ( 51 % ) participants reported using injectable contraceptives and 595 ( 21 % ) reported using oral contraceptives . HIV incidence among injectable , oral and nonhormonal contraceptive method users was 4.72 , 2.68 and 3.83 per 100 person-years , respectively . Injectable contraceptive use was associated with a nonstatistically significant increased risk of HIV acquisition [ adjusted hazard ratio (aHR)=1.17 ; 95 % confidence interval ( CI ) 0.70 , 1.96 ] , while oral contraceptive use was associated with a nonstatistically significant decreased risk of HIV acquisition ( aHR=0.76 ; 95 % CI 0.37,1.55 ) . CONCLUSION In this secondary analysis of r and omized trial data , a marginal , but nonstatistically significant , increase in HIV risk among women using injectable hormonal contraceptives was observed . No increased HIV risk was observed among women using oral contraceptives . Our findings support the World Health Organization 's recommendation that women at high risk for acquiring HIV , including those using progestogen-only injectable contraception , should be strongly advised to always use condoms and other HIV prevention measures . IMPLICATION S Among Southern African women participating in an HIV prevention trial , women using injectable hormonal contraceptives had a modest increased risk of HIV acquisition ; however , this association was not statistically significant . Continued research on the relationship between widely used hormonal contraceptive methods and HIV acquisition is essential Objective : The objective of this study was to underst and temporal trends in the contribution of different genital tract infections to HIV incidence over 20 years of follow-up in a cohort of high-risk women . Design : A prospect i ve cohort study . Methods : We performed monthly evaluations for HIV , vaginal yeast , bacterial vaginosis , Trichomonas vaginalis , Neisseria gonorrhoeae , nonspecific cervicitis , herpes simplex virus type two ( HSV-2 ) , genital ulcer disease ( GUD ) and genital warts . We used Cox regression to evaluate the association between sexually transmitted infections ( STIs ) and HIV acquisition over four time periods ( 1993–1997 , 1998–2002 , 2003–2007 , 2008–2012 ) . Models were adjusted for age , workplace , sexual risk behaviour , hormonal contraceptive use and other STIs . The result ing hazard ratios were used to calculate population attributable risk percentage ( PAR% ) . Results : Between 1993 and 2012 , 1964 women contributed 6135 person-years of follow-up . The overall PAR% for each infection was prevalent HSV-2 ( 48.3 % ) , incident HSV-2 ( 4.5 % ) , bacterial vaginosis ( 15.1 % ) , intermediate microbiota ( 7.5 % ) , vaginal yeast ( 6.4 % ) , T. vaginalis ( 1.1 % ) , N. gonorrhoeae ( 0.9 % ) , nonspecific cervicitis ( 0.7 % ) , GUD ( 0.8 % ) and genital warts ( −0.2 % ) . Across the four time periods , the PAR% for prevalent HSV-2 ( 40.4 % , 61.8 % , 58.4 % , 48.3 % ) and bacterial vaginosis ( 17.1 % , 19.5 % , 14.7 % , 17.1 % ) remained relatively high and had no significant trend for change over time . The PAR% for trichomoniasis , gonorrhoea , GUD and genital warts remained less than 3 % across the four periods . Conclusion : Bacterial vaginosis and HSV-2 have consistently been the largest contributors to HIV acquisition risk in the Mombasa Cohort over the past 20 years . Interventions that prevent these conditions would benefit women 's health and could reduce their risk of becoming infected with HIV Background : Combined oral contraceptives ( COC ) and depot-medroxyprogesterone acetate ( DMPA ) are among the most widely used family planning methods ; their effect on HIV acquisition is not known . Objective : To evaluate the effect of COC and DMPA on HIV acquisition and any modifying effects of other sexually transmitted infections . Methods : This multicenter prospect i ve cohort study enroled 6109 HIV-uninfected women , aged 18–35 years , from family planning clinics in Ug and a , Zimbabwe and Thail and . Participants received HIV testing quarterly for 15–24 months . The risk of HIV acquisition with different contraceptive methods was assessed ( excluding Thail and , where there were few HIV cases ) . Results : HIV infection occurred in 213 African participants ( 2.8/100 woman-years ) . Use of neither COC [ hazard ratio ( HR ) , 0.99 ; 95 % confidence interval ( CI ) , 0.69–1.42 ] nor DMPA ( HR , 1.25 ; 95 % CI , 0.89–1.78 ) was associated with risk of HIV acquisition overall , including among participants with cervical or vaginal infections . While absolute risk of HIV acquisition was higher among participants who were seropositive for herpes simplex virus 2 ( HSV-2 ) than in those seronegative at enrolment , among the HSV-2-seronegative participants , both COC ( HR , 2.85 ; 95 % CI , 1.39–5.82 ) and DMPA ( HR , 3.97 ; 95 % CI , 1.98–8.00 ) users had an increased risk of HIV acquisition compared with the non-hormonal group . Conclusions : No association was found between hormonal contraceptive use and HIV acquisition overall . This is reassuring for women needing effective contraception in setting s of high HIV prevalence . However , hormonal contraceptive users who were HSV-2 seronegative had an increased risk of HIV acquisition . Additional research is needed to confirm and explain this finding |
13,861 | 29,318,922 | Moderating effects were also found for cue-focality and whether studies controlled for the arousal level of the cues .
The principal finding is that positively-valenced cues improve prospect i ve memory performance and that timing of the manipulation can moderate emotional effects on prospect i ve memory . | ABSTRACT Remembering to perform a behaviour in the future , prospect i ve memory , is essential to ensuring that people fulfil their intentions .
Prospect i ve memory involves committing to memory a cue to action ( encoding ) , and later recognising and acting upon the cue in the environment ( retrieval ) .
Prospect i ve memory performance is believed to be influenced by the emotionality of the cues , however the literature is fragmented and inconsistent . | Some studies have found that prospect i ve memory ( PM ) cues which are emotionally valenced influence age effects in prospect i ve remembering , but it remains unclear whether this effect reflects the operation of processes implemented at encoding or retrieval . In addition , none of the prior ageing studies of valence on PM function have examined potential costs of engaging in different valence conditions , or re source allocation trade-offs between the PM and the ongoing task . In the present study , younger , young-old and old-old adults completed a PM task in which the valence of the cues varied systematic ally ( positive , negative or neutral ) at encoding , but was kept constant ( neutral ) at retrieval . The results indicated that PM accuracy did not vary as a function of affect at encoding , and that this effect did not interact with age group . There was also no main or interaction effect of valence on PM reaction time in PM cue trials , indicating that valence costs across the three encoding conditions were equivalent . Old-old adults ’ PM accuracy was reduced relative to both young-old and younger adults . Prospect i ve remembering incurred dual-task costs for all three groups . Analyses of reaction time data suggested that for both young-old and old-old , these costs were greater , implying differential re source allocation cost trade-offs . However , when reaction time data were expressed as a proportional change that adjusted for the general slowing of the older adults , costs did not differ as a function of group Event-based prospect i ve memory tasks entail detecting cues or reminders in our environment related to previously established intentions . If they are detected at an opportune time , then the intention can be fulfilled . In Experiments 1a-1c , we gave people 3 different nonfocal intentions ( e.g. , respond to words denoting animals ) and discovered that negatively valenced cues delivered the intention to mind less frequently than positively valenced cues . In Experiment 2 , this effect was extended to valenced and neutral sentential context s with convergent results that cues embedded in negatively valenced sentences evoked remembering the intention less often than in positive context s. In addition , both classes of valence caused the intention to be forgotten more often than a more neutral context . We propose that valence has the ability to usurp attentional re sources that otherwise would have supported successful prospect i ve memory performance Prospect i ve memory ( PM ) describes the ability to execute a previously planned action at the appropriate point in time . Although behavioral studies clearly showed that prospect i ve memory performance is affected by the emotional significance attributed to the intended action , no study so far investigated the brain mechanisms subserving the modulatory effect of emotional salience on PM performance . The general aim of the present study was to explore brain regions involved in prospect i ve memory processes when PM cues are associated with emotional stimuli . In particular , based on the hypothesised critical role of the prefrontal cortex in prospect i ve memory in the presence of emotionally salient stimuli , we expected a stronger involvement of aPFC when the retrieval and execution of the intended action is cued by an aversive stimulus . To this aim BOLD responses of PM trials cued by aversive facial expressions were compared to PM trials cued by neutral facial expressions . Whole brain analysis showed that PM task cued by aversive stimuli is differentially associated with activity in the right lateral prefrontal area ( BA 10 ) and in the left cau date nucleus . Moreover a temporal shift between the response of the cau date nucleus that preceded that of aPFC was observed . These findings suggest that the cau date nucleus might provide an early analysis of the affective properties of the stimuli , whereas the anterior lateral prefrontal cortex ( BA10 ) would be involved in a slower and more deliberative analysis to guide goal -directed behaviour This study examined the cue detection in the non-focal event-based prospect i ve memory ( PM ) of individuals with and without a major depressive disorder using behavioural and eye tracking assessment s. The participants were instructed to search on each trial for a different target stimulus that could be present or absent and to make prospect i ve responses to the cue object . PM tasks included cue only and target plus cue , whereas ongoing tasks included target only and distracter only . The results showed that a ) participants with depression performed more poorly than those without depression in PM ; b ) participants with depression showed more fixations and longer total and average fixation duration s in both ongoing and PM conditions ; c ) participants with depression had lower scores on accuracy in target-plus-cue trials than in cue-only trials and had a higher gaze rate of targets on hits and misses in target-plus-cue trials than did those without depression . The results indicate that the state of depression may impair top-down cognitive control function , which in turn results in particular deficits in the engagement of monitoring for PM cues Rationale Prospect i ve memory involves remembering to do something in the future and has a prospect i ve component ( remembering that something must be done ) and a retrospective component ( remembering what must be done and when it must be done ) . Initial studies reported an impairment in prospect ive-memory performance due to acute alcohol consumption . Retrospective-memory studies demonstrated that alcohol effects vary depending on the emotionality of the information that needs to be learned . Objectives The aim of the present study was to investigate possible differential effects of a mild acute alcohol dose ( 0.4 g/kg ) on the prospect i ve and retrospective components of prospect i ve memory depending on cue valence . MethodS eventy-five participants were allocated to an alcohol or placebo group and performed a prospect ive-memory task in which prospect ive-memory cue valence was manipulated ( negative , neutral , positive ) . The multinomial model of event-based prospect i ve memory ( Smith and Bayen 2004 ) was used to measure alcohol and valence effects on the two prospect ive-memory components separately . Results Overall , no main effect of alcohol or valence on prospect ive-memory performance occurred . However , model-based analyses demonstrated a significantly higher retrospective component for positive compared with negative cues in the placebo group . In the alcohol group , the prospect i ve component was weaker for negative than for neutral cues and the retrospective component was stronger for positive than for neutral cues . Group comparisons showed that the alcohol group had a significantly lower prospect i ve component for negative cues and a lower retrospective component for neutral cues . Conclusion This is the first study to demonstrate selective alcohol effects on prospect ive-memory components depending on prospect ive-memory cue valence Obsessive-compulsive disorder can result in a variety of deficits to cognitive performance , including negative consequences for attention and memory performance . The question addressed in the current study concerned whether this disorder influenced performance in an event-based prospect i ve memory task . The results from a sub clinical population indicated that , relative to non-anxious controls and mildly depressed controls , people with obsessive-compulsive tendencies ( washing compulsions ) incur decrements in remembering to respond to cues related to a neutral intention ( respond to animals ) . This deficit was ameliorated by giving the sub clinical group an intention about a threat-related category ( respond to bodily fluids ) and cueing them with concepts that they had previously rated as particularly disturbing to them . Thus , their normal attentional bias for extended processing of threat-related information overcame their natural deficit in event-based prospect i ve memory This study examined the separate influence and joint influences on event-based prospect i ve memory task performance due to the valence of cues and the valence of context s. We manipulated the valence of cues and context s with pictures from the International Affective Picture System . The participants , undergraduate students , showed higher performance when neutral compared to valenced pictures were used for cueing prospect i ve memory . In addition , neutral pictures were more effective as cues when they occurred in a valenced context than in the context of neutral pictures , but the effectiveness of valenced cues did not vary across context s that differed in valence . The finding of an interaction between cue and context valence indicates that their respective influence on event-based prospect i ve memory task performance can not be understood in isolation from each other . Our findings are not consistent with by the prevailing view which holds that the scope of attention is broadened and narrowed , respectively , by positively and negatively valenced stimuli . Instead , our findings are more supportive of the recent proposal that the scope of attention is determined by the motivational intensity associated with valenced stimuli . Consistent with this proposal , we speculate that the motivational intensity associated with different retrieval cues determines the scope of attention , that context s with different valence values determine participants ’ task engagement , and that prospect i ve memory task performance is determined jointly by attention scope and task engagement Prospect i ve memory involves the formation and execution of intended actions and is essential for autonomous living . In this study ( N=32 ) , the effect of the nature of PM cues ( semantic versus perceptual ) on established event-related potentials ( ERPs ) elicited in PM tasks ( N300 and prospect i ve positivity ) was investigated . PM cues defined by their perceptual features clearly elicited the N300 and prospect i ve positivity whereas PM cues defined by semantic relatedness elicited prospect i ve positivity . This calls into question the view that the N300 is a marker of general processes underlying detection of PM cues , but supports existing research showing that prospect i ve positivity represents general post-retrieval processes that follow detection of PM cues . Continued refinement of ERP paradigms for underst and ing the neural correlates of PM is needed So far , little is known about the neurocognitive mechanisms associated with emotion effects on prospect i ve memory ( PM ) performance . Thus , this study aim ed at disentangling possible mechanisms for the effects of emotional valence of PM cues on the distinct phases composing PM by investigating event-related potentials ( ERPs ) . Participants were engaged in an ongoing N-back task while being required to perform a PM task . The emotional valence of both the ongoing pictures and the PM cues was manipulated ( pleasant , neutral , unpleasant ) . ERPs were recorded during the PM phases , such as encoding , maintenance , and retrieval of the intention . A recognition task including PM cues and ongoing stimuli was also performed at the end of the sessions . ERP results suggest that emotional PM cues not only trigger an automatic , bottom-up , capture of attention , but also boost a greater allocation of top-down processes . These processes seem to be recruited to hold attention toward the emotional stimuli and to retrieve the intention from memory , likely because of the motivational significance of the emotional stimuli . Moreover , pleasant PM cues seemed to modulate especially the prospect i ve component , as revealed by changes in the amplitude of the ERP correlates of strategic monitoring as a function of the relevance of the valence for the PM task . Unpleasant pictures seemed to modulate especially the retrospective component , as revealed by the largest old/new effect being elicited by unpleasant PM pictures in the recognition task Theoretically , prospect i ve memory retrieval can be accomplished either by controlled monitoring of the environment for a target event or by a more reflexive process that spontaneously responds to the presence of a target event . These views were evaluated in Experiments 1 - 4 by examining whether performing a prospect i ve memory task produced costs on the speed of performing the ongoing task . In Experiment 5 , the authors directly tested for the existence of spontaneous retrieval . The results supported the multiprocess theory ( M. A. McDaniel & G. O. Einstein , 2000 ) predictions that ( a ) spontaneous retrieval can occur and can support good prospect i ve memory and ( b ) depending on task dem and s and individual differences , people rely to different degrees on monitoring versus spontaneous retrieval for prospect i ve remembering The present study investigated the effect of Parkinson ’s disease ( PD ) on prospect i ve memory ( PM ) tasks by varying the emotional content of the PM actions . Twenty-one older adults with PD and 25 healthy older adults took part in the present study . Participants performed three virtual days in the Virtual Week task . On each virtual day , participants performed actions with positive , negative or neutral content . Immediately following each virtual day , participants completed a recognition task to assess their retrospective memory for the various PM tasks . PD patients were less accurate than the control group at both PM accuracy and recognition task accuracy . The effect of emotional valence was also evident , indicating that all participants were more accurate on positive PM tasks than both negative and neutral . This study confirmed PM impairment in PD patients and extended previous research showing how positive emotional stimuli can influence PM performance We investigated whether focal/nonfocal effects ( e.g. , Einstein et al. , 2005 ) in prospect i ve memory ( PM ) are explained by cue differences in monitoring difficulty . In Experiment 1 , we show that syllable cues ( used in Einstein et al. , 2005 ) are more difficult to monitor for than are word cues ; however , initial-letter cues ( in words ) are similar in monitoring difficulty to word cues ( Experiments 2a and 2b ) . Accordingly , in Experiments 3 and 4 , we design ated either an initial letter or a particular word as a PM cue in the context of a lexical decision task , a task that presumably directs attention to focal processing of words but not initial letters . We found that the nonfocal condition was more likely than the focal condition to produce costs to the lexical decision task ( task interference ) . Furthermore , when task interference was minimal or absent , focal PM performance remained relatively high , whereas nonfocal PM performance was near floor ( Experiment 4 ) . Collectively , these results suggest that qualitatively different retrieval processes can support prospect i ve remembering for focal versus nonfocal cues Converging experimental operations and several prospect i ve memory tasks were used across three experiments to determine the extent to which prospect i ve remembering is supported by data driven versus conceptually driven processes . In all experiments , subjects were asked to perform an action when a target item later occurred . When the semantic context changed from encoding to test , prospect i ve memory significantly declined ( Experiment 1 ) . When the target event ( the item , which in its subsequent appearance in the experiment was the signal to perform the action ) was presented as a word ( relative to picture presentation , Experiment 2 ) or was encoded nonsemantically ( relative to semantic encoding , Experiment 3 ) , there was a decline in prospect i ve memory performance . Dividing attention during prospect i ve memory retrieval substantially reduced prospect i ve memory performance ( Experiment 3 ) . The results of this research indicated that prospect i ve memory is largely conceptually driven , and it behaves more similarly to direct rather than indirect conceptual tests . We suggest that prospect i ve remembering of the type studied here is mediated by a reflexive episodic associative memory system as proposed by Moscovitch ( 1994 ) The present study reports test – retest consistency of Virtual Week , a well-known measure of prospect i ve memory ( PM ) performance . PM is the memory associated with carrying out actions at a specific moment in the future . Patients with neurological disorders as well as healthy older adults often report PM dysfunctions that affect their everyday living . In Experiment 1 , 19 younger and 20 older adults undertook the st and ard version of Virtual Week ( version A ) . Older adults showed lower performance compared to younger participants . However , the discrepancy between groups was eliminated at retest . Experiment 2 was conducted to investigate if remembering of PM content determined the improvement observed in older adults at retest in Experiment 1 . To this end we created a parallel version ( version B ) in which we varied the content of the PM actions . Fifty older adults were assigned to one of the two experimental conditions : Version A at test and version B at retest or vice versa ( 25 participants in each condition ) . Results showed no group differences in PM performance between version A and version B ; moreover , no effect of test – retest was found . The study confirmed that Virtual Week is a reliable measure of PM performance and also provided a new parallel version that can be useful in clinical setting Cue saliency is known to influence prospect i ve memory performance , whereby perceptually or conceptually distinct cues facilitate remembering and attenuate adult age-related deficits . The present study investigated whether similar benefits for older adults are also seen for emotional valence . A total of 41 older and 41 younger adults performed a prospect i ve memory task in which the emotional valence of the prospect i ve memory cues was manipulated . Emotionally valenced cues increased prospect i ve memory performance across both groups . Age deficits were only observed when neutral ( but not positive or negative ) prospect i ve cues were presented . Findings are consistent with predictions that salient cues facilitate participants ’ prospect i ve memory performance and reduce age-related differences , while extending the concept of saliency to include emotional valence Emotional factors have been found to be an important influence on memory . The current study investigated the influence of emotional salience and age on a laboratory measure of prospect i ve memory ( PM ) ; Virtual Week . Thirty young and 30 old adults completed Virtual Week , in which the emotional salience of the tasks at encoding was manipulated to be positive , negative or neutral in content . For event-based , but not time-based tasks , positivity enhancement in both age groups was seen , with a greater number of positive PM tasks being performed relative to neutral tasks . There was no negativity enhancement effect . Older adults showed generally poorer levels of PM , but they also demonstrated greater beneficial effects of positive valence compared to young . These effects of emotion on PM accuracy do not appear to reflect the retrospective component of the task as a different pattern of emotion effects was seen on the recall of PM content . Results indicate that older adults ' difficulties in prospect i ve remembering can be reduced where the tasks to be remembered are positive This study investigated the impact of emotional valence on event-based prospect i ve memory performance in depression . Thirty individuals with depression and 29 healthy adults performed a prospect i ve memory task in which the emotional valence of the prospect i ve targets was manipulated ( positive , neutral , negative ) . Collapsed across all valence conditions , healthy adults outperformed individuals with depression in the prospect i ve memory task . This effect was qualified by planned contrasts indicating that the two groups only differed when responding to positively valenced cues , reflecting a positivity effect in healthy adults . These data are in line with previous research , which shows that healthy participants better remember positively valenced cues , but are the first to show an absence of this effect in those with depression Cognitive impairments in multiple sclerosis ( MS ) extend to tasks dem and ing prospect i ve memory ( PM ) : remembering to perform an intended act during ongoing activity . This study investigated whether emotional content influenced the effects of MS on PM , following evidence that emotional valence can influence other aspects of memory . Thirty participants with MS were compared to 30 controls on a PM task , Virtual Week , in which emotion was manipulated . People with MS showed a consistent deficit in PM performance across manipulations of task and valence . Results indicated that emotionally positive tasks improved the PM performance of MS participants , with implication s for rehabilitation While first studies suggested that emotional task material may enhance prospect i ve memory performance in young and older adults , the extent and mechanisms of this effect are under debate . The authors explored possible differential effects of cue valence on the prospect i ve and retrospective component of prospect i ve memory in young and older adults . Forty-five young and 41 older adults performed a prospect i ve memory task in which emotional valence of the prospect i ve memory cue was manipulated ( positive , negative , neutral ) . The multinomial model of event-based prospect i ve memory was used to analyze effects of valence and age on the two prospect i ve memory components separately . Results revealed an interaction indicating that age differences were smaller in both emotional valence conditions . For older adults positive cues improved the prospect i ve component , while negative cues improved the retrospective component . No main effect of valence was found for younger adults on an overt accuracy measure , but model-based analyses showed that the retrospective component was enhanced in the positive compared with the negative cue condition . The study extends the literature in demonstrating that processes underlying emotional effects on prospect i ve memory may differ depending on valence and age Laboratory tests of event-based prospect i ve memory ( ProM ) require participants to perform actions in response to infrequent cues in a background task . We conducted three experiments to assess and improve the reliability of this popular procedure . In Experiment 1 , we tested college students on 2 separate days and found that the alternate-forms reliability of ProM accuracy was quite low ( r = .31 ) , although general knowledge accuracy was more reliable ( r= .89 ) . In Experiment 2 , a statistically significant difference in reliability emerged between conditions with a low ( n = 6 ) versus a high ( n = 30 ) number of ProM targets . Finally , lower ProM accuracy increased reliability in Experiment 3 . Adopting these straightforward changes may enhance the search for individual differences in Acute stress has been found to have negative and implementation intentions ( IIs ) to have positive effects on cognitive performance . This study was the first to examine the effects of IIs on executive action control under acute psychosocial stress . Forty-two male subjects aged 21 - 39 years were r and omly assigned to the Trier Social Stress Test ( TSST ) versus a rest condition . In addition , the instruction to the executive task ( a go no-go task ) was manipulated ( IIs versus st and ard instruction ) . After the stress test , a dual-task procedure including a go no-go task was conducted . The TSST result ed in increases in cortisol response , heart rate and state anxiety compared to the rest condition . Acute stress significantly impaired go no-go performance , but only in the group without IIs . We conclude that under acute stress conditions executive functioning is reduced , but the use of IIs can be an effective strategy to overcome this negative effect Event-based prospect i ve memory tasks require the realisation of a delayed intention at the occurrence of a specific target event . The present research investigates how performance in this kind of prospect i ve memory task is influenced by the current affective state . By manipulating participants ’ mood during intention realisation we tested two competing models of mood effects on memory ( i.e. , a capacity consuming account and a processing style account ) . Furthermore , we manipulated the valence of the target event to investigate mood-congruency effects in prospect i ve memory . No evidence was found for a mood-congruency effect , but the results showed that prospect i ve memory performance increased with a sad mood . This effect is consistent with recent theories on mood-dependent processing-style regulation , postulating that a sad mood produces a more analytic and detailed processing style whereas a happy mood produces a more global and less detailed processing style Previous prospect i ve memory studies have revealed some important features of encoding , retrieval , and the match between the encoding and the retrieval that contribute to prospect i ve memory performance . However , these studies have not provided evidence concerning the relative importance of these three factors because no study has investigated all three in a single design . We developed a laboratory-based paradigm that allowed us to manipulate different characteristics of encoding , retrieval , and the match between encoding and retrieval simultaneously in a single experiment . The results of eight experiments showed that all three factors have an influence on prospect i ve memory performance , but that the match between encoding and retrieval has a significantly larger influence than either encoding or retrieval factors Studies manipulating emotional valence in prospect i ve memory ( PM ) have so far revealed inconsistent results . In the present study , two experiments were conducted to systematic ally disentangle the effects of varying emotional valence in the encoding versus retrieval phase of PM in older adults . Results showed that , while cue valence at retrieval had no influence on PM performance , at encoding both positive and negative valence result ed in reduced PM performance . Findings suggest that emotional valence may have an influence on mnemonic processes at encoding rather than modifying cue detection in aging Prospect i ve memory ( PM ) errors are commonly investigated as failures to execute an intended task ( e.g. , taking medication ) , and some studies suggest that emotional PM cues significantly reduce such failures . In Experiment 1 , we extended these findings and additionally explored whether improved PM performance with emotional cues comes at the expense of performance on the ongoing task . Our results indicated that both younger and older adults are more likely to respond to emotional than to neutral PM cues , but the emotional cues did not differentially disrupt the performance on the ongoing task for either age group . Because older adults are also prone to mistakenly repeating a completed PM task , in Experiment 2 we further examined whether emotional PM cues increased repetition errors for older adults . Despite equivalent opportunity for repetition errors across cue type , older adults committed significantly fewer repetition errors with emotional than with neutral cues . Thus , these experiments demonstrated that older adults can effectively use emotional cues to help them initiate actions and to minimize repetition errors |
13,862 | 21,249,652 | In most of the comparisons there were no significant differences between the treatments under study with regard to cure rates , recurrent infection , incidence of preterm delivery , admission to neonatal intensive care unit , need for change of antibiotic and incidence of prolonged pyrexia .
Although antibiotic treatment is effective for the cure of urinary tract infections , there are insufficient data to recommend any specific drug regimen for treatment of symptomatic urinary tract infections during pregnancy .
All the antibiotics studied were shown to be very effective in decreasing the incidence of the different outcomes .
Complications were very rare . | BACKGROUND Urinary tract infections , including pyelonephritis , are serious complications that may lead to significant maternal and neonatal morbidity and mortality .
There is a large number of drugs , and combination of them , available to treat urinary tract infections , most of them tested in non-pregnant women .
Attempts to define the optimal antibiotic regimen for pregnancy have , therefore , been problematic .
OBJECTIVES The objective of this review was to determine , from the best available evidence from r and omised controlled trials , which agent is the most effective for the treatment of symptomatic urinary tract infections during pregnancy in terms of cure rates , recurrent infection , incidence of preterm delivery and premature rupture of membranes , admission to neonatal intensive care unit , need for change of antibiotic , and incidence of prolonged pyrexia . | Acute pyelonephritis remains a frequent complication of pregnancy . Prevention of the potential complications of this disease requires aggressive in-hospital management . However , the high frequency of positive outpatient cultures following discharge has cast doubt on the adequacy of in-hospital care and , at the same time , has concentrated attention on follow-up care . In a r and omized , prospect i ve study , we evaluated the effects of in-hospital management and outpatient nitrofurantoin on subsequent urine cultures . The overall frequency of positive cultures following discharge from the hospital was 38 % . However , appropriate antibiotic selection , a negative follow-up in-hospital culture and nitrofurantoin suppression reduced the rate to 8 % ( P less than .01 ) . Nitrofurantoin did not reduce the rate of positive cultures if antibiotic selection was inappropriate or if the in-hospital follow-up culture was positive . These results suggest that more aggressive management of acute pyelonephritis in pregnancy may be indicated and that suppressive therapy can not compensate for inappropriate in-hospital management Today , it is widely accepted that a short-course or single-dose treatment with antimicrobial agents in pregnancy is the optimal therapy to minimize the risk of toxicity both for the mother and the fetus . A r and omized trial comparing single-dose ( 3 g ) treatment with fosfomycin trometamol ( FT ) versus pipemidic acid ( 200-gram doses b.i.d . for 7 days ) in bacteriuric pregnant women is presented . The preliminary results show that single-dose FT has the same cure effect as conventional therapy with pipemidic acid A total of 120 patients , including 53 pregnant women with significant bacteriuria , received 163 7-day courses of oral antimicrobial agents allocated in a r and omised manner . The cure rates after 6 weeks ' follow-up ranged from 73 % to 86 % , and there was no statistical difference between preparations of ampicillin , carbenicillin indanyl easter , and 2 different formulations of nifuratel . Side-effects occurred in 30 % to 40 % of the courses of penicillin drugs , but in under 15 % of the course of nifuratel . It is concluded that the new oral preparation of carbenicillin is a useful addition to the list of antimicrobial agents which are effective in the treatment of urinary infections in domiciliary patients . Furthermore , nifuratel has been confirmed as a highly active non-toxic drug which is valuable in the treatment of urinary infections Summary The clinical and bacteriological efficacy and adverse reactions of ofloxacin vs trimethoprim-sulphamethoxazole were investigated in a double-blind , r and omised study in 250 female patients ( 125 in each group ) with acute , uncomplicated lower urinary tract infections . The dosages of ofloxacin and trimethoprim-sulphamethoxazole were 100 mg and 160 mg + 800 mg twice daily , respectively . The duration of therapy was 3 days . 81 % of the patients had significant bacteriuria . Escherichia coli was isolated in 76 % and Staphylococcus saprophyticus in 11 % of the infections . The bacteriological elimination , clinical cure and improvement rates of the evaluable patients on ofloxacin treatment were 92 and 95 % , respectively . The corresponding figures on trimethoprim-sulphamethoxazole therapy were 88 and 90 % . Adverse reactions were clinical ly unimportant , and none of the patients had to stop treatment . Mild and transient side effects , mainly from the gastrointestinal tract , central nervous system and skin , were reported by 19 and 22 % of the patients in the ofloxacin and trimethoprim-sulphamethoxazole groups , respectively . None of the differences in clinical and bacteriological efficacy and side effects of ofloxacin vs trimethoprim-sulphamethoxazole were statistically significant . Ofloxacin appears to be an appropriate antibiotic for short term therapy of acute , uncomplicated , lower urinary , tract infections , comparing favourably with trimethoprim-sulphamethoxazole treatment in this study |
13,863 | 25,548,525 | For all primary chemotherapy agents , use of carboplatin is associated with slightly higher costs than cisplatin . | During these last years , there have been an increased number of new drugs for non-small cell lung cancer ( NSCLC ) , with a growing financial effect on patients and society .
The purpose of this article was to review the economics of first-line and maintenance NSCLC treatments .
We review ed economic analyses of NSCLC therapies published between 2004 and 2014 .
In first-line setting s , in unselected patients with advanced NSCLC , the cisplatin gemcitabine doublet appears to be cost-saving compared with other platinum doublets . | Background The median age of newly diagnosed patients with non-small cell lung cancer ( NSCLC ) is 67 years , and one-third of patients are older than 75 years . Elderly patients are more vulnerable to the adverse effects of chemotherapy , and targeted therapy might thus be a relevant alternative . The objective of this study was to assess the cost-effectiveness of erlotinib followed by chemotherapy after progression , compared to the reverse strategy , in fit elderly patients with advanced NSCLC participating in a prospect i ve r and omized phase 2 trial ( GFPC0504 ) . Methods Outcomes ( PFS and overall survival ) and costs ( limited to direct medical costs , from the third-party payer perspective ) were prospect ively collected until second progression . Costs after progression and health utilities ( based on disease states and grade 3–4 toxicities ) were derived from the literature . Results Median overall survival , QALY and total costs for the erlotinib-first strategy were respectively 7.1 months , 0.51 and 27 734 € , compared to 9.4 months , 0.52 and 31 688 € for the chemotherapy-first strategy . The Monte Carlo simulation demonstrates that the two strategies do not differ statistically . Conclusion In terms of cost effectiveness , in fit elderly patients with NSCLC , erlotinib followed by chemotherapy compares well with the reverse strategy OBJECTIVES A recent r and omized study showed switch maintenance with pemetrexed after nonpemetrexed-containing first-line chemotherapy in patients with advanced nonsmall-cell lung cancer to prolong overall survival by 2.8 months . We examined the cost-effectiveness of pemetrexed in this indication , from the perspective of the Swiss health care system , and assessed the influence of the costs of best supportive care ( BSC ) on overall cost-effectiveness . METHODS A Markov model was constructed based on the pemetrexed maintenance study , and the incremental cost-effectiveness ratio ( ICER ) of adding pemetrexed until disease progression was calculated as cost per quality -adjusted life-year gained . Uncertainties concerning the costs of BSC on the ICER were addressed . RESULTS The base case ICER for maintenance therapy with pemetrexed plus BSC compared to BSC alone was € 106,202 per quality -adjusted life-year gained . Varying the costs for BSC had a marked effect . Assuming a reduction of the costs for BSC by 25 % in the pemetrexed arm result ed in an ICER of € 47,531 per quality -adjusted life-year , which is below predefined criteria for cost effectiveness in Switzerl and . CONCLUSIONS Switch maintenance with pemetrexed in patients with advanced nonsquamous-cell lung cancer after st and ard first-line chemotherapy is not cost-effective . Uncertainties on the re source use and costs for BSC have a large influence on the cost-effectiveness calculation and should be reported in more detail BACKGROUND / OBJECTIVE Non-platinum-based chemotherapy is a potential alternative to platinum doublet therapy for advanced non-small cell lung cancer in selected patients . We determined the cost-effectiveness of gemcitabine/vinorelbine ( GEMVIN ) , versus cisplatin/gemcitabine ( PG ) or cisplatin/vinorelbine ( PV ) , from a government payer perspective . METHODS Results from a r and omized trial of GEMVIN versus PG or PV demonstrated no significant difference in global quality of life ( primary endpoint ) or overall survival between regimens , but superior progression-free survival for platinum-based regimens . A cost analysis was conducted using direct medical costs of treatment , grade 3 or 4 toxicity management , and investigations for the mean number of cycles per study arm . Costs were calculated using Canadian dollars in 2005 , and then in 2013 after drug patent expiry . RESULTS In 2005 , GEMVIN was the most expensive regimen ( $ 6868 ) , and PV the least expensive ( $ 4650 ) , with an incremental cost of GEMVIN over PV of $ 2218 . Diagnostic and administration costs did not differ significantly among regimens ; GEMVIN had the lowest toxicity costs . The principal cost driver in 2005 was the cost of chemotherapy . In 2013 , toxicity and administration costs emerged as major drivers ; GEMVIN was less costly than PV and PG , ( cost savings of $ 413 over PV ) . CONCLUSION Despite similar outcomes , GEMVIN was more expensive than PV or PG in 2005 because of higher chemotherapy costs . By 2013 , after chemotherapy drug patent expiry , GEMVIN became the least costly regimen . Economic considerations in oncology change over time , and should be revisited in policy decisions based on cost Background Platinum-doublet , first-line treatment of locally advanced or metastatic non-small cell lung cancer ( NSCLC ) is limited to 4–6 cycles . An alternative strategy used to prolong the duration of first-line treatment and extend survival in metastatic NSCLC is first-line maintenance therapy . Erlotinib was approved for first-line maintenance in a stable disease population following results from a r and omized , controlled Phase III trial comparing erlotinib with best supportive care . We aim ed to estimate the incremental cost-effectiveness of erlotinib 150 mg/day versus best supportive care when used as first-line maintenance therapy for patients with locally advanced or metastatic NSCLC and stable disease . Methods An economic decision model was developed using patient-level data for progression-free survival and overall survival from the SATURN ( SequentiAl Tarceva in UnResectable NSCLC ) study . An area under the curve model was developed ; all patients entered the model in the progression-free survival health state and , after each month , moved to progression or death . A time horizon of 5 years was used . The model was conducted from the perspective of national health care payers in France , Germany , and Italy . Probabilistic sensitivity analyses were performed . Results Treatment with erlotinib in first-line maintenance result ed in a mean life expectancy of 1.39 years in all countries , compared with a mean 1.11 years with best supportive care , which represents 0.28 life-years ( 3.4 life-months ) gained with erlotinib versus best supportive care . In the base-case analysis , the cost per life-year gained was € 39,783 , € 46,931 , and € 27,885 in France , Germany , and Italy , respectively . Conclusion Erlotinib is a cost-effective treatment option when used as first-line maintenance therapy for locally advanced or metastatic NSCLC Introduction Lung cancer , the most prevalent malignant cancer in the world , remains a serious threat to public health . Recently , a large number of studies have shown that an epidermoid growth factor receptor-tyrosine kinase inhibitor ( EGFR TKI ) , Erlotinib , has significantly better efficacy and is better tolerated in advanced non-small cell lung cancer ( NSCLC ) patients with a positive EGFR gene mutation . However , access to this drug is severely limited in China due to its high acquisition cost . Therefore , we decided to conduct a study to compare cost-effectiveness between erlotinib monotherapy and carboplatin-gemcitabine ( CG ) combination therapy in patients with advanced EGFR mutation-positive NSCLC . Methods A Markov model was developed from the perspective of the Chinese health care system to evaluate the cost-effectiveness of the two treatment strategies ; this model was based on data from the OPTIMAL trial , which was undertaken at 22 centres in China . The 10-year quality -adjusted life years ( QALYs ) , direct costs , and incremental cost-effectiveness ratio ( ICER ) were estimated . To allow for uncertainties within the parameters and to estimate the model robustness , one-way sensitivity analysis and probabilistic sensitivity analysis were performed . Results The median progression-free survival ( PFS ) obtained from Markov model was 13.2 months ( 13.1 months was reported in the trial ) in the erlotinib group while and 4.64 months ( 4.6 months was reported in the trial ) in the CG group . The QALYs were 1.4 years in the erlotinib group and 1.96 years in the CG group , indicating difference of 0.56 years . The ICER was most sensitive to the health utility of DP ranged from $ 58,584.57 to $ 336,404.2 . At a threshold of $ 96,884 , erlotinib had a 50%probability of being cost-effective . Conclusions Erlotinib monotherapy is more cost-effective compared with platinum-based doublets chemotherapy as a first-line therapy for advanced EGFR mutation- positive NSCLC patients from within the Chinese health care system OBJECTIVE To compare the effectiveness and cost-effectiveness of erlotinib versus gefitinib as first-line treatment of epidermal growth factor receptor-activating mutation-positive non-small-cell lung cancer patients . DESIGN . Indirect treatment comparison and a cost-effectiveness assessment . SETTING Hong Kong . PATIENTS Those having epidermal growth factor receptor-activating mutation-positive non-small-cell lung cancer . INTERVENTIONS Erlotinib versus gefitinib use was compared on the basis of four relevant Asian phase-III r and omised controlled trials : one for erlotinib ( OPTIMAL ) and three for gefitinib ( IPASS ; NEJGSG ; WJTOG ) . The cost-effectiveness assessment model simulates the transition between the health states : progression-free survival , progression , and death over a lifetime horizon . The World Health Organization criterion ( incremental cost-effectiveness ratio <3 times of gross domestic product/capita : < US$ 102 582 ; approximately < HK$798 078 ) was used to rate cost-effectiveness . RESULTS The best fit of study characteristics and prognostic patient characteristics were found between the OPTIMAL and IPASS trials . Comparing progression-free survival hazard ratios of erlotinib versus gefitinib using only these r and omised controlled trials in an indirect treatment comparison result ed in a statistically significant progression-free survival difference in favour of erlotinib ( indirect treatment comparison hazard ratio=0.33 ; 95 % confidence interval , 0.19 - 0.58 ; P=0.0001 ) . The cost-effectiveness assessment model showed that the cost per progression-free life year gained and per quality -adjusted life year gained was at acceptable values of US$ 39 431 ( approximately HK$306 773 ) and US$ 62 419 ( approximately HK$485 619 ) for erlotinib versus gefitinib , respectively . CONCLUSION The indirect treatment comparison of OPTIMAL versus IPASS shows that erlotinib is significantly more efficacious than gefitinib . Furthermore , the cost-effectiveness assessment indicates that the incremental cost-effectiveness ratios are well within an acceptable range in relation to the survival benefits obtained . In conclusion , erlotinib is cost-effective compared to gefitinib for first-line epidermal growth factor receptor-activating mutation-positive non-small-cell lung cancer patients Abstract Background : During the 1990s , a number of new cytotoxic agents with clinical ly relevant activity in non-small-cell lung cancer ( NSCLC ) , and with a more favourable therapeutic index than drugs already in use , became available . Given the high prices of these new drugs and the large number of patients affected , it is important to compare the relative benefits and costs of these treatments with the existing regimens before treatment policy decisions are changed . Purpose : An economic evaluation of three different regimens of chemotherapy in patients with advanced NSCLC was performed from the perspective of the Dutch health insurance system using tariffs valid for 2002 . The economic evaluation was integrated into a phase III clinical trial in which the reference regimen cisplatinpaclitaxel was compared with two experimental regimens : cisplatin-gemcitabine and gemcitabine-paclitaxel . Material s and methods : Unit costs were applied to re source use data collected prospect ively on case report forms during the trial . The average total ( uncensored ) cost per patient was determined for each of the treatment groups . The principal outcome measure for the economic evaluation was the estimated mean survival time per treatment group . This outcome was then incorporated into incremental cost-effectiveness ratios based on costs corrected for censoring . The impact of uncertainty was assessed by bootstrap techniques , and the analysis and interpretation of the data focused on the bivariate density of differences in outcomes and costs in the incremental cost-effectiveness plane . The final results were summarised by the derivation of cost-effectiveness acceptability curves . Results : The estimated mean survival time was equivalent in the two cisplatinbased regimens with largely overlapping confidence intervals . There was a 99 % probability that cisplatin-gemcitabine is the least costly regimen of the two and a 72 % probability that this regimen reduces costs while at the same time improving survival . Compared with cisplatin-paclitaxel , the gemcitabine-paclitaxel regimen engendered a borderline significant reduction in mean survival time combined with an almost 90 % probability of an increase in costs . Conclusion : The two cisplatin-based regimens are equivalent in terms of survival , but cisplatin-gemcitabine may reduce costs by approximately € 2000 per patient compared with cisplatin-paclitaxel . Gemcitabine-paclitaxel is a dominated option with higher costs and a reduction in mean survival time compared with cisplatinpaclitaxel BACKGROUND A large proportion of elderly patients ( > 70 years ) with newly diagnosed NSCLC are shown to be frail by a comprehensive geriatric assessment . This population is more vulnerable to adverse effects of chemotherapy and might thus benefit more from targeted therapy . The objective of this study was to assess the cost-effectiveness of erlotinib followed by chemotherapy after progression , compared with the reverse strategy , in frail elderly patients with advanced NSCLC participating in a prospect i ve r and omized phase II trial ( GFPC 0505 ) . MATERIAL S AND METHODS Outcomes ( progression-free survival and overall survival ) and costs ( limited to direct medical costs , from the third-party payer perspective ) were collected prospect ively until second progression . Costs after progression and health utilities ( based on disease states and grade 3 - 4 toxicities ) were derived from the literature . RESULTS Median overall survival , QALYs , and total costs for the erlotinib-first strategy were 3.9 months , 0.33 , and € 15,233 , respectively , compared with 4.4 months , 0.35 , and € 15,363 for the chemotherapy-first strategy . There was no significant difference between the 2 strategies in term of cost-effectiveness ( respectively € 47,381 and € 44,350 per QALY ) . CONCLUSION No difference in cost-effectiveness was found between an erlotinib-first strategy and a chemotherapy-first strategy in frail elderly patients with NSCLC Introduction : To estimate the cost-effectiveness of first-line cisplatin/pemetrexed ( Cis/Pem ) compared with cisplatin/gemcitabine ( Cis/Gem ) , carboplatin/paclitaxel ( Carb/Pac ) , and carboplatin/paclitaxel/bevacizumab ( Carb/Pac/Bev ) in patients with advanced non-small cell lung cancer ( NSCLC ) , particularly in those with nonsquamous cell histology ( i.e. , adenocarcinoma , large cell carcinoma , or histology not otherwise specified ) . Methods : A semi-Markov model was developed to compare the 2-year impact of Cis/Pem to three other first-line regimens from the U.S. payer perspective . Data from the r and omized controlled clinical trial of Cis/Pem versus Cis/Gem and a mixed treatment comparison model ( no head-to-head data were available for the Cis/Pem to Carb/Pac or Carb/Pac/Bev comparisons ) provided clinical inputs . Medicare reimbursement rates were used to determine drug costs . A retrospective cl aims data base analysis was used to obtain estimates of other direct NSCLC-related costs . Results : In all patients with advanced NSCLC regardless of histologic subtype , using Cis/Pem as first-line chemotherapy led to an incremental cost per life-year gained ( LYG ) of $ 104,577 for Cis/Pem to Cis/Gem and $ 231,291 for Cis/Pem to Carb/Pac . In the prespecified subset of patients with nonsquamous cell histology , the incremental cost per LYG was $ 83,537 for Cis/Pem to Cis/Gem and $ 178,613 for Cis/Pem to Carb/Pac . The incremental cost per LYG for Carb/Pac/Bev to Cis/Pem was more than $ 300,000 . Conclusions : Compared with commonly used and reimbursed regimens for first-line chemotherapy in advanced NSCLC , Cis/Pem may be considered cost-effective , particularly in patients with nonsquamous cell histology . This analysis emphasizes the importance of histology in identifying the appropriate patient for Cis/Pem first-line chemotherapy OBJECTIVES Economic evaluations of chemotherapy regimens for stage IIIB or IV non-small cell lung cancer ( NSCLC ) have been conducted for many European countries , but not for Portugal . This study evaluates the total health care costs of five commonly used doublet regimens with similar efficacy results . METHODS Using the methodology reported by Schiller [ Schiller JH , Tilden D , Aristides M , Lees M , Kielhorn A , Maniadakis N , et al. Restropective cost analysis of gemcitabine in combination with cisplatin in non-small cell lung cancer compared to other combination therapies in Europe . Lung Cancer 2004;43:101 - 12 ] , we conducted a cost-minimization analysis to compare vinorelbine-cisplatin ( Vin/Cis ) , gemcitabine-cisplatin ( Gem/Cis ) , paclitaxel-carboplatin ( Pac/Carb ) , docetaxel-cisplatin ( Doc/Cis ) , and paclitaxel-cisplatin ( Pac/Cis ) . The perspective was that of the Portuguese National Health Service and included only direct medical costs ( reimbursed costs plus co-payments ) : chemotherapy acquisition , chemotherapy administration , hospitalizations due to adverse events , and other medical re sources . Unit costs were drawn from official sources ( Diagnosis Related Groups and retail/hospital costs ) ( 2003 value [ Diagnosis Related Groups ( DRG ) published at Diário da República ; 2003 ] ) . Re source use was estimated from two multicenter r and omized phase III trials [ Comella P , Frasci G , Panza N , Manzione L , De Cataldis G , Cioffi R , et al. R and omized trial comparing cisplatin , gemcitabine , and vinorelbine with either cisplatin and gemcitabine or cisplatin and vinorelbine in advanced non-small-cell lung cancer : interim analysis of a phase III trial of the Southern Italy Cooperative Oncology Group . J Clin Oncol 2000;18:1451 - 7 ; Schiller JH , Harrington D , Belani CP , Langer C , S and ler A , Krook J , et al. Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer . N Engl J Med 2002;346:92 - 8 ] . A time horizon of a full course of therapy was adopted . One-way sensitivity analyses were performed . RESULTS The least and the most costly chemotherapy regimens were Gem/Cis and Pac/Carb , respectively . Total mean cost per patient was estimated at euro7083 for Gem/Cis and euro10,008 for Pac/Carb , a mean cost savings of euro2925 per patient for Gem/Cis . The differences were mainly due to the higher chemotherapy acquisition costs of Pac/Carb than for Gem/Cis . Gem/Cis was less costly in all sensitivity analyses except when 100 % inpatient chemotherapy administration was assumed . CONCLUSION Gem/Cis should be considered as a cost-saving alternative to the other four regimens in treating NSCLC patients in Portugal In two recent r and omised trials , gemcitabine plus cisplatin ( Gem/Cis ) was found to be at least as effective as vinorelbine plus cisplatin ( Vin/Cis ) , paclitaxel plus cisplatin ( Pac/Cis ) , paclitaxel plus carboplatin ( Pac/Carbo ) , or docetaxel plus cisplatin ( Doc/Cis ) in patients with advanced non-small cell lung cancer ( NSCLC ) . In cost-minimisation analyses of these studies from the perspectives of the national health services of five European countries ( France , Germany , Italy , Spain , UK ) , Gem/Cis was associated with lower average treatment-related costs than Vin/Cis , Pac/Cis , and Pac/Carbo , and similar or lower costs than Doc/Cis . The incremental cost savings per patient of Gem/Cis compared to Vin/Cis ranged from 827 Euro to 2055 Euro per patient and from 1616 Euro to 5342 Euro compared to the paclitaxel-containing regimens . Overall , results were generally similar between countries , and were robust to univariate sensitivity analyses . Although differences in healthcare systems mean that the results may not be generalisable to all countries/ setting s , these results provide an economic rationale for the use of Gem/Cis as a first-line treatment option in Europe for patients with NSCLC The UK National Institute for Health and Clinical Excellence ( NICE ) invited the manufacturer of erlotinib ( Roche ) to su bmi t evidence for the clinical and cost effectiveness of erlotinib as monotherapy for the maintenance treatment of patients with non-small cell lung cancer ( NSCLC ) and stable disease following previous treatment with four cycles of platinumcontaining therapy . The Liverpool Review s and Implementation Group(LRiG ) at the University of Liverpool was commissioned to act as the Evidence Review Group ( ERG ) for this appraisal .The ERG review ed the clinical - and cost-effectiveness evidence in two stages and in accordance with the decision problem defined by NICE . The analysis of the su bmi tted models assessed the appropriateness of the approach taken by the manufacturer in modelling the decision problem . Analysis also included reliability of model implementation and the extent of conformity to published st and ards and prevailing norms of practice within the health economics modelling community . Particular attention was paid to issues likely to have substantial impact on the base-case cost-effectiveness results . Clinical evidence was derived from a multi-centre , double-blind , r and omized , phase III study design ed to address the overall population of NSCLC patients . Outcomes included progression-free survival ( PFS ) and overall survival ( OS ) . The recruited population was mainly from outside of Western Europe and no patients in the pivotal trial had received pemetrexed as a firstline therapy , which is now accepted clinical practice in the UK . The evidence considered in this article includes only the population for whom marketing authorizations has been received – that is , patients with stable disease following first-line therapy . The trial reported a small but statistically significant increase in both PFS and OS in patients with stable disease receiving erlotinib compared with placebo . However , no significant difference was identified in OS when patients with non-squamous disease and stable disease were considered as a subgroup . The economic evidence was focussed on the ERG ’s assessment of three economic models that related to patients with stable disease and compared erlotinib with placebo in the squamous and non-squamous population s and erlotinib with pemetrexed in the non-squamous population . The incremental cost-effectiveness ratios ( ICERs ) reported by the manufacturer were £ 39 936 per QALY gained ( stable disease , all ) ; £ 35 491 per QALY gained ( stable disease , squamous ) ; and £ 40 020 per QALY gained ( stable disease , nonsquamous ) . In comparison with pemetrexed , in the cases where erlotinib was considered to be superior or equivalent , erlotinib dominated . In the cases where erlotinib was considered to be slightly inferior , then the ICERs ranged between £ 91 789 and £ 511 351 per QALY gained ; these ICERs appear in the south-west corner of a cost-effectiveness plane , i.e. erlotinib is cheaper but less effective than pemetrexed . The ERG recalculated the base-case cost-effectiveness results in the manufacturer ’s su bmi ssion , considering nine key areas where corrections and /or adjustments were required , related to time horizon , discounting logic , costs of erlotinib and pemetrexed , cost of second-line chemotherapy , unit costs , utility values , PFS and OS . This result ed in ERG-revised ICERs for the stable disease squamous population of £ 44 812 per QALY gained , in the stable disease non-squamous population of £ 68 120 per QALY gained , and , when erlotinib was compared with pemetrexed , the result was £ 84 029 per QALY gained . All values were above NICE ’s perceived willingness-to-pay threshold . After the second Appraisal Committee meeting , the Committee did not recommend the use of erlotinib in this patient population OBJECTIVES Bevacizumab is approved for treatment of advanced non-small cell lung cancer ( NSCLC ) in combination with chemotherapy based on a 2-month median survival benefit demonstrated in one r and omized trial . The cost-utility of adding bevacizumab to chemotherapy in advanced NSCLC remains unknown . We evaluated the cost-utility of bevacizumab added to chemotherapy in patients with advanced NSCLC . METHODS We developed a Markov model to estimate quality -adjusted life years ( QALYs ) and direct medical costs from the US payer perspective in patients treated with bevacizumab plus chemotherapy and compared these outcomes with patients treated with chemotherapy alone . We populated the model with survival and toxicity data from the clinical trial that compared the two strategies . We obtained utilities from a literature search and unit costs from Medicare . We discounted QALYs and costs at 3 % per year . We addressed uncertainty with one-way and probabilistic sensitivity analyzes . RESULTS Compared with chemotherapy alone , bevacizumab and chemotherapy increased mean QALYs by 0.13 , at an incremental life-time cost of US$ 72,000 per patient . The incremental cost-utility ratio ( ICUR ) was US$ 560,000/QALY . The ICUR was most sensitive to the survival on bevacizumab treatment , the drug costs of bevacizumab , and the utility of stable disease on treatment . At a threshold of US$ 100,000/QALY , the addition of bevacizumab had a 0.2 % probability of being cost-effective . CONCLUSIONS Bevacizumab does not appear to be cost-effective when added to chemotherapy in patients with advanced NSCLC , based on approximate cost-effectiveness thresholds that have been identified in the United States . These results may inform decision-makers about re source allocation for NSCLC care A retrospective cost-minimisation analysis was conducted comparing novel chemotherapies for the treatment of chemo-naive patients with locally advanced , recurrent , and /or metastatic non-small cell lung cancer ( NSCLC ) . Re source use information was obtained from a Phase III r and omised trial investigating the efficacy and toxicity of gemcitabine/cisplatin ( Gem/Cis ) , paclitaxel/carboplatin ( Pac/Carbo ) and vinorelbine/cisplatin ( Vin/Cis ) combination regimens in 612 patients with advanced NSCLC . Since there were no statistically significant differences between the three treatments in terms of progression-free or overall survival in this trial , a cost-minimisation analysis was considered to be the appropriate type of economic evaluation . The perspective was that of the national healthcare provider in Italy . Medical re source use was obtained from the clinical trial data base , from which mean cost streams were calculated for each treatment group . The mean total treatment costs per patient were 8094 euros , 11,203 euros and 9320 euros for the Gem/Cis , Pac/Carbo and Vin/Cis regimens , respectively . Based on re source consumption in a clinical trial , Gem/Cis had the lowest overall mean costs of the three chemotherapy regimens . Gem/Cis therefore has the potential to save costs in the treatment of advanced NSCLC in Italy Introduction : The primary objective was to estimate the cost-effectiveness of maintenance therapy with pemetrexed ( Pem ) compared with observation , each with best supportive care , in patients with advanced non-small cell lung cancer ( NSCLC ) who have completed , without progression , at least four cycles of first-line platinum chemotherapy , particularly in those with nonsquamous cell histology . Secondary comparisons included Pem with erlotinib ( Erl ) or Pem with bevacizumab ( Bev ) . Methods : A semi-Markov model was developed to compare the 3-year impact of Pem with three other alternatives for maintenance therapy from a United States payer perspective . Data from r and omized controlled clinical trials provided clinical inputs . Medicare reimbursement rates were used to determine drug costs . A retrospective cl aims data base analysis was used to obtain estimates of other direct NSCLC-related costs . Results : In the prespecified subset of patients with nonsquamous cell histology only , the incremental cost per life-year gained was $ 122,371 for Pem to observation and $ 150,260 for Pem to Erl , and Bev was dominated by Pem . In all patients with advanced NSCLC regardless of histologic subtype , using Pem as maintenance therapy led to an incremental cost per life-year gained of $ 205,597 compared with observation and $ 312,341 compared with Erl . Conclusions : Compared with observation and other agents used and /or reimbursed for maintenance therapy in advanced NSCLC , Pem may be considered cost-effective , particularly in patients with nonsquamous cell histology . This analysis is the first to evaluate the cost-effectiveness of maintenance therapy in advanced NSCLC and emphasizes the importance of histology in identifying the appropriate patient for Pem maintenance therapy |
13,864 | 27,060,875 | The current evidence supports a beneficial impact of mobile phone-based smoking cessation interventions on six-month cessation outcomes . | BACKGROUND Access to mobile phones continues to increase exponentially globally , outstripping access to fixed telephone lines , fixed computers and the Internet .
Mobile phones are an appropriate and effective option for the delivery of smoking cessation support in some context s. This review up date s the evidence on the effectiveness of mobile phone-based smoking cessation interventions .
OBJECTIVES To determine whether mobile phone-based smoking cessation interventions increase smoking cessation in people who smoke and want to quit . | Objective : To assess the efficacy of an innovative smoking cessation intervention targeted to a multiethnic , economically disadvantaged HIV-positive population . Design : A two-group r and omized clinical trial compared a smoking cessation intervention delivered by cellular telephone with usual care approach . Methods : Current smokers from a large , inner city HIV/AIDS care center were recruited and r and omized to receive either usual care or a cellular telephone intervention . The usual care group received brief physician advice to quit smoking , targeted self-help written material s and nicotine replacement therapy . The cellular telephone intervention received eight counseling sessions delivered via cellular telephone in addition to the usual care components . Smoking-related outcomes were assessed at a 3-month follow-up . Results : The trial had 95 participants and 77 ( 81.0 % ) completed the 3-month follow-up assessment . Analyses indicated biochemically verified point prevalence smoking abstinence rates of 10.3 % for the usual care group and 36.8 % for the cellular telephone group ; participants who received the cellular telephone intervention were 3.6 times ( 95 % confidence interval , 1.3 - 9.9 ) more likely to quit smoking compared with participants who received usual care ( P = 0.0059 ) . Conclusions : These results suggest that individuals living with HIV/AIDS are receptive to , and can be helped by , smoking cessation treatment . In addition , smoking cessation treatment tailored to the special needs of individuals living with HIV/AIDS , such as counseling delivered by cellular telephone , can significantly increase smoking abstinence rates over that achieved by usual care Background Advances in technology allowed the development of a novel smoking cessation program delivered by video messages sent to mobile phones . This social cognitive theory-based intervention ( called “ STUB IT ” ) used observational learning via short video diary messages from role models going through the quitting process to teach behavioral change techniques . Objective The objective of our study was to assess the effectiveness of a multimedia mobile phone intervention for smoking cessation . Methods A r and omized controlled trial was conducted with 6-month follow-up . Participants had to be 16 years of age or over , be current daily smokers , be ready to quit , and have a video message-capable phone . Recruitment targeted younger adults predominantly through radio and online advertising . Registration and data collection were completed online , prompted by text messages . The intervention group received an automated package of video and text messages over 6 months that was tailored to self-selected quit date , role model , and timing of messages . Extra messages were available on dem and to beat cravings and address lapses . The control group also set a quit date and received a general health video message sent to their phone every 2 weeks . Results The target sample size was not achieved due to difficulty recruiting young adult quitters . Of the 226 r and omized participants , 47 % ( 107/226 ) were female and 24 % ( 54/226 ) were Maori ( indigenous population of New Zeal and ) . Their mean age was 27 years ( SD 8.7 ) , and there was a high level of nicotine addiction . Continuous abstinence at 6 months was 26.4 % ( 29/110 ) in the intervention group and 27.6 % ( 32/116 ) in the control group ( P = .8 ) . Feedback from participants indicated that the support provided by the video role models was important and appreciated . Conclusions This study was not able to demonstrate a statistically significant effect of the complex video messaging mobile phone intervention compared with simple general health video messages via mobile phone . However , there was sufficient positive feedback about the ease of use of this novel intervention , and the support obtained by observing the role model video messages , to warrant further investigation . Trial registration Australian New Zeal and Clinical Trials Registry Number : ACTRN12606000476538 ; http://www.anzctr.org.au/trial_view.aspx?ID=81688 ( Archived by WebCite at http://www.webcitation.org/5umMU4sZi Summary We evaluated the effectiveness of a mobile phone text-messaging based smoking cessation intervention package among Chinese adolescent smokers . Students aged 16–19 years were recruited from six vocational high schools located in Shanghai . We assigned the six schools to an intervention group or a control group by cluster r and omization . The 92 participants in the intervention group were given tailored information via mobile phone text-messaging for 12 weeks . The 87 participants in the control group were provided with a self-help pamphlet about smoking cessation instead . After the intervention , attitudes towards the disadvantages of smoking were significantly improved , and the level of nicotine dependence and cigarette dependence significantly decreased in the intervention group . The intervention group had a relatively higher self-reported 7-day abstinence compared to the control group and 30-day abstinence , but the differences were not significant . However , the intervention group had a significantly higher rate of smoking reduction ( 66 % vs. 35 % ) and moving forward in quitting stages ( 52 % vs. 18 % ) compared to the control group . The interactive and tailored assistance provided by the mobile phone text-messaging was effective in smoking behaviour intervention in Chinese adolescent smokers Mounting evidence suggests that smokers living with HIV/AIDS have a significantly increased risk of numerous adverse health outcomes ( both AIDS- and non-AIDS-related ) compared with HIV-positive nonsmokers . Therefore , efforts to design and implement effective cessation programs for this ever-growing special population are warranted . The present study assessed the effects of a cell phone intervention ( CPI ) on hypothesized mediators ( i.e. , changes in depression , anxiety , social support , and self-efficacy ) demonstrated to influence cessation outcomes in other population s. Ninety-five participants from an inner-city AIDS clinic were r and omized to receive either the CPI or recommended st and ard of care ( RSOC ) smoking cessation treatment . Participants r and omized to the RSOC group ( n=47 ) received brief advice to quit , a 10-week supply of nicotine patches , and self-help material s. Participants r and omized to the CPI group ( n=48 ) received RSOC components plus a series of eight proactive counseling sessions delivered via cell phones . A series of regression analyses ( linear and logistic ) was used to assess the relationships between treatment group , the hypothesized mediators , and biochemically confirmed smoking cessation outcomes . Results indicated that the CPI group experienced greater reductions in anxiety and depression , and increases in self-efficacy compared with the RSOC group . Further , changes in depression , anxiety , and self-efficacy weakened the association between treatment group and cessation outcome . The mediator hypothesis , however , for social support was rejected , as the difference score was not significantly associated with treatment group . These results suggest that the efficacy of the CPI is at least partially mediated by its ability to decrease symptoms of distress while increasing self-efficacy Background Although supporting lifestyle change is an effective way of preventing further events in people with cardiovascular disease , providing access to such interventions is a major challenge . This study aims to investigate whether simple reminders about behaviour change sent via mobile phone text message decrease cardiovascular risk . Methods and analysis R and omised controlled trial with 6 months of follow-up to evaluate the feasibility , acceptability and effect on cardiovascular risk of repeated lifestyle reminders sent via mobile phone text messages compared to usual care . A total of 720 patients with coronary artery disease will be r and omised to either st and ard care or the TEXT ME intervention . The intervention group will receive multiple weekly text messages that provide information , motivation , support to quit smoking ( if relevant ) and recommendations for healthy diets and exercise . The primary end point is a change in plasma low-density lipoprotein cholesterol at 6 months . Secondary end points include a change in systolic blood pressure , smoking status , quality of life , medication adherence , waist circumference , physical activity levels , nutritional status and mood at 6 months . Process outcomes related to acceptability and feasibility of TEXT ME will also be collected . Ethics and dissemination Primary ethics approval was received from Western Sydney Local Health Network Human Research Ethics Committee — Westmead . Results will be disseminated via the usual scientific forums including peer- review ed publications and presentations at international conferences . Clinical trials registration number ACTRN12611000161921 INTRODUCTION Substantial evidence indicates that cigarette smoking among people living with HIV/AIDS ( PLWHA ) represents a significant public health concern . However , few efforts to assess smoking cessation interventions targeting this population have been reported . In this brief report , 3-month outcomes from an ongoing treatment trial for PLWHA who smoke are described . METHODS Study participants were recruited from a large HIV care center serving a diverse population of PLWHA . A two-group r and omized design was used to compare the efficacy of usual-care ( UC ) smoking cessation treatment versus a cell phone intervention ( CPI ) . Follow-ups were conducted at the HIV clinic 3 months postenrollment . Using an intent-to-treat approach , a series of multiple regression models were used to compare smoking outcomes in the 2 groups . RESULTS Four hundred and seventy-four participants were enrolled and r and omized , UC ( n = 238 ) and CPI ( n = 236 ) . Mean age in the sample was 44.8 ( SD = 8.1 ) years , and the majority were male ( 70.0 % ) , Black ( 76.6 % ) , and had an education level of high school or less ( 77.5 % ) . At follow-up , participants in the CPI group were 4.3 ( 95 % CI = 1.9 , 9.8 ) times more likely to be abstinent ( 7 day ) compared with those in the UC group . Similarly , significant point estimates were observed for the other smoking outcomes of interest . CONCLUSIONS Findings from this preliminary report indicate that a smoking cessation intervention for PLWHA consisting of cell phone-delivered proactive counseling results in significantly higher abstinence rates compared with a st and ard care approach . Evaluation of the long-term ( 6-month and 12-month ) efficacy of the CPI approach is ongoing Background The study aims to test the differential effects of a web-based text and a web-based video-driven computer-tailored approach for lower socio-economic status ( LSES ) and higher socio-economic status ( HSES ) smokers which incorporate multiple computer-tailored feedback moments . The two programs differ only in the mode of delivery ( video- versus text-based messages ) . The paper aims to describe the development and design of the two computer-tailored programs . Methods / design Respondents who smoked at the time of the study inclusion , who were motivated to quit within the following six months and who were aged 18 or older were included in the program . The study is a r and omized control trial with a 2 ( video/text ) * 2(LSES/HSES ) design . Respondents were assigned either to one of the intervention groups ( text versus video tailored feedback ) or to the control group ( non-tailored generic advice ) . In all three conditions participants were asked to fill in the baseline question naire based on the I-Change model . The question naire assessed socio-demographics , attitude towards smoking , knowledge , self-efficacy , social influence , depression , level of addiction , action planning , goal actions , intention to quit smoking , seven-day point prevalence and continued abstinence . Follow-up measurements were conducted at six and twelve months after baseline . Discussion The present paper describes the development of the two computer-tailored smoking cessation programs , their components and the design of the study . The study results reveal different working mechanisms of multiple tailored smoking cessation interventions and will help us to gain more insight into effective strategies to target different subgroups , especially smokers with a lower socio-economic status . Trial registration Dutch Trial Register Background Despite promising data in Western countries , there is a dearth of research into the efficacy of text messaging-based smoking cessation programs in other setting s , including the Middle East , where smoking prevalence rates are higher . Objective This paper reports cessation rates observed in SMS Turkey , a text messaging-based smoking cessation program for adult smokers in Ankara , Turkey . Methods This study was a small-scale , parallel-group r and omized controlled trial ( RCT ) conducted in Ankara , Turkey . Participants were adult daily smokers who were seriously thinking about quitting in the next 15 days and living in Ankara , Turkey . The text messaging intervention , SMS Turkey , provided 6 weeks of daily messages aim ed at giving participants skills to help them quit smoking . Messages were sent in an automated fashion , except 2 days and 7 days after the initial quit day . On days 2 and 7 , the research assistant manually assigned participants to content “ paths ” based on whether they were still not smoking or had relapsed . The control arm received a brochure that provided similar information about smoking cessation . The main outcome measure was self-reported 3-month sustained abstinence , verified by carbon monoxide ( CO ) readings . Neither participants nor research ers were blinded to arm assignment . Results The 151 participants were r and omly assigned to 1 of 2 groups : 76 to the SMS Turkey intervention group and 75 to the brochure control group . Using intention to treat , all 151 participants were included in analyses . Three-month cessation trends were not significantly higher in the intervention group : 11 % intervention vs 5 % control had quit ( χ2 1=1.4 , P=.24 ; R2=2.0 , 95 % CI 0.62 - 6.3 ) . When the sample was stratified by sex , female intervention participants ( 14 % , n=5 ) were significantly more likely to have quit at 3 months than female control participants ( 0 % , n=0 ; χ2 1=3.7 , P=.05 ) . Among light smokers ( ie , those smoking less than 20 cigarettes per day ) , intervention participants ( 17 % , n=5 ) also were significantly more likely to have quit compared to control participants ( 0 % , n=0 ; χ2 1=5.3 , P=.02 ) . We noted no difference in cessation rates for males or heavy smokers . Participants experienced significant technology problems during the study . Some participants received duplicate text messages at least once during the trial ; others failed to receive some program messages . Neither receiving duplicate messages ( χ2 1=0.12 , P=.73 ) , or missing 5 or more program messages ( χ2 1=0.75 , P=.39 ) negatively affected quitting rates . Conclusions Although the study was not powered to detect statistically significant differences , as the primary aim was to provide estimates of effect size that could be used to better inform a power analysis for a larger trial , findings provide optimism that SMS Turkey may be able to affect quitting rates in environments with high smoking prevalence , such as Ankara , Turkey . The SMS Turkey software program did not work as well as it did 2 years previous . The system will need to be up date d to maintain software compatibility with ongoing technology evolution . Trial Registration Clinical trials.gov NCT00912795 http:// clinical trials.gov/ct2/show/NCT00912795 ( Archived by WebCite at http://www.webcitation.org/6Ch1cIA8l ) OBJECTIVE To test whether adding mobile application coaching and patient/provider web portals to community primary care compared with st and ard diabetes management would reduce glycated hemoglobin levels in patients with type 2 diabetes . RESEARCH DESIGN AND METHODS A cluster-r and omized clinical trial , the Mobile Diabetes Intervention Study , r and omly assigned 26 primary care practice s to one of three stepped treatment groups or a control group ( usual care ) . A total of 163 patients were enrolled and included in analysis . The primary outcome was change in glycated hemoglobin levels over a 1-year treatment period . Secondary outcomes were changes in patient-reported diabetes symptoms , diabetes distress , depression , and other clinical ( blood pressure ) and laboratory ( lipid ) values . Maximal treatment was a mobile- and web-based self-management patient coaching system and provider decision support . Patients received automated , real-time educational and behavioral messaging in response to individually analyzed blood glucose values , diabetes medications , and lifestyle behaviors communicated by mobile phone . Providers received quarterly reports summarizing patient ’s glycemic control , diabetes medication management , lifestyle behaviors , and evidence -based treatment options . RESULTS The mean declines in glycated hemoglobin were 1.9 % in the maximal treatment group and 0.7 % in the usual care group , a difference of 1.2 % ( P = 0.001 ) over 12 months . Appreciable differences were not observed between groups for patient-reported diabetes distress , depression , diabetes symptoms , or blood pressure and lipid levels ( all P > 0.05 ) . CONCLUSIONS The combination of behavioral mobile coaching with blood glucose data , lifestyle behaviors , and patient self-management data individually analyzed and presented with evidence -based guidelines to providers substantially reduced glycated hemoglobin levels over 1 year Background Tobacco use is responsible for the death of about 1 in 10 individuals worldwide . Mindfulness training has shown preliminary efficacy as a behavioral treatment for smoking cessation . Recent advances in mobile health suggest advantages to smartphone-based smoking cessation treatment including smartphone-based mindfulness training . This study evaluates the efficacy of a smartphone app-based mindfulness training program for improving smoking cessation rates at 6-months follow-up . Methods / Design A two-group parallel-r and omized clinical trial with allocation concealment will be conducted . Group assignment will be concealed from study research ers through to follow-up . The study will be conducted by smartphone and online . Daily smokers who are interested in quitting smoking and own a smartphone ( n = 140 ) will be recruited through study advertisements posted online . After completion of a baseline survey , participants will be allocated r and omly to the control or intervention group . Participants in both groups will receive a 22-day smartphone-based treatment program for smoking . Participants in the intervention group will receive mobile mindfulness training plus experience sampling . Participants in the control group will receive experience sampling-only . The primary outcome measure will be one-week point prevalence abstinence from smoking ( at 6-months follow-up ) assessed using carbon monoxide breath monitoring , which will be vali date d through smartphone-based video chat . Discussion This is the first intervention study to evaluate smartphone-based delivery of mindfulness training for smoking cessation . Such an intervention may provide treatment in-h and , in real-world context s , to help individuals quit smoking . Trial registration Clinical trials.gov NCT02134509 . Registered 7 May 2014 Background Happy Ending ( HE ) is an intense 1-year smoking cessation program delivered via the Internet and cell phone . HE consists of more than 400 contacts by email , Web pages , interactive voice response , and short message service technology . HE includes a craving helpline and a relapse prevention system , providing just-in-time therapy . All the components of the program are fully automated . Objective The objectives were to describe the rationale for the design of HE , to assess the 12-month efficacy of HE in a sample of smokers willing to attempt to quit without the use of nicotine replacement therapy , and to explore the potential effect of HE on coping planning and self-efficacy ( prior to quitting ) and whether coping planning and self-efficacy mediate treatment effect . Methods A two-arm r and omized controlled trial was used . Subjects were recruited via Internet advertisements and r and omly assigned to condition . Inclusion criteria were willingness to quit on a prescribed day without using nicotine replacement and being aged 18 years or older . The intervention group received HE , and the control group received a 44-page self-help booklet . Abstinence was defined as “ not even a puff of smoke , for the last seven days ” and was assessed by means of Internet surveys or telephone interviews 1 , 3 , 6 , and 12 months postcessation . The main outcome was repeated point abstinence ( ie , abstinence at all four time points ) . Coping planning and self-efficacy were measured at baseline and at the end of the preparation phase ( ie , after 2 weeks of treatment , but prior to cessation day ) . Results A total of 290 participants received either the HE intervention ( n=144 ) or the control booklet ( n=146 ) . Using intent-to-treat analysis , participants in the intervention group reported clinical ly and statistically significantly higher repeated point abstinence rates than control participants ( 20 % versus 7 % , odds ratio [ OR ] = 3.43 , 95 % CI = 1.60 - 7.34 , P = .002 ) . Although no differences were observed at baseline , by the end of the preparation phase , significantly higher levels of coping planning ( t 261 = 3.07 , P = .002 ) and precessation self-efficacy ( t 261 = 2.63 , P = .01 ) were observed in the intervention group compared with the control group . However , neither coping planning nor self-efficacy mediated long-term treatment effect . For point abstinence 1 month after quitting , however , coping planning and self-efficacy showed a partial mediation of the treatment effect . Conclusions This 12-month trial documents a long-term treatment effect of a fully automated smoking cessation intervention without the use of nicotine replacement therapy . The study adds to the promise of using digital media in supporting behavior change The aim was to compare the effectiveness of untailored text messages for smoking cessation to tailored text messages delivered at a higher frequency . From February 2007 to August 2009 , 2030 users of an internet-based smoking cessation program with optional text message support aged 15 - 25 years were consecutively r and omized to versions of the program that offered either tailored or untailored text messages . Thirty-day point abstinence from smoking was measured self-reportedly at 12-months follow-up . Response rates were 36.3 % and 38.1 % in the tailored and untailored group , respectively . We analyzed the entire study population , as well as those opting for text messages ( n = 1619 ) . In intention-to-treat analysis with multiple imputation of missing data , the odds ratio for 30-day point abstinence was 1.28 ( 95 % CI 0.91 - 2.08 ) for the tailored compared with untailored messages . When restricting the analysis to those who had chosen to receive text messages , the corresponding odds ratio was 1.45 ( 95 % CI 1.01 - 2.08 ) . The higher long-term quit rates in the group receiving the tailored text messages compared with untailored text messages in the restricted analysis indicated that tailoring and higher frequency of text messages increases quit rates among young smokers Background Recruitment is a major challenge for trials but there is little evidence regarding interventions to increase trial recruitment . We report three controlled trials of interventions to increase recruitment to the Txt2stop trial . Purpose To evaluate : Trial 1 . The impact on registration s of a text message regarding an online registration facility ; Trial 2 . The impact on r and omizations of sending £ 5 with a covering letter to those eligible to join the trial ; Trial 3 . The impact on r and omizations of text messages containing quotes from existing participants . Methods Single blind controlled trials with allocation concealment . Interventions : Trial 1 : A text message regarding our new online registration facility ; Trial 2 : A letter with £ 5 enclosed ; Trial 3 : A series of four text messages containing quotes from participants . The control group in each trial received st and ard Txt2stop procedures . Results Trial 1 : 3.6 % ( 17/470 ) of the intervention group and 1.1 % ( 5/467 ) of the control group registered for the trial , risk difference 2.5 % ( 95 % CI 0.6—4.5 ) . 0 % ( 0/ 470 ) of the intervention group and 0.2 % ( 1/467 ) of the control group registered successfully online , risk difference —0.2 ( 95 % CI —0.6—0.2 ) ; Trial 2 : 4.5 % ( 11/246 ) of the intervention group and 0.4 % ( 1/245 ) of the control group were r and omized into the Txt2stop trial , risk difference 4.0 % ( 95 % CI 1.4—6.7 ) ; Trial 3 : 3.5 % ( 14/405 ) of the intervention group and 0 % ( 0/406 ) of the control group were r and omized into the Txt2stop trial , risk difference 3.5 ( 95 % CI 1.7—5.2 ) . Limitations There were no baseline data available for trial 1 . Allocation of participant IDs in trials 2 and 3 were systematic . Conclusion Sending a text message about an online registration facility increased registration s to Txt2stop , but did not increase online registration s. Sending a £ 5 reimbursement for participants ’ time and sending text messages containing quotes from existing participants increased r and omizations into the Txt2stop trial . Clinical Trials 2010 ; 7 : 265—273 . AIMS To assess the long-term efficacy of a fully automated digital multi-media smoking cessation intervention . DESIGN Two-arm r and omized control trial ( RCT ) . Setting World Wide Web ( WWW ) study based in Norway . PARTICIPANTS Subjects ( n = 396 ) were recruited via internet advertisements and assigned r and omly to conditions . Inclusion criteria were willingness to quit smoking and being aged 18 years or older . INTERVENTION The treatment group received the internet- and cell-phone-based Happy Ending intervention . The intervention programme lasted 54 weeks and consisted of more than 400 contacts by e-mail , web-pages , interactive voice response ( IVR ) and short message service ( SMS ) technology . The control group received a self-help booklet . Additionally , both groups were offered free nicotine replacement therapy ( NRT ) . MEASUREMENTS Abstinence was defined as ' not even a puff of smoke , for the last 7 days ' , and assessed by means of internet surveys or telephone interviews . The main outcome was repeated point abstinence at 1 , 3 , 6 and 12 months following cessation . FINDINGS Participants in the treatment group reported clinical ly and statistically significantly higher repeated point abstinence rates than control participants [ 22.3 % versus 13.1 % ; odds ratio ( OR ) = 1.91 , 95 % confidence interval ( CI ) : 1.12 - 3.26 , P = 0.02 ; intent-to-treat ) . Improved adherence to NRT and a higher level of post-cessation self-efficacy were observed in the treatment group compared with the control group . CONCLUSIONS As the first RCT documenting the long-term treatment effects of such an intervention , this study adds to the promise of digital media in supporting behaviour change Background Mobile technology offers the potential to deliver health-related interventions to individuals who would not otherwise present for in-person treatment . Text messaging ( short message service , SMS ) , being the most ubiquitous form of mobile communication , is a promising method for reaching the most individuals . Objective The goal of the present study was to evaluate the feasibility and preliminary efficacy of a smoking cessation intervention program delivered through text messaging . Methods Adult participants ( N=60 , age range 18 - 52 years ) took part in a single individual smoking cessation counseling session , and were then r and omly assigned to receive either daily non-smoking related text messages ( control condition ) or the TXT-2-Quit ( TXT ) intervention . TXT consisted of automated smoking cessation messages tailored to individual ’s stage of smoking cessation , specialized messages provided on-dem and based on user requests for additional support , and a peer-to-peer social support network . Generalized estimating equation analysis was used to assess the primary outcome ( 7-day point-prevalence abstinence ) using a 2 ( treatment groups) × 3 ( time points ) repeated measures design across three time points : 8 weeks , 3 months , and 6 months . Results Smoking cessation results showed an overall significant group difference in 7-day point prevalence abstinence across all follow-up time points . Individuals given the TXT intervention , with higher odds of 7-day point prevalence abstinence for the TXT group compared to the Mojo group ( OR=4.52 , 95 % CI=1.24 , 16.53 ) . However , individual comparisons at each time point did not show significant between-group differences , likely due to reduced statistical power . Intervention feasibility was greatly improved by switching from traditional face-to-face recruitment methods ( 4.7 % yield ) to an online/remote strategy ( 41.7 % yield ) . Conclusions Although this study was design ed to develop and provide initial testing of the TXT-2-Quit system , these initial findings provide promising evidence that a text-based intervention can be successfully implemented with a diverse group of adult smokers . Trial Registration Clinical Trials.gov : NCT01166464 ; http:// clinical trials.gov/ct2/show/NCT01166464 ( Archived by WebCite at http://www.webcitation.org/6IOE8XdE0 ) Background Preliminary findings suggest that Web-based interventions may be effective in achieving significant smoking cessation . To date , very few findings are available for primary care patients , and especially for the involvement of general practitioners . Objective Our goal was to examine the short-term effectiveness of a fully automated Web-based coaching program in combination with accompanied telephone counseling in smoking cessation in a primary care setting . Methods The study was an unblinded cluster-r and omized trial with an observation period of 12 weeks . Individuals recruited by general practitioners r and omized to the intervention group participated in a Web-based coaching program based on education , motivation , exercise guidance , daily short message service ( SMS ) reminding , weekly feedback through Internet , and active monitoring by general practitioners . All components of the program are fully automated . Participants in the control group received usual care and advice from their practitioner without the Web-based coaching program . The main outcome was the biochemically confirmed smoking status after 12 weeks . Results We recruited 168 participants ( 86 intervention group , 82 control group ) into the study . For 51 participants from the intervention group and 70 participants from the control group , follow-up data were available both at baseline and 12 weeks . Very few patients ( 9.8 % , 5/51 ) from the intervention group and from the control group ( 8.6 % , 6/70 ) successfully managed smoking cessation ( OR 0.86 , 95 % CI 0.25 - 3.0 ; P=.816 ) . Similar results were found within the intent-to-treat analysis : 5.8 % ( 5/86 ) of the intervention group and 7.3 % ( 6/82 ) of the control group ( OR 1.28 , 95 % CI 0.38 - 4.36 ; P=.694 ) . The number of smoked cigarettes per day decreased on average by 9.3 in the intervention group and by 6.6 in the control group ( 2.7 mean difference ; 95 % CI -5.33 to -0.58 ; P=.045 ) . After adjustment for the baseline value , age , gender , and height , this significance decreases ( mean difference 2.2 ; 95 % CI -4.7 to 0.3 ; P=.080 ) . Conclusions This trial did not show that the tested Web-based intervention was effective for achieving smoking cessation compared to usual care . The limited statistical power and the high drop-out rate may have reduced the study ’s ability to detect significant differences between the groups . Further r and omized controlled trials are needed in larger population s and to investigate the long-term outcome . Trial Registration German Register for Clinical Trials , registration number DRKS00003067 ; http://drks-neu.uniklinik-freiburg.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL _ ID = DRKS00003067 ( Archived by WebCite at http://www.webcitation.org/6Sff1YZpx ) Background Smoking tobacco is one of the most preventable causes of illness and death . Web-based tailored smoking cessation interventions have shown to be effective . Although these interventions have the potential to reach a large number of smokers , they often face high attrition rates , especially among lower educated smokers . A possible reason for the high attrition rates in the latter group is that computer-tailored smoking cessation interventions may not be attractive enough as they are mainly text-based . Video-based messages might be more effective in attracting attention and stimulating comprehension in people with a lower educational level and could therefore reduce attrition rates . Objective The objective of the present study was to investigate whether differences exist in message-processing mechanisms ( attention , comprehension , self-reference , appreciation , processing ) and future adherence ( intention to visit/use the website again , recommend the website to others ) , according to delivery strategy ( video or text based messages ) and educational level , to a Dutch computer-tailored smoking cessation program . Methods Smokers who were motivated to quit within the following 6 months and who were aged over 16 were included in the program . Participants were r and omly assigned to one of two conditions ( video/text CT ) . The sample was stratified into 2 categories : lower and higher educated participants . In total , 139 participants completed the first session of the web-based tailored intervention and were subsequently asked to fill out a question naire assessing message-processing mechanisms and future adherence . ANOVAs and regression analyses were conducted to investigate the differences in message-processing mechanisms and future adherence with regard to delivery strategy and education . Results No interaction effects were found between delivery strategy ( video vs text ) and educational level on message-processing mechanisms and future adherence . Delivery strategy had no effect on future adherence and processing mechanisms . However , in both groups results indicated that lower educated participants showed higher attention ( F 1,138=3.97 ; P=.05 ) and processing levels ( F 1,138=4.58 ; P=.04 ) . Results revealed also that lower educated participants were more inclined to visit the computer-tailored intervention website again ( F 1,138=4.43 ; P=.04 ) . Conclusions Computer-tailored programs have the potential to positively influence lower educated groups as they might be more involved in the computer-tailored intervention than higher educated smokers . Longitudinal studies with a larger sample are needed to gain more insight into the role of delivery strategy in tailored information and to investigate whether the intention to visit the intervention website again results in the ultimate goal of behavior change . Trial Registration Netherl and s Trial Register ( NTR3102 ) 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 BACKGROUND Cigarette smoking among persons living with HIV ( PLWH ) is a pressing public health concern , and efforts to evaluate cessation treatments are needed . The purpose of the present study was to assess potential mechanisms of a cell phone-delivered intervention for HIV-positive smokers . METHODS Data from 350 PLWH enrolled in a r and omized smoking cessation treatment trial were utilized . Participants were r and omized to either usual care ( UC ) or a cell phone intervention ( CPI ) group . The independent variable of interest was treatment group membership , while the dependent variable of interest was smoking abstinence at a 3-month follow-up . The hypothesized treatment mechanisms were depression , anxiety , social support , quit motivation and self-efficacy change scores . RESULTS Abstinence rates in the UC and CPI groups were 4.7 % ( 8 of 172 ) and 15.7 % ( 28 of 178 ) , respectively . The CPI group ( vs. UC ) experienced a larger decline in depression between baseline and the 3-month follow-up , and a decline in anxiety . Self-efficacy increased for the CPI group and declined for the UC group . Quit motivation and social support change scores did not differ by treatment group . Only self-efficacy met the predefined criteria for mediation . The effect of the cell phone intervention on smoking abstinence through change in self-efficacy was statistically significant ( p<0.001 ) and accounted for 17 % of the total effect of the intervention on abstinence . CONCLUSIONS The findings further emphasize the important mechanistic function of self-efficacy in promoting smoking cessation for PLWH . Additional efforts are required to disentangle the relationships between emotional , distress motivation , and efficacious smoking cessation treatment Background Tobacco smoking prevalence continues to be high , particularly among adolescents and young adults with lower educational levels , and is therefore a serious public health problem . Tobacco smoking and problem drinking often co-occur and relapses after successful smoking cessation are often associated with alcohol use . This study aims at testing the efficacy of an integrated smoking cessation and alcohol intervention by comparing it to a smoking cessation only intervention for young people , delivered via the Internet and mobile phone . Methods / Design A two-arm cluster-r and omised controlled trial with one follow-up assessment after 6 months will be conducted . Participants in the integrated intervention group will : ( 1 ) receive individually tailored web-based feedback on their drinking behaviour based on age and gender norms , ( 2 ) receive individually tailored mobile phone text messages to promote drinking within low-risk limits over a 3-month period , ( 3 ) receive individually tailored mobile phone text messages to support smoking cessation for 3 months , and ( 4 ) be offered the option of registering for a more intensive program that provides strategies for smoking cessation centred around a self-defined quit date . Participants in the smoking cessation only intervention group will only receive components ( 3 ) and ( 4 ) . Study participants will be 1350 students who smoke tobacco daily/occasionally , from vocational schools in Switzerl and . Main outcome criteria are 7-day point prevalence smoking abstinence and cigarette consumption assessed at the 6-month follow up . Discussion This is the first study testing a fully automated intervention for smoking cessation that simultaneously addresses alcohol use and interrelations between tobacco and alcohol use . The integrated intervention can be easily implemented in various setting s and could be used with large groups of young people in a cost-effective way . Trial registration Current Controlled Trials IS RCT N02427446 ( date of registration : 08th September , 2014 ) Objectives : To determine the effectiveness of a mobile phone text messaging smoking cessation programme . Design : R and omised controlled trial Setting : New Zeal and Participants : 1705 smokers from throughout New Zeal and who wanted to quit , were aged over 15 years , and owned a mobile phone were r and omised to an intervention group that received regular , personalised text messages providing smoking cessation advice , support , and distraction , or to a control group . All participants received a free month of text messaging ; starting for the intervention group on their quit day to assist with quitting , and starting for the control group at six months to encourage follow up . Follow up data were available for 1624 ( 95 % ) at six weeks and 1265 ( 74 % ) at six months . Main outcome measures : The main trial outcome was current non-smoking ( that is , not smoking in the past week ) six weeks after r and omisation . Secondary outcomes included current non-smoking at 12 and 26 weeks . Results : More participants had quit at six weeks in the intervention compared to the control group : 239 ( 28 % ) v 109 ( 13 % ) , relative risk 2.20 ( 95 % confidence interval 1.79 to 2.70 ) , p < 0.0001 . This treatment effect was consistent across subgroups defined by age , sex , income level , or geographic location ( p homogeneity > 0.2 ) . The relative risk estimates were similar in sensitivity analyses adjusting for missing data and salivary cotinine verification tests . Reported quit rates remained high at six months , but there was some uncertainty about between group differences because of incomplete follow up . Conclusions : This programme offers potential for a new way to help young smokers to quit , being affordable , personalised , age appropriate , and not location dependent . Future research should test these findings in different setting s , and provide further assessment of long term quit rates 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 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 Primary care is an important setting for smoking cessation interventions . There is evidence for the effectiveness of tailored interventions for smoking cessation , and text messaging interventions for smoking cessation show promise . The intervention to be evaluated in this trial consists of two components : ( 1 ) a web-based program design ed to be used by a practice nurse or other smoking cessation advisor ( SCA ) ; the program generates a cessation advice report that is highly tailored to relevant characteristics of the smoker ; and ( 2 ) a three-month programme of automated tailored text messages sent to the smoker ’s mobile phone . The objectives of the trial are to assess the acceptability and feasibility of the intervention and to estimate the short-term effectiveness of the intervention in increasing the quit rate compared with usual care alone . Methods / design The design is a two parallel group r and omised controlled trial ( RCT ) . 600 smokers who want to quit will be recruited in up to 30 general practice s in the East of Engl and . During a consultation with an SCA , they will be individually r and omised by computer program to usual care ( Control ) or to usual care plus the iQuit system ( Intervention ) . At the four-week follow-up appointment , the SCA will record smoking status and measure carbon monoxide level . There will be two further follow-ups , at eight weeks and six months from r and omisation date , by postal question naire sent from and returned to the study centre or by telephone interview conducted by a research interviewer . The primary outcome will be self-reported abstinence for at least two weeks at eight weeks . A sample size of 300 per group would give 80 % power to detect an increase in quit rate from 20 % to 30 % ( alpha = 0.05 , 2-sided test ) . The main analyses of quit rates will be conducted on an intention-to-treat basis , making the usual assumption that participants lost to follow up are smoking . Discussion This trial will focus on acceptability , feasibility and short-term effectiveness . The findings will be used to refine the intervention and to inform the decision to proceed to a pragmatic trial to estimate longer-term effectiveness and cost-effectiveness . Trial registration IS RCT Background Tobacco consumption is the most preventable cause of morbidity-mortality in the world . One aspect of smoking cessation that merits in-depth study is the use of an application design ed for smartphones ( app ) , as a supportive element that could assist younger smokers in their efforts to quit . To assess the efficacy of an intervention that includes the assistance of a smoking cessation smartphone application targeted to young people aged 18 to 30 years who are motivated to stop smoking . Methods / design Cluster r and omised clinical trial . Setting : Primary Health Care centres ( PHCCs ) in Catalonia . Analyses based on intention to treat . Participants : motivated smokers of 10 or more cigarettes per day , aged 18 to 30 years , consulting PHCCs for any reason and who provide written informed consent to participate in the trial . Intervention group will receive a 6-month smoking cessation programme that implements recommendations of a Clinical Practice Guideline , complemented with a smartphone app design ed specifically for this programme . Control group will receive the usual care . The outcome measure will be abstinence at 12 months confirmed by exhaled-air carbon monoxide concentration of at least 10 parts per million at each control test . Discussion To our knowledge this is the first r and omised controlled trial of a programme comparing the efficacy of usual care with a smoking cessation intervention involving a mobile app . If effective , the modality could offer a universal public health management approach to this common health concern . Trial registration Background Tobacco use remains the number one cause of preventable chronic disease and death in developed countries worldwide . In North America , smoking rates are highest among young adults . Despite that the majority of young adult smokers indicate wanting to quit , smoking rates among this age demographic have yet to decline . Helping young adults quit smoking continues to be a public health priority . Digital mobile technology presents a promising medium for reaching this population with smoking cessation interventions , especially because young adults are the heaviest users of this technology . Objective The primary aim of this trial is to determine the effectiveness of an evidence -informed mobile phone app for smoking cessation , Crush the Crave , on reducing smoking prevalence among young adult smokers . Methods A parallel r and omized controlled trial ( RCT ) with two arms will be conducted in Canada to evaluate Crush the Crave . In total , 1354 young adult smokers ( 19 to 29 years old ) will be r and omized to receive the evidence -informed mobile phone app , Crush the Crave , or an evidence -based self-help guide known as “ On the Road to Quitting ” ( control ) for a period of 6 months . The primary outcome measure is a 30-day point prevalence of abstinence at the 6-month follow-up . Secondary outcomes include a 7-day point prevalence of abstinence , number of quit attempts , reduction in consumption of cigarettes , self-efficacy , satisfaction , app utilization metrics , and use of smoking cessation services . A cost-effectiveness analysis is included . Results This trial is currently open for recruitment . The anticipated completion date for the study is April 2016 . Conclusions This r and omized controlled trial will provide the evidence to move forward on decision making regarding the inclusion of technology-based mobile phone interventions as part of existing smoking cessation efforts made by health care providers . Evidence from the trial will also inform the development of future apps , provide a deeper underst and ing of the factors that drive change in smoking behavior using an app , and improve the design of cessation apps . This trial is among the first to assess the effect of a comprehensive and evidence -informed mHealth smoking cessation app on a large sample of young adult smokers . Strengths of the trial include the high- quality research design and in-depth assessment of the implementation of the intervention . If effective , the trial has the potential to demonstrate that including mHealth technology as a population -based intervention strategy can cost-effectively reach a greater proportion of the population and help young adult smokers to quit . Trial Registration Clinical Trials.gov NCT01983150 ; http:// clinical trials.gov/ct2/show/NCT01983150 ( Archived by WebCite at http://www.webcitation.org/6VGyc0W0i ) Globally , tobacco smoke is the leading cause of preventable deaths . Smoking cessation counselling services are widely available in Canada . In British Columbia , our government-funded smoking cessation service offers counselling via phone , text , or email . In this study , we sought to determine whether age , gender , or motivation to quit affect a patient 's choice of service modality . We included all adults ≥ 18 years who had used tobacco within 30 days prior to their Emergency Department ( ED ) visit and who chose to receive phone , text , or email counselling services from November 2011–February 2013 at Vancouver General Hospital as part of a r and omized-controlled trial ( Clinical Trials.gov , NCT0145437 ) . A one-way ANOVA was used to compare the mean age of patients in each group . Chi-squared tests of independence were used to determine if gender or motivation to quit were associated with modality selection . In total , 368 patients were included . The average age was 41.7 years and 67 % were female . In our study , 44 % chose phone , 17 % chose text , and 40 % chose email services . The average age for patients preferring text services ( mean = 33.6 years ) was significantly lower than both the email ( mean = 41.3 years ) and phone ( mean = 45.1 years ) groups ( p < 0.001 ) . Gender and motivation to quit were not associated with service modality choice . Over 80 % of ED smokers who accepted a referral to counselling services chose the phone or email modality . The lesser chosen text modality was more popular with younger patients . With further research , smoking cessation counselling services can refine their programs to meet the needs of the population they serve Background Smoking prevalence remains high , particularly among adolescents and young adults with lower educational levels , posing a serious public health problem . There is limited evidence of effective smoking cessation interventions in this population . Objective To test the efficacy of an individually tailored , fully automated text messaging ( short message service , SMS)–based intervention for smoking cessation in young people . Methods A 2-arm cluster r and omized controlled trial , using school class as the r and omization unit , was conducted to test the efficacy of the SMS text messaging intervention compared to an assessment -only control group . Students who smoked were proactively recruited via online screening in vocational school classes . Text messages , tailored to demographic and smoking-related variables , were sent to the participants of the intervention group at least 3 times per week over a period of 3 months . A follow-up assessment was performed 6 months after study inclusion . The primary outcome measure was 7-day smoking abstinence . Secondary outcomes were 4-week smoking abstinence , cigarette consumption , stage of change , and attempts to quit smoking . We used regression models controlling for baseline differences between the study groups to test the efficacy of the intervention . Both complete-case analyses ( CCA ) and intention-to-treat analyses ( ITT ) were performed . Subgroup analyses were conducted for occasional and daily smokers . Results A total of 2638 students in 178 vocational school classes in Switzerl and participated in the online screening . Overall , 1012 persons met the inclusion criteria for study participation , and 755 persons ( 74.6 % ) participated in the study ( intervention : n=372 ; control : n=383 ) . Of the 372 program participants , 9 ( 2.4 % ) unsubscribed from the program during the intervention period . Six-month follow-up data were obtained for 559 study participants ( 74.0 % ) . The 7-day smoking abstinence rate at follow-up was 12.5 % in the intervention group and 9.6 % in the control group ( ITT : P=.92 ) . No differences between the study groups were observed in 4-week point prevalence abstinence rates . The decrease in the mean number of cigarettes smoked per day from baseline to follow-up was higher in the intervention group than in the control group ( ITT : P=.002 ) . No differences between the groups were observed in stage of change ( ITT : P=.82 ) and quit attempts ( ITT : P=.38 ) . The subgroup analyses revealed lower cigarette consumption in both occasional and daily smokers in the intervention group compared to the control group . Occasional smokers in the intervention group made more attempts to quit smoking than occasional smokers in the control group . Conclusions This study demonstrated the potential of an SMS text message – based intervention to reach a high proportion of young smokers with low education levels . The intervention did not have statistically significant short-term effects on smoking cessation ; however , it result ed in statistically significant lower cigarette consumption . Additionally , it result ed in statistically significant more attempts to quit smoking in occasional smokers . Trial Registration International St and ard R and omized Controlled Trial Number ( IS RCT N ) : 19739792 ; http://www.controlled-trials.com/IS RCT N19739792 ( Archived by WebCite at http://webcitation.org/6IGETTHmr ) Background Despite a significant decrease in smoking prevalence over the past ten years , cigarette smoking still represents the leading cause of preventable morbidity and mortality in the United States . Moreover , smoking prevalence is significantly higher among those with low levels of education and those living at , or below , the poverty level . These groups tend to be confronted with significant barriers to utilizing more traditional smoking cessation intervention approaches . The purpose of the study , Project ACTION ( Adult smoking Cessation Treatment through Innovative Outreach to Neighborhoods ) , is to utilize a mobile clinic model , a network of community sites ( i.e. , community centers and churches ) and an interactive mobile messaging system to reach and deliver smoking cessation treatment to underserved , low-income communities . Methods / Design We are using a group-r and omized design , with the community site as the sampling unit , to compare the efficacy of three smoking cessation interventions : 1 ) St and ard Care - brief advice to quit smoking , nicotine replacement therapy ( NRT ) , and self-help material s ; 2 ) Enhanced Care - st and ard care components plus a cell phone-delivered text/graphical messaging component ; and 3 ) Intensive Care - enhanced care components plus a series of 11 cell phone-delivered proactive counseling sessions . An economic evaluation will also be performed to evaluate the relative cost effectiveness of the three treatment approaches . We will recruit 756 participants ( 252 participants in each of the 3 intervention groups ) . At the time of r and omization , participants complete a baseline assessment , consisting of smoking history , socio-demographic , and psychosocial variables . Monthly cell phone assessment s are conducted for 6 months-post enrollment , and a final 12-month follow-up is conducted at the original neighborhood site of enrollment . We will perform mixed-model logistic regression to compare the efficacy of the three smoking cessation intervention treatment groups . Discussion It is hypothesized that the intensive care approach will most successfully address the needs of the target population and result in the highest smoking cessation rates . In addition to increasing cessation rates , the intervention offers several features ( including neighborhood outreach and use of mHealth technology ) that are likely to reduce treatment barriers while enhancing participant engagement and retention to treatment . Trial registration This r and omized controlled trial is registered with clinical trials.gov registration number NCT00948129 Introduction In a previous study exploring the feasibility of a smoking cessation application ( app ) , we found that about 77 % of the respondents from three countries were ready to quit in the next 30 days without significant differences between countries in terms of age , operating system and number of quitting attempts . However , the efficacy of smartphone apps for smoking cessation has not yet been established . This study tests the efficacy of a smartphone smoking cessation decision-aid app compared with an app that contains only smoking cessation information . Methods and analysis This is an automated double-blind , r and omised controlled trial of a smoking cessation app that contains the eligibility requirements and baseline question naire and will r and omise the participants into one of the two subapps ( the intervention and the control ) . Participants will be recruited directly from the Apple app stores in Australia , Singapore , the UK and the USA . Daily smokers aged 18 and above will be r and omised into one of the subapps after completing the baseline question naire . Abstinence rates will be measured at 10 days , 1 month , 3 months and 6 months , with the 1-month follow-up abstinence rate as the primary outcome . Logistic regression mixed models will be used to analyse the primary outcome . Ethics and dissemination This study was approved by the University of Sydney 's Human Ethics Committee . The results of the trial will be published in peer- review ed journals according to the CONSORT statement . Trial registration number Australian New Zeal and Clinical Trial RegistryACTRN12613000833763 The aim was to better underst and structural factors associated with uptake of automated tailored interventions for smoking cessation . In a prospect i ve r and omized controlled trial with interventions only offered , not m and ated , participants were r and omized based on the following : web-based expert system ( QuitCoach ) ; text messaging program ( onQ ) ; both as an integrated package ; the choice of using either or both ; or a control condition informed of a static website ( not considered here ) . Participants were 3530 smokers or recent quitters recruited from two sources ; those seeking smoking cessation information , mostly recruited over the phone , and a cold-contacted group recruited from an Internet panel . More participants ( 60.1 % ) initially accepted the intervention they had been offered than used it ( 42.5 % ) . Uptake of each intervention differed substantially by both recruitment source and modality ( phone or web ) . onQ was a little more popular overall , especially in the information seeker sample . Highest overall intervention uptake occurred in the choice condition . A web-based intervention is most attractive if the offer to use is made by web , whereas a phone-based intervention is more likely to be used if the offer is made over the phone . Providing automated interventions on multiple platforms allows for maximal choice and greatest overall use of some form of help Background A wide range of effective smoking cessation interventions have been developed to help smokers to quit . Smoking rates remain high , especially among people with a lower level of education . Multiple tailoring adapted to the individual ’s readiness to quit and the use of visual messaging may increase smoking cessation . Objective The results of video and text computer tailoring were compared with the results of a control condition . Main effects and differential effects for subgroups with different educational levels and different levels of readiness to quit were assessed . Methods During a blind r and omized controlled trial , smokers willing to quit within 6 months were assigned to a video computer tailoring group with video messages ( n=670 ) , a text computer tailoring group with text messages ( n=708 ) , or to a control condition with short generic text advice ( n=721 ) . After 6 months , effects on 7-day point prevalence abstinence and prolonged abstinence were assessed using logistic regression analyses . Analyses were conducted in 2 sample s : ( 1 ) respondents ( as r and omly assigned ) who filled in the baseline question naire and completed the first session of the program , and ( 2 ) a sub sample of sample 1 , excluding respondents who did not adhere to at least one further intervention session . In primary analyses , we used a negative scenario in which respondents lost to follow-up were classified as smokers . Complete case analysis and multiple imputation analyses were considered as secondary analyses . Results In sample 1 , the negative scenario analyses revealed that video computer tailoring was more effective in increasing 7-day point prevalence abstinence than the control condition ( OR 1.45 , 95 % CI 1.09 - 1.94 , P=.01 ) . Video computer tailoring also result ed in significantly higher prolonged abstinence rates than controls among smokers with a low ( ready to quit within 4 - 6 months ) readiness to quit ( OR 5.13 , 95 % CI 1.76 - 14.92 , P=.003 ) . Analyses of sample 2 showed similar results , although text computer tailoring was also more effective than control in realizing 7-day point prevalence abstinence . No differential effects were found for level of education . Complete case analyses and multiple imputation yielded similar results . Conclusions In all analyses , video computer tailoring was effective in realizing smoking cessation . Furthermore , video computer tailoring was especially successful for smokers with a low readiness to quit smoking . Text computer tailoring was only effective for sample 2 . Results suggest that video-based messages with personalized feedback adapted to the smoker ’s motivation to quit might be effective in increasing abstinence rates for smokers with diverse educational levels . Trial Registration Netherl and s Trial Register : NTR3102 ; http://www.trialregister.nl/trialreg/admin/ rct view.asp?TC=3102 ( Archived by WebCite at http://www.webcitation.org/6NS8xhzUV ) Background Particularly in groups of adolescents with lower educational level the smoking prevalence is still high and constitutes a serious public health problem . There is limited evidence of effective smoking cessation interventions in this group . Individualised text messaging ( SMS ) based interventions are promising to support smoking cessation and could be provided to adolescents irrespective of their motivation to quit . The aim of the current paper is to outline the study protocol of a trial testing the efficacy of an SMS based intervention for smoking cessation in apprentices . Methods / Design A two-arm cluster-r and omised controlled trial will be conducted to test the efficacy of an SMS intervention for smoking cessation in adolescents and young adults compared to an assessment only control group . A total of 910 daily or occasional ( ≥ 4 cigarettes in the preceding month and ≥ 1 cigarette in the preceding week ) smoking apprentices will be proactively recruited in vocational school classes and , using school class as a r and omisation unit , r and omly assigned to an intervention group ( n = 455 ) receiving the SMS based intervention or an assessment only control group ( n = 455 ) . Individualised text messages taking into account demographic data and the individuals ' smoking behaviours will be sent to the participants of the intervention group over a period of 3 months . Participants will receive two text messages promoting smoking cessation per week . Program participants who intend to quit smoking have the opportunity to use a more intensive SMS program to prepare for their quit day and to prevent a subsequent relapse . The primary outcome measure will be the proportion of participants with 7-day point prevalence smoking abstinence assessed at 6-months follow-up . The research assistants conducting the baseline and the follow-up assessment s will be blinded regarding group assignment . Discussion It is expected that the program offers an effective and inexpensive way to promote smoking cessation among adolescents and young adults including those with lower educational level and independent of their motivation to quit . Trial registration numberIS RCT N : IS RCT Background Cardiac rehabilitation ( CR ) is a secondary prevention program that offers education and support to assist patients with coronary heart disease ( CHD ) make lifestyle changes . Despite the benefits of CR , attendance at centre-based sessions remains low . Mobile technology ( mHealth ) has potential to reach more patients by delivering CR directly to mobile phones , thus providing an alternative to centre-based CR . The aim of this trial is to evaluate if a mHealth comprehensive CR program can improve adherence to healthy lifestyle behaviours ( for example , physically active , fruit and vegetable intake , not smoking , low alcohol consumption ) over and above usual CR services in New Zeal and adults diagnosed with CHD . Methods / design A two-arm , parallel , r and omised controlled trial will be conducted at two Auckl and hospitals in New Zeal and . One hundred twenty participants will be r and omised to receive a 24-week evidence - and theory-based personalised text message program and access to a supporting website in addition to usual CR care or usual CR care alone ( control ) . The primary outcome is the proportion of participants adhering to healthy behaviours at 6 months , measured using a composite health behaviour score . Secondary outcomes include overall cardiovascular disease risk , body composition , illness perceptions , self-efficacy , hospital anxiety/depression and medication adherence . Discussion This study is one of the first to examine an mHealth-delivered comprehensive CR program . Strengths of the trial include quality research design and in-depth description of the intervention to aid replication . If effective , the trial has potential to augment st and ard CR practice s and to be used as a model for other disease prevention or self-management programs . Trial registryAustralian New Zeal and Clinical Trials Registry : Background Tobacco use remains the leading cause of premature morbidity and mortality in the United States . Young adults are less successful at quitting , use cessation treatment less often than smokers of other ages , and can be a challenge to retain in treatment . Social media , integrated into the lives of many young adults , represents a promising strategy to deliver evidence -based smoking cessation treatment to a large , diverse audience . The goal of this trial is to test the efficacy of a stage-based smoking cessation intervention on Facebook for young adults age 18 to 25 on smoking abstinence , reduction in cigarettes smoked , and thoughts about smoking abstinence . Methods / Design This is a r and omized controlled trial . Young adult smokers throughout the United States are recruited online and r and omized to either the 3 month Tobacco Status Project intervention on Facebook or a referral to a smoking cessation website . The intervention consists of assignment to a secret Facebook group tailored to readiness to quit smoking ( precontemplation , contemplation , preparation ) , daily Facebook contacts tailored to readiness to quit smoking , weekly live counseling sessions , and for those in preparation , weekly Cognitive Behavioral Therapy counseling sessions on Facebook . Primary outcome measure is biochemically-verified 7-day point prevalence abstinence from smoking at posttreatment ( 3 months ) , 6 , and 12 months . Secondary outcome measures are reduction of 50 % or more in cigarettes smoked , 24 h quit attempts , and commitment to abstinence at each time point . A secondary aim is to test , within the TSP condition , the effect of a monetary incentive at increasing engagement in the intervention . Discussion This r and omized controlled trial is testing a novel Facebook intervention for treating young adults ’ tobacco use . If efficacious , the social media intervention could be disseminated widely and exp and ed to address additional health risks . Trial registration Clinical Trials.gov : NCT02207036 , May 13 , 2014 BACKGROUND People living with human immunodeficiency virus (HIV)/AIDS ( PLWHA ) have a substantially higher prevalence of cigarette smoking compared to the general population . In addition , PLWHA are particularly susceptible to the adverse health effects of smoking . Our primary objective was to design and test the efficacy over 12 months of a smoking cessation intervention targeting PLWHA . METHODS Participants were enrolled from an urban HIV clinic with a multiethnic and economically disadvantaged patient population . Participants received smoking cessation treatment either through usual care ( UC ) or counseling delivered by a cell phone intervention ( CPI ) . The 7-day point prevalence abstinence was evaluated at 3 , 6 , and 12 months using logistic regression and generalized linear mixed models . RESULTS We r and omized 474 HIV-positive smokers to either the UC or CPI group . When evaluating the overall treatment effect ( 7-day abstinence outcomes from 3- , 6- , and 12-month follow-ups ) , participants in the CPI group were 2.41 times ( P = .049 ) more likely to demonstrate abstinence compared to the UC group . The treatment effect was strongest at the 3-month follow-up ( odds ratio = 4.3 , P < .001 ) , but diminished at 6 and 12 months ( P > .05 ) . CONCLUSIONS Cell phone-delivered smoking cessation treatment has a positive impact on abstinence rates compared to a usual care approach . Future research should focus on strategies for sustaining the treatment effect in the long term The main objective of this paper is to present a new program that facilitates the management of people who want to quit smoking , implemented through an e-treatment software called S-PC ( Smoker Patient Control ) . S-PC is a web-based application that manages groups of patients , provides a bidirectional communication through mobile text messages and e-mails between patients and clinicians and offers advice and control to keep track of the patients and their status . A total of 229 patients were enrolled in the study , r and omly divided into two groups , although some variables were tested to ensure that there were no significant differences between the groups that could have an impact on the outcome of the treatment . There were no significant differences between the two groups regarding the ratio/number of males/females , tobacco dependence , co-oximetry , average cigarette consumption , current age and age when smoking started . The first group was made up of 104 patients ( 45.4 % of the total ) and followed a treatment that incorporated the S-PC tool , while the second one had 125 patients without the S-PC tool . S-PC was evaluated for its effectiveness at assisting the patients to give up smoking , and its effect on clinician time management . 74 % of the S-PC group completed the treatment without relapses and remained abstinent three months after the completion of the treatment , underst and ing abstinence as being continuous ( with no relapses allowed and co-oximetry below 1 ppm ) from the day of stopping . In contrast only 45.6 % of the No S-PC group completed the treatment without relapses and remained abstinent three months after completion of the treatment . The rate of admittance to the program has doubled in one year and patients went from having to wait for 3 months to be immediately admitted into the program . This therapeutic e-health program aims at maximizing the number of patients that a professional can effectively help to quit smoking . In addition , the system also detects patients who are not progressing appropriately , allowing the professional to improve their treatment parameters dynamically BACKGROUND There is a dual need for ( 1 ) innovative theory-based smartphone applications for smoking cessation and ( 2 ) controlled trials to evaluate their efficacy . Accordingly , this study tested the feasibility , acceptability , preliminary efficacy , and mechanism of behavioral change of an innovative smartphone-delivered acceptance and commitment therapy ( ACT ) application for smoking cessation vs. an application following US Clinical Practice Guidelines . METHOD Adult participants were recruited nationally into the double-blind r and omized controlled pilot trial ( n=196 ) that compared smartphone-delivered ACT for smoking cessation application ( SmartQuit ) with the National Cancer Institute 's application for smoking cessation ( QuitGuide ) . RESULTS We recruited 196 participants in two months . SmartQuit participants opened their application an average of 37.2 times , as compared to 15.2 times for QuitGuide participants ( p<0001 ) . The overall quit rates were 13 % in SmartQuit vs. 8 % in QuitGuide ( OR=2.7 ; 95 % CI=0.8 - 10.3 ) . Consistent with ACT 's theory of change , among those scoring low ( below the median ) on acceptance of cravings at baseline ( n=88 ) , the quit rates were 15 % in SmartQuit vs. 8 % in QuitGuide ( OR=2.9 ; 95 % CI=0.6 - 20.7 ) . CONCLUSIONS ACT is feasible to deliver by smartphone application and shows higher engagement and promising quit rates compared to an application that follows US Clinical Practice Guidelines . As results were limited by the pilot design ( e.g. , small sample ) , a full-scale efficacy trial is now needed Abstract Background : Currently , there are over 400 smoking cessation smartphone apps available , downloaded an estimated 780,000 times per month . No prior studies have examined how individuals engage with specific features of cessation apps and whether use of these features is associated with quitting . Objectives : Using data from a pilot trial of a novel smoking cessation app , we examined : ( i ) the 10 most-used app features , and ( ii ) prospect i ve associations between feature usage and quitting . Methods : Participants ( n = 76 ) were from the experimental arm of a r and omized , controlled pilot trial of an app for smoking cessation called “ SmartQuit , ” which includes elements of both Acceptance and Commitment Therapy ( ACT ) and traditional cognitive behavioral therapy ( CBT ) . Utilization data were automatically tracked during the 8-week treatment phase . Thirty-day point prevalence smoking abstinence was assessed at 60-day follow-up . Results : The most-used features – quit plan , tracking , progress , and sharing – were mostly CBT . Only two of the 10 most-used features were prospect ively associated with quitting : viewing the quit plan ( p = 0.03 ) and tracking practice of letting urges pass ( p = 0.03 ) . Tracking ACT skill practice was used by fewer participants ( n = 43 ) but was associated with cessation ( p = 0.01 ) . Conclusions : In this exploratory analysis without control for multiple comparisons , viewing a quit plan ( CBT ) as well as tracking practice of letting urges pass ( ACT ) were both appealing to app users and associated with successful quitting . Aside from these features , there was little overlap between a feature ’s popularity and its prospect i ve association with quitting . Tests of causal associations between feature usage and smoking cessation are now needed INTRODUCTION Poly-tobacco use is defined as cigarette and other tobacco consumption with either product used daily or nondaily . While concurrent use of different types of tobacco has been documented within the general population , less is known about poly-tobacco use among HIV-positive smokers and its impact on smoking cessation efforts . OBJECTIVE To characterize the profile of poly-tobacco users ( PTU ) in a sample of HIV-positive smokers participating in a cessation program . METHODS The study sample consisted of 474 HIV-positive smokers enrolled in a 2-group r and omized controlled trial of cigarette smoking cessation comparing a cell phone-based intervention to usual care . Prevalence was determined , and risk factors for poly-tobacco use were evaluated using logistic regression . RESULTS In this cohort of HIV-positive cigarette smokers , 21.6 % of participants were PTU , with cigars ( 73.4 % ) the most common tobacco product consumed . Among PTU , 73.5 % used other form(s ) of tobacco some days , and 26.5 % use them every day . Perceived discrimination and unemployment were significantly associated with poly-tobacco use after adjusting for other demographic , behavioral , and psychosocial factors . Analysis showed that participants in the cell phone group ( vs. usual care ) were more likely to report 24-hr abstinence , both among monocigarette users ( 16.6 % vs. 6.3 % , p < .001 ) and PTU ( 18.5 % vs. 0 % , p < .001 ) . CONCLUSION Poly-tobacco use prevalence among adult HIV-positive smokers was considerably higher than in the general population . Special attention must be placed on concurrent use of cigarettes and cigars among HIV-positive smokers . Because PTU are a unique population less likely to succeed in brief smoking cessation interventions , effective cessation programs are needed Aims To estimate the short-term effectiveness , feasibility and acceptability of a smoking cessation intervention ( the iQuit system ) that consists of tailored printed and Short Message Service ( SMS ) text message self-help delivered as an adjunct to cessation support in primary care to inform the design of a definitive trial . Design A stratified two parallel-group r and omized controlled trial comparing usual care ( control ) with usual care plus the iQuit system ( intervention ) , delivered by primary care nurses/healthcare assistants who were blinded to the allocation sequence . Setting Thirty-two general practice ( GP ) surgeries in Engl and , UK . Participants A total of 602 smokers initiating smoking cessation support from their local GP surgery were r and omized ( control n = 303 , intervention n = 299 ) . Measurements Primary outcome was self-reported 2-week point prevalence abstinence at 8 weeks follow-up . Secondary smoking outcomes and feasibility and acceptability measures were collected at 4 weeks after quit date , 8 weeks and 6 months follow-up . Findings There were no significant between-group differences in the primary outcome [ control 40.3 % , iQuit 45.2 % ; odds ratio ( OR ) = 1.22 , 95 % confidence interval ( CI ) = 0.88–1.69 ] or in secondary short-term smoking outcomes . Six-month prolonged abstinence was significantly higher in the iQuit arm ( control 8.9 % , iQuit 15.1 % ; OR = 1.81 , 95 % CI = 1.09–3.01 ) . iQuit support took on average 7.7 minutes ( st and ard deviation = 4.0 ) to deliver and 18.9 % ( 95 % CI = 14.8–23.7 % ) of intervention participants discontinued the text message support during the programme . Conclusions Tailored printed and text message self-help delivered alongside routine smoking cessation support in primary care does not significantly increase short-term abstinence , but may increase long-term abstinence and demonstrated feasibility and acceptability compared with routine cessation support alone BACKGROUND Text messaging programs on mobile phones have shown some promise in helping people quit smoking . Text2Quit is an automated , personalized , interactive mobile health program that sends text messages to offer advice , support , and reminders about quitting smoking . PURPOSE To evaluate the effect of Text2Quit on biochemically confirmed repeated point prevalence abstinence in the context of an RCT conducted in the U.S. METHODS Participants ( n=503 ) were recruited on the Internet and r and omized to receive Text2Quit or self-help material . Between 2011 and 2013 , participants were surveyed at baseline and at 1 , 3 , and 6 months post-enrollment to assess smoking status . Saliva was collected from participants who reported not smoking in the past 7 days at the 6-month follow-up . An intent to treat analysis was used , and those lost to follow-up were categorized as smokers . All analyses were completed in 2013 . RESULTS Biochemically confirmed repeated point prevalence abstinence favored the intervention group , with 11.1 % abstinent compared to 5.0 % of the control group ( relative risk=2.22 , 95 % CI=1.16 , 4.26 , p<0.05 ) . Similarly , self-reported repeated point prevalence abstinence was higher in the intervention group ( 19.9 % ) than in the control group ( 10.0 % ) ( p<0.01 ) . Effects were found to be uniform across the analyzed demographic subgroups , although suggestive of a larger effect for non-whites than whites . CONCLUSIONS These results provide initial support for the relative efficacy of the Text2Quit program AIMS To determine whether a smoking cessation service using mobile phone text messaging is as effective for Maori as non-Maori . METHODS A single-blind r and omised controlled trial was undertaken with recruitment targeted to maximise the participation of young Maori . The intervention included regular , personalised text messages providing smoking cessation advice , support , and distraction . Maori text messages related to Maori language , support messages ( in Maori and English ) and information on Maori traditions . Text messaging was free for 1 month . After 6 weeks , the number of messages reduced from 5 per day to 3 per week until the 26-week follow-up . RESULTS Participants included 355 Maori and 1350 non-Maori . Maori in the intervention group were more likely to report quitting ( no smoking in the past week ) at 6 weeks ( 26.1 % ) than those in the control group ( 11.2 % ) RR 2.34 , 95 % CI : 1.44 - 3.79 . There was no significant difference between the RR for Maori and that for non-Maori ( RR : 2.16 , 95%CI : 1.72 - 2.71 ) . CONCLUSIONS A mobile phone-based cessation programme was successful in recruiting young Maori , and was shown to be as effective for Maori as non-Maori at increasing short-term self-reported quit rates . This shows clear potential as a new public health initiative INTRODUCTION To address the lack of smoking cessation programs available to young adults , Stop My Smoking ( SMS ) USA , a text messaging-based smoking cessation program , was developed and pilot tested . METHODS This was a two-arm r and omized controlled trial with adaptive r and omization ( arms were balanced by sex and smoking level [ heavy vs. light ] ) , conducted nationally in the United States . One hundred sixty-four 18- to 25-year-old daily smokers who were seriously thinking about quitting in the next 30 days were r and omized to either ( a ) the 6-week SMS USA intervention ( n = 101 ) or ( b ) an attention-matched control group aim ed at improving sleep and physical activity ( n = 63 ) . The main outcome measure was 3-month continuous abstinence , verified by a significant other . Participants but not research ers were blinded to study arm allocation . RESULTS Based upon intent-to-treat analyses , intervention participants ( 39 % ) were significantly more likely than control participants ( 21 % ) to have quit at 4 weeks postquit ( adjusted odds ratio [ aOR ] = 3.33 , 95 % confidence interval [ CI ] : 1.48 , 7.45 ) . Findings were not sustained at 3 months postquit , although rates in the SMS USA group were favored ( 40 % vs. 30 % , respectively ; aOR = 1.59 , 95 % CI : 0.78 , 3.21 ) . Subsequent analyses suggested that among intervention participants , SMS USA might be more influential for youth not currently enrolled in a higher education ( p = .06 ) . CONCLUSIONS Consistent with pilot studies , the sample was underpowered . Data suggest , however , that the SMS USA program affects smoking cessation rates at 4 weeks postquit . More research is needed before conclusions can be made about long-term impact . Identifying profiles of users for whom the program may be particularly beneficial also will be important ABSTRACT Little is known about the relative , additive , and interactive effects of different population -based treatments for smoking cessation . The goal of this study was to evaluate the main and interactive effects of five different smoking interventions . Using the multiphase optimization strategy ( MOST ) , 1,034 smokers who entered a Web site for smokers ( smokefree.gov ) were r and omly assigned to the “ on ” and “ off ” conditions of five smoking cessation interventions : the National Cancer Institute ’s ( NCI ) Web site ( www.smokefree.gov vs a “ lite ” Web site ) , telephone quitline counseling ( vs none ) , a smoking cessation brochure ( vs a lite brochure ) , motivational e-mail messages ( vs none ) , and mini-lozenge nicotine replacement therapy ( NRT vs none ) . Analyses showed that the NCI Web site and NRT both increased abstinence ; however , the former increased abstinence significantly only when it was not used with the e-mail messaging intervention ( messaging decreased Web site use ) . The other interventions showed little evidence of effectiveness . There was evidence that mailed nicotine mini-lozenges and the NCI Web site ( www.smokefree.gov ) provide benefit as population -based smoking interventions INTRODUCTION The objective of this study was to test the feasibility and acceptance of an intervention using text messaging ( short message service [ SMS ] ) for continuous individual support of smoking cessation in young adults . Additionally , the optimal feedback intensity was investigated , and short-term efficacy of the intervention was explored . METHODS In a cafeteria of the University of Greifswald , 575 visitors were screened for smoking status and usage of text messaging . From these , 194 persons who fulfilled the inclusion criteria of daily smoking and weekly usage of SMS were invited for participation in an SMS-based intervention . From these , 174 ( 90 % ) consented to participate . The participants were r and omly allocated to one of three study groups : ( a ) control condition without intervention , ( b ) intervention with one weekly SMS feedback ( 1SMS ) , or ( c ) intervention with three weekly SMS feedbacks ( 3SMS ) . In study groups ( b ) and ( c ) , individualized SMS feedbacks were sent to the participants weekly , based on data from the baseline assessment and a weekly SMS assessment of the stages of change according to the transtheoretical model . Program use and acceptance were compared between the two intervention groups differing in support intensity . An exploration of the short-term efficacy of the program was conducted by comparing the three study groups at the end of the 3-month intervention program on smoking variables . RESULTS The median number of replies to the weekly SMS assessment s was 12.5 in the 1SMS group and 13.0 in the 3SMS group ( not significant ) . The acceptance of the program did not differ between the intervention groups . At post assessment , no significant differences between the three study groups emerged on the examined smoking variables . DISCUSSION The high participation and retention rates suggest that SMS-based smoking cessation interventions are attractive for young adults . Support intensity did not affect the acceptance of the program . Longer follow-up periods and larger sample s are required to obtain conclusive results about the efficacy of this intervention approach BACKGROUND Text messaging has successfully supported smoking cessation . This study compares a mobile application with text messaging to support smoking cessation . MATERIAL S AND METHODS Young adult smokers 18 - 30 years old ( n = 102 ) participated in a r and omized pretest-posttest trial . Smokers received a smartphone application ( REQ-Mobile ) with short messages and interactive tools or a text messaging system ( onQ ) , managed by an expert system . Self-reported usability of REQ-Mobile and quitting behavior ( quit attempts , point-prevalence , 30-day point-prevalence , and continued abstinence ) were assessed in posttests . RESULTS Overall , 60 % of smokers used mobile services ( REQ-Mobile , 61 % , mean of 128.5 messages received ; onQ , 59 % , mean of 107.8 messages ) , and 75 % evaluated REQ-Mobile as user-friendly . A majority of smokers reported being abstinent at posttest ( 6 weeks , 53 % of completers ; 12 weeks , 66 % of completers [ 44 % of all cases ] ) . Also , 37 % ( 25%of all cases ) reported 30-day point-prevalence abstinence , and 32 % ( 22 % of all cases ) reported continuous abstinence at 12 weeks . OnQ produced more abstinence ( p<0.05 ) than REQ-Mobile . Use of both services predicted increased 30-day abstinence at 12 weeks ( used , 47 % ; not used , 20 % ; p = 0.03 ) . CONCLUSIONS REQ-Mobile was feasible for delivering cessation support but appeared to not move smokers to quit as quickly as text messaging . Text messaging may work better because it is simple , well known , and delivered to a primary inbox . These advantages may disappear as smokers become more experienced with new h and sets . Mobile phones may be promising delivery platforms for cessation services using either smartphone applications or text messaging OBJECTIVE To study whether demographic and smoking-related characteristics are associated with participation ( reach ) in a smoking cessation trial and subsequent use ( uptake ) of two specific smoking interventions ( Internet-based program and proactive telephone counseling ) . METHODS We used data from a four-arm r and omized smoking cessation trial ( 2011 ) . Participants ( n=1,809 ) were recruited among 9,924 smokers who previously participated in two health surveys in Denmark ( 2007 - 2008 and 2010 ) . Interventions were as follows : ( 1 ) an Internet-based smoking cessation program , ( 2 ) proactive telephone counseling , ( 3 ) reactive telephone counseling and ( 4 ) a self-help booklet . RESULTS Reach ( defined as the proportion accepting to participate in the trial of those invited ) was highest among persons aged 40 - 59 years , women , heavy smokers and persons with long education . Among trial participants , uptake ( defined as any use of the specific intervention at 1-month follow-up ) was 69 % for the Internet-based program , 74 % and 9 % for proactive and reactive telephone counseling , respectively , and 84 % for the self-help booklet . Young age was associated with the uptake of the Internet-based program , and short education was associated with using proactive telephone counseling . CONCLUSIONS Internet-based interventions and proactive telephone counseling appeal to different age and educational groups . Further , offering similar intervention content by a proactive and a reactive approach can be associated with different intervention uptake Aim : To conduct a pilot r and omised controlled trial of mobile phone-based smoking cessation support intervention for the UK population . Design : R and omised controlled trial ( txt2stop ) . Setting : Community . Participants : 200 participants responding to radio , poster and leaflet-based promotions regarding the trial . Main outcome measures : The response rate for the outcome measures planned for the main trial . Participants ’ qualitative responses to open-ended questions about the intervention content . Secondary outcomes were the outcomes planned for the main trial including the point prevalence of self-reported smoking at 4 weeks and pooled effect estimate for the short-term results for the STOMP and txt2stop trials . Results : The response rate at 4 weeks was 96 % and at 6 months was 92 % . The results at 4 weeks show a doubling of self-reported quitting relative risk ( RR ) 2.08 ( 95 % CI 1.11 to 3.89 ) , 26 % vs 12 % . The pooled effect estimate combining txt2stop and a previous New Zeal and trial in the short term is RR 2.18 ( 95 % CI 1.79 to 2.65 ) . Conclusions : Mobile phone-based smoking cessation is an innovative means of delivering smoking cessation support , which doubles the self-reported quit rate in the short term . It could represent an important , but as yet largely unused , medium to deliver age-appropriate public health measures . The long-term effect of this mobile phone-based smoking cessation support will be established by a large r and omised controlled trial currently in recruitment AIMS To test the population impact of offering automated smoking cessation interventions via the internet and /or by mobile phone . DESIGN Pragmatic r and omized controlled trial with five conditions : offer of ( i ) minimal intervention control ; ( ii ) QuitCoach personalized tailored internet-delivered advice program ; ( iii ) onQ , an interactive automated text-messaging program ; ( iv ) an integration of both QuitCoach and onQ ; and ( v ) a choice of either alone or the combined program . SETTING Australia , via a mix of internet and telephone contacts . PARTICIPANTS A total of 3530 smokers or recent quitters recruited from those interested in quitting , and seeking self-help re sources ( n = 1335 ) or cold-contacted from internet panels ( n = 2195 ) . MEASUREMENTS The primary outcome was self-report of 6 months sustained abstinence at 7 months post-recruitment . FINDINGS Only 42.5 % of those offered one of the interventions took it up to a minimal level . The intervention groups combined had a non-significantly higher 6-month sustained abstinence rate than the control [ odds ratio ( OR ) = 1.48 ; 95 % confidence interval ( CI ) : 0.98 - 2.24 ] ( missing cases treated as smokers ) , with no differences between the interventions . Among those who used an intervention , there was a significant overall increase in abstinence ( OR = 1.95 ; CI : 1.04 - 3.67 ) , but not clearly so when analysing only cases with reported outcomes . Success rates were greater among those recruited after seeking information compared to those cold-contacted . CONCLUSIONS Smokers interested in quitting who were assigned r and omly to an offer of either the QuitCoach internet-based support program and /or the interactive automated text-messaging program had non-significantly greater odds of quitting for at least 6 months than those r and omized to an offer of a simple information website 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 INTRODUCTION Arguably , the greatest advantage of ecological momentary assessment ( EMA ) studies is that data are collected repeatedly in real-time and real-world situations , which reduces recall and situational biases and thus improves the accuracy and validity of the data collected . However , the validity of EMA data is contingent upon compliance rates . If participant characteristics are related to missing data , analyses should control for these factors , or they should be targeted in EMA training sessions . This study evaluates the impact of demographic and smoking-related participant characteristics on compliance to an EMA smoking study protocol . METHODS Prequit-day data were taken from the control arm of an ongoing r and omized controlled trial of a smoking-cessation program . After training , 119 participants were asked to carry a mobile device with them at all times for ~6 days and to log every cigarette they smoked in addition to completing r and omly scheduled assessment s. Different types of compliance were assessed : the percentage of completed r and om prompts ( signal-contingent compliance ) , the percentage of logged cigarettes per day compared to a timeline follow-back measure , and the correlation between logged cigarettes and a carbon monoxide assessment 2 hr later ( both event-contingent compliance ) . RESULTS Overall compliance rates were 78.48 % for event-contingent and 72.17 % for signal-contingent compliance . None of the demographic or smoking-related participant characteristics predicted signal-contingent compliance ; however , female participants showed higher event-contingent compliance than male participants , and Caucasian participants showed higher event-contingent compliance than non-Caucasian participants . CONCLUSIONS Compliance did not depend on smoking-related characteristics . EMA is a valid method for assessing smoking behavior in real-time and real-world setting PURPOSE : Efficient ways are needed to implement the secondary prevention ( SP ) of coronary heart disease . Because few studies have investigated Web-based SP programs , our aim was to determine the usefulness of a new Web-based telemonitoring system , connecting patients provided with self-measurement devices and care managers via mobile phone text messages , as a tool for SP . METHODS : A single-blind , r and omized controlled , clinical trial of 203 acute coronary syndrome ( ACS ) survivors , was conducted at a hospital in Madrid , Spain . All patients received lifestyle counseling and usual-care treatment . Patients in the telemonitoring group ( TMG ) sent , through mobile phones , weight , heart rate , and blood pressure ( BP ) weekly , and capillary plasma lipid profile and glucose monthly . A cardiologist accessed these data through a Web interface and sent recommendations via short message service . Main outcome measures were BP , body mass index ( BMI ) , smoking status , low-density lipoprotein-cholesterol ( LDL-c ) , and glycated hemoglobin A1c ( HbA1c ) . RESULTS : At 12-month followup , TMG patients were more likely ( RR = 1.4 ; 95 % CI = 1.1−1.7 ) to experience improvement in cardiovascular risk factors profile than control patients ( 69.6 % vs 50.5 % , P = .010 ) . More TMG patients achieved treatment goals for BP ( 62.1 % vs 42.9 % , P = .012 ) and HbA1c ( 86.4 % vs 54.2 % , P = .018 ) , with no differences in smoking cessation or LDL-c . Body mass index was significantly lower in TMG ( −0.77 kg/m2 vs + 0.29 kg/m2 , P = .005 ) . CONCLUSIONS : A telemonitoring program , via mobile phone messages , appears to be useful for improving the risk profile in ACS survivors and can be an effective tool for secondary prevention , especially for overweight patients |
13,865 | 29,694,674 | We conclude that there is moderate- quality evidence that regional anaesthesia may reduce the risk of developing PPP after three to 18 months after thoracotomy and three to 12 months after caesarean section .
There is low- quality evidence that regional anaesthesia may reduce the risk of developing PPP three to 12 months after breast cancer surgery .
On a caution ary note , we can not extend our conclusions to other surgical interventions or regional anaesthesia techniques , for example we can not conclude that paravertebral block reduces the risk of PPP after thoracotomy . | BACKGROUND Regional anaesthesia may reduce the rate of persistent postoperative pain ( PPP ) , a frequent and debilitating condition .
This review was originally published in 2012 and up date d in 2017 .
OBJECTIVES To compare local anaesthetics and regional anaesthesia versus conventional analgesia for the prevention of PPP beyond three months in adults and children undergoing elective surgery . | Background : Nonsteroidal antiinflammatory drugs are commonly used to treat postoperative and chronic pain . Animal studies suggest that these drugs act , in part , by blocking prostagl and in production in the spinal cord . The authors tested intrathecal ketorolac in patients with chronic or postoperative pain . Methods : After approval of the institutional review board and the Food and Drug Administration , three clinical studies were performed . First , 15 patients receiving chronic intrathecal morphine received 0.5–2.0 mg of intrathecal ketorolac . Second , 12 patients receiving chronic intrathecal morphine received , in a double-blinded , r and omized , cross-over design , intrathecal saline or 2.0 mg of ketorolac , with pain intensity as the primary outcome measure . Third , 30 patients undergoing total vaginal hysterectomy received , in a double-blinded , r and omized , controlled design , intrathecal saline or 2.0 mg of ketorolac , with bupivacaine with time to first morphine dose after surgery as the primary outcome measure . Results : Patients with chronic pain had many symptoms before intrathecal injection , without worsening of these symptoms from ketorolac . Pain intensity was reduced by intrathecal ketorolac , but this did not differ from placebo . In the first study , pain was reduced by intrathecal ketorolac in patients with high cerebrospinal fluid prostagl and in E2 concentrations but not in those with normal concentrations . Intrathecal ketorolac did not alter time to first morphine after surgery . Conclusions : Intrathecal ketorolac did not relieve chronic pain or extend anesthesia or analgesia from intrathecal bupivacaine administered at the beginning of surgery . Under the conditions of these studies , it seems that spinal cylcooxygenase activity does not contribute to chronic or postoperative pain The efficacy of bupivacaine instillation into preperitoneal space following laparoscopic herniorrhaphy for postoperative pain reduction is still in controversy . A r and omized controlled trial was conducted to determine the efficacy of bupivacaine instillation . The 40 patients , who had an inguinal hernia with no complication , unilateral or bilateral and recurrence or no recurrence after previous hernia repair , were r and omly assigned to receive bupivacaine ( n = 19 ) and normal saline ( n = 21 ) . The intervention or placebo was instilled into the preperitoneal space after total extraperitoneal laparoscopic herniorrhaphy . Pain intensity was assessed by using a visual analogue scale and verbal rating scale after the 1st , 2nd , 6th , 12th , and 24th hour postoperatively . For the bupivacaine and placebo group , mean pain scores were 3.5 versus 5.2 ( P = .059 ) , 2.9 versus 4.5 ( P = .117 ) , 2.1 versus 3.2 ( P = .101 ) , 1.5 versus 2.7 ( P = .145 ) , and 1.6 versus 2.0 ( P = .672 ) after the 1st , 2nd , 6th , 12th , and 24th hour , respectively . Complications developed in 4 patients in the bupivacaine group and 7 patients in the placebo group after 3 months follow-up time . There is no strong evidence to confirm that bupivacaine instillation into preperitoneal space after laparoscopic herniorrhaphy can reduce postoperative pain Objective : To characterize the beneficial effects of perioperative systemic lidocaine on length of hospital stay , gastrointestinal motility , and the inflammatory response after colorectal surgery . Summary Background Data : Surgery-induced stimulation of the inflammatory response plays a major role in the development of several postoperative disorders . Local anesthetics possess anti-inflammatory activity and are thought to positively affect patients ' outcome after surgery . This double-blinded , r and omized , and placebo-controlled trial aim ed to evaluate beneficial effects of systemic lidocaine and to provide insights into underlying mechanisms . Methods : Sixty patients undergoing colorectal surgery , not willing or unable to receive an epidural catheter , were r and omly assigned to lidocaine or placebo treatment . Before induction of general anesthesia , an intravenous lidocaine bolus ( 1.5 mg/kg ) was administered followed by a continuous lidocaine infusion ( 2 mg/min ) until 4 hours postoperatively . Length of hospital stay , gastrointestinal motility , and pain scores were recorded and plasma levels or expression of pro- and anti-inflammatory mediators determined . Results : Lidocaine significantly accelerated return of bowel function and shortened length of hospital stay by one day . No difference could be observed in daily pain ratings . Elevated plasma levels of IL-6 , IL-8 , complement C3a , and IL-1ra as well as expression of CD11b , l- and P-selectin , and platelet-leukocyte aggregates were significantly attenuated by systemic lidocaine . Conclusions : Perioperative intravenous lidocaine not only improved gastrointestinal motility but also shortened length of hospital stay significantly . Anti-inflammatory activity modulating the surgery-induced stress response may be one potential mechanism . Systemic lidocaine may thus provide a convenient and inexpensive approach to improve outcome for patients not suitable for epidural anesthesia OBJECTIVES To test the hypotheses that lidocaine 5 % patches decrease the severity of acute pain and incidence of persistent incisional pain after robotic cardiac valve surgery . DESIGN A r and omized , placebo-controlled , double-blind trial . SETTING Tertiary care academic medical center . SUBJECTS Patients having robotic cardiac valve surgery . METHODS Patients having robotic cardiac valve surgery were r and omly assigned to 5 % lidocaine patches or identical-appearing placebo patches . Patches were applied around each incision 12 hours/day until pain resolved , or for 6 months . Supplemental opioid was provided by patient-controlled analgesia or orally . Pain was initially evaluated with a Visual Analog Scale , and subsequently by telephone with a Verbal Response Scale and the Pain Disability Index ( our primary outcome ) after 1 week , 1 month , 3 months , and 6 months . Global Perceived Effect , a measure of patient satisfaction , was simultaneously recorded . Repeated- measures analysis of variance and generalized estimating equations were our primary statistical tools . RESULTS Acute pain scores and opioid use were low , as was the incidence of persistent pain . Lidocaine 5 % patches did not influence any measure of acute or persistent incisional pain . Estimated difference ( 95 % CI ) in mean Pain Disability Index for Lidocaine patch minus placebo was -2.5 ( 95 % CI -7.1 , 2.1 ) , P = 0.28 . CONCLUSIONS Lidocaine 5 % patches did not reduce acute or persistent pain in patients having robotic thoracic surgery , though pain scores were low in both treatment groups . Clinicians should choose alternative analgesic approaches in these patients Iliac crest bone graft remains the gold st and ard in achieving spinal arthrodesis , but chronic pain from graft harvest occurs in up to 39 % of patients . Studies have shown that a single administration of local anesthetic reduces short-term pain , but they have not adequately investigated possible longer-term benefits . The goal of this study was to determine whether local administration of bupivacaine after iliac crest bone graft harvesting reduces pain and improves patient-reported outcomes . In this prospect i ve , r and omized , controlled , and blinded clinical study , 40 patients were identified who underwent posterior spine fusion with iliac crest bone graft and were r and omized to receive either bupivacaine ( treatment group , n=20 ) or saline ( control group , n=20 ) at the iliac crest bone graft site . Pain at the harvest site was determined by a series of 12 visual and numeric pain scale assessment s. Short Form-12 mental and physical component scores , EuroQol-5D , and Oswestry Disability Index assessment s were made , along with determination of patient satisfaction and self-reported outcome of surgery . Baseline pain and outcome assessment s were statistically similar ( P>.05 ) . Average pain scores were lower for all 12 assessment s in the treatment group at mean follow-up of 5 weeks ( significant differences in 6 assessment s ) and 20 weeks ( significant differences in 2 assessment s ) . No significant differences were found in Short Form-12 and EuroQol-5D scores . For patients who underwent lumbar fusion , the treatment group had significantly improved Oswestry Disability Index scores ( mean±SD=10.8±7.1 vs 18.7±5.9 , P=.012 ) . Significantly more patients in the treatment group reported that surgery met all expectations ( 90 % vs 50 % , P=.016 ) . This study is the 1st to show that a single administration of bupivacaine at the iliac crest bone graft harvest site during posterior spine fusion surgery can result in improved outcomes and reduced pain far beyond the anesthetic duration of activity Summary Background . A r and omized prospect i ve double-blinded study was conducted in 100 patients suffering from mono- or bisegmental cervical retrospondylosis or disc herniation . Method . In group I , 50 patients were treated by injection of 10 ml Ropivacaine 7,5 % at the iliac crest bonegraft donorsite . Local anaesthetic ( LA ) was injected through the wound drainage after closure of the muscle fascia , the suction drainage was opened after closure of the skin . Group II was treated with 0,9 % saline . Operator and patient were blinded to the injected substance . Daily controls of pain intensity were made with the 10 cm visual analog scale from 0 ( no pain ) to 10 ( severe pain ) for 5 days . All patients were question ed regarding pain character and movement provoking pain . Additional pain medication was st and arized . Findings . Statistical analysis of mean pain intensity over the whole hospital stay showed a significant difference in pain intensity between the two groups ( p = 0,017 , Chi-Square test ) . The comparison between pain intensity with LA and without LA showed a gradual increase in statistical significance from day 1 to day 5 ( day 1 : p = 0,54 , not significant ; day 2 : p = 0,026 ; day 3 : p = 0,008 ; day 4 : p = 0,004 ; day 5 : p = 0,002).Interpretation . This data shows that intra-operative blockage of peripheral nociceptive structures results in decreased pain at later time points . We conclude that wound infiltration with 7,5 % Ropivacaine after bonegraft removal at the iliac crest is effective in reducing postoperative pain Surgical field infiltration with adrenaline is common practice for quality surgical field during cleft lip and palate repair in children . Intravascular absorption of adrenaline infiltration often leads to adverse haemodynamic responses . In this prospect i ve , double-blinded , r and omised study the haemodynamic effects , quality of surgical field and postoperative analgesia following surgical field infiltration with different concentrations of adrenaline with and without lignocaine were compared in 100 American Society of Anesthesiologists physical status I children aged six months to seven years undergoing cleft lip/palate surgery . A st and ard anaesthesia protocol was used and they were r and omised into four groups based on solution for infiltration : adrenaline 1:400000 ( group A ) , adrenaline 1:200,000 ( group B ) , lignocaine + adrenaline 1:400,000 ( group C ) and lignocaine + adrenaline 1:200,000 ( group D ) . Statistically significant tachycardia and hypertension occurred only in group B as compared to other groups ( P < 0.001 ) . The peak changes in heart rate and mean arterial pressure following infiltration occurred at 4.3±2.4 , 3.8±1.5 , 5.7±3.2 and 5.9±4.9 minutes in groups A , B , C and D respectively . Surgical field was comparable among all groups . Postoperative pain scores and rescue analgesic requirements were lesser in the groups where lignocaine was added to the infiltrating solution ( P < 0.05 ) . We found that 1:400000 or 1:200000 adrenaline with lignocaine 0.5 to 0.7 % is most suitable for infiltration in terms of stable haemodynamics , quality of surgical field and good postoperative analgesia in children Background : Postoperative pain mostly results from sensitization of afferent fibers at injury sites driving central sensitization . Recently , peripheral processes have gained attention as mechanisms of hyperalgesia , and prostagl and ins are among highly sensitizing agents . To date , perioperative administration of a single local dose of nonsteroidal antiinflammatory drugs has shown inconclusive efficacy . Rather than a single bolus , the current study evaluates the postoperative analgesic effect of diclofenac continuous intrawound infusion after elective cesarean delivery . Methods : Ninety-two parturients were r and omly allocated to receive a 48-h continuous intrawound infusion with 240 ml containing 300 mg diclofenac , 0.2 % ropivacaine , or saline . In the ropivacaine and saline groups , patients also received 75 mg intravenous diclofenac every 12 h for 48 h. Postoperative evaluation included intravenous morphine consumption by patient-controlled analgesia and visual analog pain scores . Punctate mechanical hyperalgesia surrounding the wound and presence of residual pain after 1 and 6 months were also assessed . Results : Continuous diclofenac infusion significantly reduced postoperative morphine consumption ( 18 mg ; 95 % confidence interval , 12.7–22.2 ) in comparison with saline infusion and systemic diclofenac ( 38 mg ; 95 % confidence interval , 28.8–43.7 ) ( P = 0.0009 ) without unique adverse effects . Postoperative analgesia produced by local diclofenac infusion was as effective as local ropivacaine infusion with systemic diclofenac . Conclusions : After elective cesarean delivery , continuous intrawound infusion of diclofenac demonstrates a greater opioid-sparing effect and better postoperative analgesia than the same dose administered as an intermittent intravenous bolus Background Inflammatory response is one of the key components of pain perception . Continuous infusion ( CWI ) of local anesthetics has been shown to be effective in controlling pain and reducing postoperative morphine consumption , but the effect of adding a potent anti-inflammatory drug ( such as a steroid ) has never been addressed . In our study , we want to investigate the effect of CWI with local anesthetic + methylprednisolone on acute and persistent pain , correlating clinical data with biomarkers of inflammation and genetic background . Methods / Design After approval by their institutional review board , three hospitals will enroll 120 patients undergoing major abdominal surgery in a r and omized , double-blind , phase III study . After a 24-h CWI of ropivacaine 0.2 % + methylprednisolone 1 mg/kg , patients will be r and omly assigned to receive either ropivacaine + steroid or placebo for the next 24 h. Then , patient-controlled CWI with only ropivacaine 0.2 % or placebo ( according to the group of r and omization ) is planned after 48 h up to 7 days ( bolus 10 ml , lock-out 1 h , maximum dose of 40 ml in 4 h ) . Morphine equivalent consumption up to 7 days will be analyzed , together with any catheter- or drug-related side effect . Persistent post-surgical pain ( PPSP ) incidence will also be investigated . Our primary endpoint is analgesic consumption in the first 7 days after surgery ; we will evaluate , as secondary endpoints , any catheter- or drug-related side effect , genotype/phenotype correlations between some polymorphisms and postoperative outcome in terms of morphine consumption , development of the inflammatory response , and incidence of PPSP . Finally , we will collect , in a subgroup of patients , wound exu date sample s by micro-dialysis , blood sample s , and urine sample s up to 72 h to investigate local and systemic inflammation and oxidative stress . Discussion This is a phase III trial to evaluate the safety and efficacy of wound infusion with steroid and local anesthetic . The study is aim ed also to evaluate how long this infusion has to be maintained in order to maximize effectiveness . Our data are intended to quantify the amount of ropivacaine and methylprednisolone needed by patients undergoing major abdominal surgery , to be stored in a new nanotechnology device for sustained pain treatment after surgery . We also aim to clarify the roles of inflammatory response , oxidative stress , and genetic background on postoperative and persistent pain after major abdominal surgery . Trial registration The trial was registered on Clinical Trials.gov ( NCT02002663 ) on 24 Oct. 2013 OBJECTIVE To compare the incidence in postsurgical persistent pain following breast cancer surgery in women receiving intravenous lidocaine compared to saline using vali date d pain instruments in accordance with the Initiative on Methods , Measurement , and Pain Assessment in Clinical Trials ( IMMPACT ) recommendations . METHODS The study was a r and omized , double-blinded , placebo-controlled , clinical trial . Subjects were r and omized into Group 1 ( 1.5 mg/kg bolus of intravenous lidocaine followed by a 2 mg/kg/hour infusion ) or Group 2 ( normal saline at the same bolus and infusion rate ) . Patients were evaluated at 3 and 6 months for the presence of chronic persistent postsurgical pain . RESULTS One hundred forty-eight patients were included in the study analysis . There were no differences in quality of recovery , pain burden , or opioid consumption between groups at 24 hours . Pain ( yes/no ) at 6 months attributed to surgery was reported in 29 % of Group 2 vs. 13 % of Group 1 patients ( P = 0.04 ) ; however , only 3 subjects ( 5 % ) in Group 1 and 2 subjects ( 3 % ) in Group 2 met IMMPACT criteria for persistent postoperative pain ( P = 0.99 ) . DISCUSSION Perioperative infusion of lidocaine has been reported to decrease the incidence of postsurgical pain at 3 and 6 months following mastectomy using dichotomous ( yes/no ) scoring . Although intravenous lidocaine reduced the reported incidence of pain at rest at 6 months , pain with activity , pain qualities , and the physical or emotional impact of the pain were unaffected . Future studies evaluating postsurgical persistent pain should adhere to the IMMPACT recommendations in order to more accurately describe the effect of an intervention on persistent pain Purpose A prospect i ve r and omized clinical trial was carried out to observe the analgesic efficacy of ropivacaine for postoperative pain following thoracolumbar spinal surgery . Methods Seventy-one patients with elective posterior thoracolumbar spinal surgery were r and omly divided into two groups . Local group received 0.33 % ropivacaine by pump through the wound , and intravenous group received flurbiprofen axetil , pentazocine and palonosetron via intravenous pump . We evaluated the level of pain , the incidence of adverse reactions at 2 , 4 , 6 , 12 , 24 , 36 and 48 h after operation , and the occurrence of chronic pain 3 months later . Results There were no significant differences in the pain level between the two groups . However , the incidence of nausea , vomiting and chronic pain was significantly lower in the local group . Conclusions Our results showed that local infusion of ropivacaine achieved similar analgesic effects to intravenous delivery of analgesic drugs , but significantly reduced incidence of nausea , vomiting and chronic pain Background Chronic inguinodynia ( groin pain ) is a common complication following open inguinal hernia repair or a Pfannenstiel incision but may also be experienced after other types of ( groin ) surgery . If conservative treatments are to no avail , tailored remedial surgery , including a neurectomy and /or a ( partial ) meshectomy , may be considered . Retrospective studies in patients with chronic inguinodynia suggested that spinal anaesthesia is superior compared to general anaesthesia in terms of pain relief following remedial operations . This r and omised controlled trial is design ed to study the effect of type of anaesthesia ( spinal or general ) on pain relief following remedial surgery for inguinodynia . Methods A total of 190 adult patients who suffer from unacceptable chronic ( more than 3 months ) inguinodynia , as subjectively judged by the patients themselves , are included . Only patients scheduled to undergo a neurectomy and /or a meshectomy by an open approach are considered for inclusion and r and omised to spinal or general anaesthesia . Patients are excluded if pain is attributable to abdominal causes or if any contraindications for either type of anaesthesia are present . Primary outcome is effect of type of anaesthesia on pain relief . Secondary outcomes include patient satisfaction , quality of life , use of analgesics and (in)direct medical costs . Patient follow-up period is one year . Discussion The first patient was included in January 2016 . The expected trial deadline is December 2019 . Potential effects are deemed related to the entire setting of type of anaesthesia . Since any setting is multifactorial , all of these factors may influence the outcome measures .This is the first large r and omised controlled trial comparing the two most frequently used anaesthetic techniques in remedial surgery for groin pain . There is a definite need for evidence -based strategies to optimise results of these types of surgery . Besides pain relief , other important patient-related outcome measures are assessed to include patient ’s perspectives on outcome .Trial registration The protocol ( protocol number NL54115.015.15 ) is approved by the Medical Ethics Committee of Máxima Medical Centre , Veldhoven , The Netherl and s. The study protocol was registered at www.trialregister.nl ( NTR registration number : 5586 ) on 15 January 2016 Purpose sThe purpose of this study was to compare the effects of lateral abdominal transversus abdominis plane block ( TAP block ) and iliohypogastric/ilioinguinal nerve block ( IHINB ) under ultrasound guidance for postoperative pain management of inguinal hernia repair . Secondary purpose s were to compare the complication rates of the two techniques and to examine the effects of TAP block and IHINB on chronic postoperative pain . Methods This was a prospect i ve r and omized controlled open-label study . After approval of the Research Ethics Board , a total of 90 patients were allocated to three groups of 30 by simple r and omized sampling as determined with a priori power analysis . Peripheral nerve blocks ( TAP block or IHINB ) were administered to patients following subarachnoid block according to their allocated group . Patient pain scores , additional analgesic requirements and complication rates were recorded periodically and compared . Results Pain scores were significantly lower in the study groups ( p < 0.001 , p < 0.001 , p < 0.001 , p = 0.002 , p < 0.001 , p < 0.001 for 1 , 2 , 4 , 6 , 24 , and 48 h and at 1 and 6 months , respectively ) . First pain declaration times were significantly longer in the study groups ( TAP block group [ GT ] 266.6 ± 119.7 min ; IHINB group [ GI ] 247.2 ± 128.7 min ; and control group [ GC ] 79.1 ± 66.2 min ; p < 0.001 ) . At 24 h , the numeric rating scale scores of GT were significantly lower than GI ( p = 0.048 ) . Additional analgesic requirements of GT and GI patients were found to be significantly lower than GC patients ( p = 0.001 , p < 0.001 , p = 0.006 , p = 0.002 , p = 0.001 , p < 0.001 for 1 , 2 , 4 , 6 , 24 , and 48 h , respectively ) . Conclusion We conclude that administration of TAP block or IHINB for patients undergoing inguinal herniorrhaphy reduces the intensity of both acute and chronic postoperative pain and additional analgesic requirements Background and Objectives The transversus abdominis plane ( TAP ) block is an established technique to manage post – cesarean delivery pain . Transversus abdominis plane blocks with a local anesthetic only offer no analgesic benefits compared with intrathecal morphine . Adjuvants to extend TAP block duration and possibly reduce wound hyperalgesia , known to be a risk factor for chronic pain , have not been studied . We hypothesized that a TAP block with clonidine will affect postsurgical wound hyperalgesia and improve pain outcomes . Methods Ninety women were r and omly assigned to receive 1 of 3 TAP blocks after cesarean delivery : saline ( placebo ) , bupivacaine ( BupTAP ) , or bupivacaine + clonidine ( CloTAP ) . The primary outcome was wound hyperalgesia index at 48 hours . Secondary outcomes included pain scores , analgesic consumption , and pain descriptors up to 12 months . Results Wound hyperalgesia index at 48 hours ( median [ 25th–75th percentiles ] ) was 1.07 ( 0.48–3.26 ) in the placebo group , 1.27 ( 0.59–2.95 ) in the BupTAP group , and 0.74 ( 0.09–2.25 ) in the CloTAP group ( P = 0.48 ) . Morphine request in the postanesthesia care unit was significantly higher in the placebo group compared with the other TAP groups ( P = 0.01 ) . Postoperative pain scores and requests for breakthrough medication at 48 hours ( 30 % in the placebo group , 24 % in the BupTAP group , and 12 % in the CloTAP group , P = 0.25 ) or chronic pain descriptors reported up to 12 months did not differ significantly among groups . Conclusions Adding clonidine to a TAP block with bupivacaine did not affect wound hyperalgesia index and it did not improve short-term or long-term pain scores in women undergoing elective cesarean delivery . Further studies are warranted to determine the benefits of antihyperalgesic adjuvants in TAP solutions for specific individuals at risk for chronic pain Background and objective To find out whether preoperative gabapentin use had a favourable effect on long-term postoperative pain in patients undergoing inguinal herniorrhaphy . Methods Sixty male patients – aged 20–40 years – who were scheduled for unilateral inguinal herniorrhaphy under spinal anaesthesia were included in this prospect i ve , r and omized , double-blind study . The patients were r and omly allocated to two groups : the gabapentin group ( n = 30 ) received single-dose 1.2 g oral gabapentin 1 h before surgery , and the placebo group received a placebo capsule instead . Spinal anaesthesia was performed with heavy bupivacaine , and all operations were performed by the same surgeon with the same technique . Postoperative analgesia was evaluated during sitting and lying with a visual analogue scale . Assessment of postoperative pain at 1 , 3 and 6 months was carried out with an 11-point numerical rating scale ; 0 indicating ‘ no pain ’ and 10 indicating ‘ worst pain imaginable ’ . Patients who had numerical rating scale scores of more than 0 were further evaluated with regard to the impact of pain on their daily activities . Results When compared with the placebo group , the gabapentin group displayed significantly lower visual analogue scale scores ( lying and sitting ) and total tramadol consumption at 8 , 12 , 16 , 20 and 24 h after surgery ( P < 0.05 ) and higher postoperative patient satisfaction scores ( P < 0.05 ) . Numerical rating scale scores at 1 , 3 and 6 months after surgery were lower in the gabapentin group than in the placebo group ( P < 0.05 ) . The number of patients whose daily activities were adversely affected by pain was smaller in the gabapentin group at the first month ; however , the two groups were found to be similar at 3 and 6 months . Conclusion We conclude that preoperative single-dose gabapentin decreases the intensity of acute postoperative pain , tramadol consumption and the incidence and intensity of pain in the first 6 months after inguinal herniorrhaphy BACKGROUND : The issue of postoperative pain after neurosurgery is controversial . It has been reported as mild to moderate and its treatment may be inadequate . Infiltration of the surgical site with local anesthetics has provided transient benefit after craniotomy , but its effect on chronic pain has not been evaluated . Accordingly , we design ed the present study to test the hypothesis that ropivacaine infiltration of the scalp reduces acute and persistent postoperative pain after intracranial tumor resection . METHODS : This was a prospect i ve , single-blinded study . Inclusion criteria were intracranial tumor resection , age ≥18 or ≤80 yr , and ability to underst and and use a visual analog scale ( VAS ) . Exclusion criteria were history of craniotomy , chronic drug abuse , and neurologic disorders . All eligible patients were r and omly included in Group I ( infiltration ) or C ( control ) . Postoperative analgesia was IV acetaminophen combined with nalbuphine . At the end of the surgery , Group I received an infiltration of the surgical site with 20 mL of ropivacaine 0.75 % . Acute pain was evaluated hourly by VAS during the first 24 h. The analgesic effect of ropivacaine was evaluated based on total consumption of nalbuphine and VAS scores . The incidence of persistent pain and neuropathic pain was assessed at the 2-mo postoperative evaluation . We used the Student ’s t-test to compare total nalbuphine consumption , repeated measures analysis of variance with post hoc Bonferroni t-test for VAS score and the Fisher ’s exact test for chronic and neuropathic pain . RESULTS : Fifty-two patients were enrolled , 25 in Group I and 27 in Group C. Demographic and intraoperative data were similar between groups . Group I showed a nonsignificant trend toward reduced nalbuphine consumption during the first postoperative day , 11.2 ± 9.2 mg vs 16.6 ± 11.0 mg for Group C ( mean ± sd , P = 0.054 ) . VAS scores were significantly higher in Group C. Two months after surgery , persistent pain was significantly lower in Group I , 2/24 ( 8 % ) vs 14/25 ( 56 % ) , P = 0.0003 . One patient ( 4.1 % ) in Group I versus six ( 25 % ) patients in Group C ( P = 0.04 ) experienced neuropathic pain . CONCLUSIONS : Because pain is moderate after intracranial tumor resection , there is limited interest in scalp infiltrations with ropivacaine in the acute postoperative period . Nevertheless , these infiltrations may be relevant for the rehabilitation of neurosurgical patients and their quality of life by limiting the development of persistent pain and particularly neuropathic pain BACKGROUND The contribution of the saphenous nerve in pain after major ankle surgery is unknown . The aim of this study was to evaluate its contribution in this context . METHODS Fifty patients were included in this prospect i ve , r and omized , controlled study . In all patients [ Group P ( popliteal ) and Group F ( popliteal+femoral ) ] , a popliteal catheter was placed before operation and ropivacaine 0.5 % ( 30 ml ) administered via this catheter ; major ankle surgery was then performed under spinal anaesthesia . In Group PF patients , an additional femoral catheter was sited before operation and ropivacaine 0.5 % ( 10 ml ) administered . Six hours after spinal anaesthesia ( defined as T(0 ) ) , a continuous infusion of ropivacaine 0.3 % ( 14 ml h(-1 ) ) was started through the popliteal catheter until T(24 ) . Then , the concentration was reduced to 0.2 % until T(48 ) . Patients in Group PF received continuous ropivacaine 0.2 % ( 5 ml h(-1 ) ) through the femoral catheter from T(0 ) to T(48 ) . I.V. morphine patient-controlled analgesia was used as a rescue analgesia . Pain at rest , pain with movement , adverse effects , and i.v . morphine consumption were assessed . Pain at rest and on movement was evaluated 6 months after operation . RESULTS Pain at rest was comparable in the two groups . In Group PF , patients had significantly reduced pain during movement in the postoperative period ( P=0.01 ) and 6 months after operation ( P=0.03 ) . Morphine consumption was significantly reduced in Group PF at T(0)-T(24 ) and T(24)-T(48 ) ( P=0.01 ) . Adverse effects were comparable in both groups . CONCLUSIONS The addition of continuous femoral catheter infusion of ropivacaine to a continuous popliteal catheter infusion improved postoperative analgesia during movement after major ankle surgery . This effect was still present 6 months after surgery Background : Ketamine potentiates intravenous or epidural morphine analgesia . The authors hypothesized that very-low-dose ketamine infusion reduces acute and long-term postthoracotomy pain . Methods : Forty-nine patients scheduled to undergo open thoracotomy were r and omly assigned to receive one of two anesthesia regimens : continuous epidural infusion of ropivacaine and morphine , along with intravenous infusion of ketamine ( 0.05 mg · kg−1 · h−1 [ approximately 3 mg/h ] , ketamine group , n = 24 ) or placebo ( saline , control group , n = 25 ) . Epidural analgesia was continued for 2 days after surgery , and infusion of ketamine or placebo was continued for 3 days . Pain was assessed at 6 , 12 , 24 , and 48 h after surgery . Patients were asked about their pain , abnormal sensation on the wound , and inconvenience in daily life at 7 days and 1 , 3 , and 6 months after surgery . Results : The visual analog scale scores for pain at rest and on coughing 24 and 48 h after thoracotomy were lower in the ketamine group than in the control group ( pain at rest , 9 ± 11 vs. 25 ± 20 and 9 ± 11 vs. 18 ± 13 ; pain on coughing , 26 ± 16 vs. 50 ± 17 and 30 ± 18 vs. 43 ± 18 , mean ± SD ; P = 0.002 and P = 0.01 , P < 0.0001 and P = 0.02 , respectively ) . The numerical rating scale scores for baseline pain 1 and 3 months after thoracotomy were significantly lower in the ketamine group ( 0.5 [ 0–4 ] vs. 2 [ 0–5 ] and 0 [ 0–5 ] vs. 1.5 [ 0–6 ] , median [ range ] , respectively ; P = 0.02 ) . Three months after surgery , a higher number of control patients were taking pain medication ( 2 vs. 9 ; P = 0.03 ) . Conclusions : Very-low-dose ketamine ( 0.05 mg · kg−1 · h−1 ) potentiated morphine-ropivacaine analgesia and reduced postthoracotomy pain Introduction Over 16 000 mastectomies are performed in Engl and and Wales annually . Acute postoperative pain and nausea are common . The most frequently occurring long-term complications are chronic pain ( up to 50 % ) and reduced shoulder function ( reported at 35 % ) . Regional techniques that improve acute postoperative pain relief may reduce the incidence of these complications . This study assesses the effectiveness of a 24-hour continuous local anaesthetic in the subpectoral plane in improving postoperative pain and quality of life in patients undergoing mastectomy . Methods and analysis This is a r and omised , double blind , placebo-controlled , two-centre , parallel group trial in women undergoing mastectomy with or without axillary involvement . One hundred and sixty participants will be r and omised in a 1:1 ratio to receive either 0.25 % levobupivacaine or 0.9 % saline by subpectoral infusion postoperatively for 24 h. All participants will be provided with an intravenous morphine patient-controlled analgesia ( PCA ) system . Participants will be followed-up for 24 h in hospital and at approximately 14 days and 6 months postoperatively . Joint primary outcome measures are total morphine consumption and total pain score ( captured via patient-recorded visual analogue scale ( VAS ) 4 hourly ) during the first 24 h postoperatively . Primary statistical analysis of total pain is based on the area under the curve of pain versus time graph . Secondary outcomes include PCA attempts in first 24 h ; VAS pain scores and shoulder function by goniometry at 24 h , 14 days ( approximately ) and 6 months ; Verbal Rating Scale pain scores in first 24 h ; Brief Pain Inventory and Oxford Shoulder Score at 6 months ; duration of hospital stay ; incidence of postoperative nausea and vomiting ; cost-effectiveness . Ethics and dissemination The study is approved by the South West Engl and Research Ethics Committee ( 12/SW/0149 ) . Results will be published in a peer- review ed journal and presented at local , national and international scientific meetings . Trial registration IS RCT N46621916 . EudraCT 2011 - 005775 - 16 OBJECTIVE The aim of this study was to determine whether the epidural administration of magnesium during the perioperative period decreased the incidence of chronic postoperative pain ( CPOP ) at 3 months after video-assisted thoracic surgery . DESIGN Prospect i ve , r and omized , and blinded . SETTING A university hospital . PARTICIPANTS Patients . INTERVENTIONS Before the induction of anesthesia , the patients were assigned r and omly to receive normal saline , 5 mL , ( group C , n = 72 ) or magnesium sulfate , 100 mg ( group M , n = 72 ) , epidurally . At the end of surgery , group C received a continuous infusion of a mixture of 0.2 % ropivacaine , 226 mL , and fentanyl , 1,200 μg , through a patient-controlled epidural analgesia pump for 48 hours . In group M , magnesium sulfate , 500 mg , was added to the infusion . MEASUREMENTS AND MAIN RESULTS The incidence and severity of CPOP were assessed by a telephone survey 3 months after surgery . Patients were asked whether they experienced pain and to rank the severity of the pain using a 3-point scale ( 1 , mild ; 2 , moderate ; 3 , severe ) . The incidences of CPOP were 42.4 % in group C and 49.1 % in group M. The severities of pain in the patients with CPOP were 1.0 ( 1 - 2 ) in group C and 1.0 ( 1 - 2 ) in group M. The incidence and severity of CPOP did not differ between the 2 groups . CONCLUSIONS The epidural administration of magnesium from before the induction of anesthesia to 48 hours postoperatively did not decrease significantly the incidence or severity of CPOP in patients undergoing video-assisted thoracic surgery Background The laparoscopic repair of ventral hernias can result in significant postoperative pain necessitating a prolonged hospital stay , increased narcotic use , and patient dissatisfaction . Elastomeric pain pump devices with local analgesics may significantly reduce postoperative discomfort after laparoscopic ventral hernia repair . This prospect i ve r and omized , double-blind , placebo-controlled study evaluated the effect of local anesthetic continuously infused with an elastomeric pain pump device to reduce postoperative pain . Methods After institutional review board approval of the study , all patients undergoing laparoscopic ventral hernia repair consented to participate . St and ardized technique included routine transfascial fixation sutures and titanium spiral tacks . Elastomeric pain pumps were placed percutaneously just above the mesh in the hernia sac . For 48 h postoperatively , 100 ml of continuous 0.5 % Marcaine or normal saline was used at 2 ml/h . Postoperatively , the patients were evaluated every 8 h for the first 72 h , then after 2 weeks , 6 weeks , and 3 months for pain scores , narcotic usage ( both oral and intravenous ) , return of flatus , length of hospital stay , and postoperative complications . Results Of the 73 patients enrolled in the study , 37 received 0.5 % Marcaine , and 36 received placebo . Despite r and omization , the control group had significantly more obese patients ( mean body mass index [ BMI ] , 39 vs. 33 kg/m2 ; p = 0.005 ) , and more recurrent hernias ( 40 % vs. 19 % ; p = 0.05 ) , and also tended to have more prior hernia repairs ( 0.8 vs. 0.3 ; p = 0.06 ) . There were no significant differences between the two groups in terms of operative times ( p = 0.7 ) , hernia size ( p = 0.9 ) , mesh size ( p = 0.6 ) , number of transfascial fixation sutures ( p = 0.4 ) , or number of spiral tacks ( p = 0.13 ) . Postoperative visual analog pain scores , usage of oral or intravenous narcotics , and morphine equivalents were similar between the two groups at all study points ( p > 0.05 ) . There were no significant differences between the two groups based on return of bowel function , toleration of a regular diet , or length of hospital stay . No postoperative complications directly related to the catheter were observed . Conclusions This prospect i ve r and omized double-blind , placebo-controlled trial showed no advantage of an elastomeric pain pump device in terms of providing a measurable reduction in postoperative pain scores , narcotic use , time to return of bowel function , or length of hospital stay after laparoscopic ventral hernia repair . Further studies are warranted to determine other alternatives for reducing postoperative pain after laparoscopic ventral hernia repair BACKGROUND AND OBJECTIVES Complex regional pain syndrome ( CRPS ) previously known as reflex sympathetic dystrophy refers to a set of signs and symptoms that include pain , increased sweating , and vasomotor instability . Pain is usually triggered by a noxious stimulus in a peripheral nerve , which is disproportionate to the triggering stimulus . Its development after surgery is not uncommon varying with the type of intervention . An incidence of 2.1 to 5 % has been reported after carpal tunnel release ( CTR ) . Sympathetic blockade may prevent the onset of CRPS . However , there is no study validating this technique to prevent CRPS after CTR . The objective of the present study was to define the incidence of CRPS after CTR and its relationship with four anesthetic techniques . METHODS Patients were r and omly distributed to undergo one of the following techniques : general anesthesia , regional intravenous anesthesia with lidocaine , regional intravenous anesthesia with lidocaine and clonidine , or axillary plexus block . Postoperatively , they were followed-up by a nurse who was unaware of the anesthetic technique used , and follow-up was done through electronic patient records for up to 6 months after the anesthesia . During this period signs and symptoms typical of CRPS were investigated and , if positive , treatment was instituted . A descriptive evaluation using the chi-square test was performed . RESULTS Three-hundred and one patients were investigated . Twenty-five of them developed CRPS , an incidence of 8.3 % . Predominance was not observed among the anesthetic techniques used . Other factors such as smoking , profession , and other concomitant diseases were also investigated , and none showed a relationship with the development of post-CTR CRPS . CONCLUSIONS Complex regional pain syndrome has an incidence of 8.3 % after CTR surgery without association with the anesthetic techniques investigated Background The effect of local infiltration after breast surgery is controversial . This prospect i ve double blind r and omized study sought to document the analgesic effect of local anaesthetic infiltration after breast cancer surgery . Methods Patients scheduled for mastectomy or tumorectomy and axillary nodes dissection had immediate postoperative infiltration of the surgical wound with 20 ml of ropivacaine 7.5 mg.ml-1 or isotonic saline . Pain was assessed on a visual analogue scale at H2 , H4 , H6 , H12 , H24 , H72 , and at 2 month , at rest and on mobilization of the arm . Patient'comfort was evaluated with numerical 0 - 3 scales for fatigue , quality of sleep , state of mood , social function and activity . Results Twenty-two and 24 patients were included in the ropivacaine and saline groups respectively . Postoperative pain was lower at rest and on mobilization at 2 , 4 and 6 hour after surgery in the ropivacaine group . No other difference in pain intensity and patient ' comfort scoring was documented during the first 3 postoperative days . Patients did not differ at 2 month for pain and comfort scores . ConclusionS ingle shot infiltration with ropivacaine transiently improves postoperative pain control after breast cancer surgery . Trial registration PURPOSE Topical anesthetics are widely used in dentistry . One of their indications is to diminish the pain of the injection of anesthetics . Amitriptyline is a tricyclic antidepressant that provides local anesthetic effects by blocking the sodium channels . The present study was performed in an attempt to assess the anesthetic efficacy of an intraoral mucoadhesive tablet of amitriptyline . MATERIAL S AND METHODS The present study was performed as a r and omized , double-blind , placebo-controlled , clinical trial of 25 healthy female volunteers . The mucoadhesive tablet was r and omly placed for 15 minutes on the buccal mucogingival tissue adjacent to the root of the upper lateral incisor , and a placebo was placed on the other side . A 27-gauge needle was inserted to touch the alveolar periosteum of the design ated site . The pain intensity associated with the stimulation was evaluated every 5 minutes after removing the mucoadhesive tablet using a visual analog pain scale and pain rating scoring methods . RESULTS The difference between the amitriptyline and placebo groups was statistically significant 20 , 25 , 30 , 35 , and 40 minutes after placing the mucoadhesive tablet . Its mean onset and duration of action was 25 and 20 minutes , respectively ( P<.05 ) . CONCLUSIONS To our knowledge , the present study represents an initial step toward achieving an efficient and safe anesthetic method . The intraoral mucoadhesive amitriptyline tablet proved to be a promising anesthetic device for manipulating pain in dental procedures . However , it should also be mentioned that to achieve high efficiency , it will be necessary to optimize the release profile This study investigated the incidence and risk factors associated with chronic pain after elective caesarean section under spinal anaesthesia in an Asian population . A prospect i ve cohort study was conducted among subjects who underwent elective caesarean section under spinal anaesthesia , with morphine patient-controlled analgesia administered for 24 hours postoperatively . Perioperative , surgical and obstetric factors were investigated prospect ively . Phone surveys were conducted to identify risk factors associated with chronic pain . A total of 857 subjects completed both the perioperative study and phone survey . The incidence of wound scar pain for three months after surgery was 9.2 % ( 79 ) . Of the 51 subjects with persistent pain at the time of subsequent survey , 9.8 % ( n=5 ) had constant pain , 9.8 % ( n=5 ) had daily pain and 23.5 % ( n=12 ) had pain intermittently , at an interval of days . The independent risk factors for development of chronic pain were higher pain scores recalled in the immediate postoperative period ( odds ratio [ OR , 95 % confidence interval ] 1.348 [ 1.219 to 1.490 ] , P=0.0001 ) , pain present elsewhere ( OR 2.471 [ 1.485 to 4.112 ] , P=0.001 ) and non-private insurance status ( OR 1.679 [ 1.034 to 2.727 ] , P=0.036 ) . The two most common sites of pain other than wound pain were back pain ( n=316 ) and migraine ( n=87 ) Background and objective Local anaesthetics administered intraabdominally have been found to reduce analgesic requirements postoperatively after hysterectomy . This study was design ed to assess the optimal dose of local anaesthetics for best pain relief . Methods Sixty patients undergoing abdominal hysterectomy were r and omly divided into three groups to receive 10 ml h−1 infusion of levobupivacaine intraabdominally postoperatively for 48 h in a double-blind manner : group L , 7.5 mg h−1 ; group M , 12.5 mg h−1 and group H , 17.5 mg h−1 . Pain intensity was measured using the numeric rating scale , ketobemidone consumption over 48 h was measured with a patient-controlled analgesia pump , recovery parameters , expiratory muscle strength , time to home readiness , plasma concentration of levobupivacaine and health-related quality of life were all measured at defined time points postoperatively . Results No differences were found between the active groups in pain intensity , recovery parameters or health-related quality of life . Pain intensity was maximal during 0–4 h and during coughing . Expiratory muscle strength decreased significantly during 0–4 h in all active groups , with no differences between the groups . Plasma concentration of levobupivacaine was below known toxic concentrations in humans , and no patient had symptoms of local anaesthetic toxicity . Health-related quality of life showed improved scores at 3 months after the operation compared with preoperative values , but no differences between the groups were found in any of the parameters . Conclusion Satisfactory analgesia can be achieved with low doses of levobupivacaine administered intraabdominally , except during the early postoperative period . No advantages were seen in this study when higher doses of levobupivacaine were administered as a continuous infusion for postoperative pain relief Longitudinal data from a clinical trial were analyzed to evaluate the usefulness of the SF-36 Health Survey in estimating the impact of depression and changes in severity over time on the functional health and well-being of 532 patients , 60 to 86 years of age , who met DSM-III-R criteria for major depressive disorder . The Hamilton Depression Rating Scale , the Clinician 's Global Impression of Severity and Improvement , and the Geriatric Depression Scale were used to define clinical severity and changes in severity over a 6-week period . Answers to SF-36 questions tended to be complete and to satisfy assumptions underlying methods of scale construction and scoring . As hypothesized , the SF-36 Mental Health Scale and Mental Component Summary measure , shown in previous studies to be most valid in measuring differences in mental health , exhibited the strongest associations with severity of depression in cross-sectional analyses and were most responsive to changes in severity in longitudinal comparisons . We conclude that the SF-36 Health Survey is useful for estimating the burden of depression and in monitoring changes in functional health and well-being over time among the depressed elderly In this clinical , r and omized , prospect i ve study , we compared the effects of three different analgesia techniques ( thoracic epidural analgesia [ TEA ] with and without preoperative initiation and IV patient-controlled analgesia [ IV-PCA ] ) on postthoracotomy pain in 69 patients . In two groups , a thoracic epidural catheter was inserted preoperatively . Group Pre-TEA had bupivacaine and morphine solution preoperatively and intraoperatively . Postoperative analgesia was maintained with epidural PCA with a similar solution . Group Post-TEA , with no intraoperative medication , had the same postoperative analgesia as Group Pre-TEA plus the bolus dose . Group IV-PCA received only IV-PCA with morphine for postoperative analgesia . Pain was evaluated every 4 h during the first 48 h at rest , cough , and movement . Pre-TEA was associated with decreased pain compared with the other groups . Six months later , the patients were asked about their pain . The incidence and the intensity of pain were most frequent in Group IV-PCA ( 78 % ) and were the least in Group Pre-TEA ( 45 % ) ( Group Pre-TEA versus Group IV-PCA , P = 0.0233 ; Group Pre-TEA versus Group IV-PCA , P = 0.014 ) . Patients having pain on the second postoperative day had 83 % chronic pain . TEA with preoperative initiation is a preferable method in preventing acute and long-term thoracotomy pain Background : The authors tested the primary hypothesis that perioperative IV lidocaine administration during spine surgery ( and in the postanesthesia care unit for no more than 8 h ) decreases pain and /or opioid requirements in the initial 48 postoperative hours . Secondary outcomes included major complications , postoperative nausea and vomiting , duration of hospitalization , and quality of life . Methods : One hundred sixteen adults having complex spine surgery were r and omly assigned to perioperative IV lidocaine ( 2 mg·kg−1·h−1 ) or placebo during surgery and in the postanesthesia care unit . Pain was evaluated with a verbal response scale . Quality of life at 1 and 3 months was assessed using the Acute Short-form ( SF ) 12 health survey . The authors initially evaluated multivariable bidirectional noninferiority on both outcomes ; superiority on either outcome was then evaluated only if noninferiority was established . Results : Lidocaine was significantly superior to placebo on mean verbal response scale pain scores ( P < 0.001 ; adjusted mean [ 95 % CI ] of 4.4 [ 4.2 - 4.7 ] and 5.3 [ 5.0 - 5.5 ] points , respectively ) and significantly noninferior on mean morphine equivalent dosage ( P = 0.011 ; 55 [ 36 - 84 ] and 74 [ 49 - 111 ] mg , respectively ) . Postoperative nausea and vomiting and the duration of hospitalization did not differ significantly . Patients given lidocaine had slightly fewer 30-day complications than patients given placebo ( odds ratio [ 95 % CI ] of 0.91 [ 0.84–1.00 ] ; P = 0.049 ) . Patients given lidocaine had significantly greater SF-12 physical composite scores than placebo at 1 ( 38 [ 31–47 ] vs. 33 [ 27–42 ] ; P = 0.002 ) and 3 ( 39 [ 31–49 ] vs. 34 [ 28–44 ] ; P = 0.04 ) months , postoperatively . Conclusion : IV lidocaine significantly improves postoperative pain after complex spine surgery BACKGROUND Intrathecal morphine is an effective analgesic post-cesarean delivery ; however , it may be contraindicated or unsuitable in some patients . We compared the efficacy and side effects of intrathecal morphine with an ultrasound-guided transversus abdominis plane ( TAP ) block in a r and omized , controlled , double-blinded trial . The primary outcome was the morphine equivalents dose used in the first 24 h post-surgery . Secondary outcomes were pain scores and side effects , including pruritus , sedation , nausea and vomiting . METHODS Planned recruitment was for 90 women ; however , the study was terminated early . Sixty-nine women undergoing elective cesarean delivery under spinal anesthesia were enrolled . They were r and omized to receive either intrathecal morphine 100 μg plus a sham TAP block or a TAP block with 0.5 % ropivacaine 1.5 mg/kg , to each side to a maximum of 20 mL. Women were assessed at 2 , 6 , 10 , 24 h and 3 months post-spinal . RESULTS Sixty-six women completed the trial . The morphine equivalents dose used in the TAP block group was greater at 24 h compared with the intrathecal morphine group ( 7.5 mg ( 95 % CI 4.8 - 10.2 ) vs. 2.7 mg ( 95 % CI 1.0 - 4.3 ) , F [ 1 , 64]=9.62 , P=0.003 ) . There was no difference at 2 , 6 , or 10 h. Pain scores on rest and movement were higher in the TAP block group at all times although this only reached statistical significance at 10 h ( P=0.001 ) . Nausea and vomiting ( P=0.02 ) and pruritus ( P=0.007 ) were lower in the TAP block group . CONCLUSIONS In this trial , the TAP block was associated with greater supplemental morphine requirements and higher pain scores than intrathecal morphine but fewer opioid-related side effects . The TAP block may be a reasonable alternative when intrathecal morphine is contraindicated or not appropriate Post thoracotomy chronic pain is a severe problem that affects the majority of patients and decreases the quality of life . The purpose of this study is to evaluate the long-term effects of thoracal epidural levobupivacaine and intravenous dexketoprofen analgesia formed pre-emptively on the wound site pain after major thoracotomy operations . This r and omised , prospect i ve and double-blind study was performed with 60 patients undergoing thoracic surgery . Patients were divided into three groups ; Control Group ( Group C ) , Pre-emptive Epidural Group ( Group PE ) and Pre-emptive Dexketoprofen + Epidural Group ( Group PED ) . Patients in the Group C did not receive epidural analgesics and i.v . dexketoprofen before and during the operation . 10 - 15 ml 0.125 % levobupivacaine was given to cases in Group PE pre-emptively through epidural catheter before the anesthesia induction . The cases in Group PED were given 10 - 15 ml 0.125 % epidural levobupivacaine and 50 mg dexketoprofen with i.v . infusion pre-emptively . The VAS score was found to be lower in Group PED during postoperative 24 and 48 hours and before the discharge ( P<0.05 ) . The VAS score was similar in all groups during the first and third months ( P>0.05 ) . A statistically significant decrease was determined in the VAS score in Group PED during the sixth month , compared to the other groups ( P<0.05 ) . When the scores of Patient Satisfaction Scale ( PSS ) of the cases were compared , they were found to be higher in Group PED as statistically significant during the discharge period ( P<0.001 ) . Scores of PSS were higher in Group PED as statistically significant during the postoperative month 6 ( P = 0.008 ) . Combined application of pre-emptive intravenous dexketoprofen and thoracal epidural analgesia reduce the chronic post-thoracotomy pain BACKGROUND Transversus abdominis plane ( TAP ) block has been reported to provide effective analgesia after lower abdominal surgery , but there are few data comparing ilioinguinal/iliohypogastric nerve ( IHN ) block with ultrasound-guided TAP block in patients undergoing inguinal hernia repair . METHODS Two hundred and seventy-three patients undergoing day-case open inguinal hernia repair with a mesh were r and omly allocated to receive either ultrasound-guided TAP block or blind IHN block with levobupivacaine 0.5 % , before surgery . Patients were monitored for visual analogue scale ( VAS ) scores at rest ( in the post-anaesthesia care unit , and at 4 and 12 h ) and at rest and during movement ( at 24 , 48 h , 3 and 6 months ) . Pain at 6 months was also assessed using the DN4 question naire for neuropathic pain . RESULTS Median VAS pain scores at rest were lower in the ultrasound-guided TAP group at 4 h ( 11 vs 15 , P=0.04 ) , at 12 h ( 20 vs 30 , P=0.0014 ) , and at 24 h ( 29 vs 33 , P=0.013 ) . Pain after the first 24 h , at 3 and 6 months after surgery , and DN4 scores were similar in both groups ( P = NS ) . The proportion of patients with VAS > 40 mm on movement at 6 months was comparable { 18.2 % [ 95 % CI ( 12.2 - 26.1 % ) ] vs 22.4 % ( 15.8 - 30.6 % ) in the TAP and IHN groups , respectively , P=0.8}. Postoperative morphine requirements were lower during the first 24 h in the TAP block group ( P=0.03 ) . CONCLUSIONS Ultrasound-guided TAP block provided better pain control than ' blind ' IHN block after inguinal hernia repair but did not prevent the occurrence of chronic pain Background : Autologous breast reconstruction by deep inferior epigastric perforator ( DIEP ) flap provides higher postoperative pain at the abdominal donor site than at the thoracic one . The authors evaluated the analgesic efficacy of ultrasound-guided transverse abdominis plane block for postoperative analgesia after immediate breast reconstruction by DIEP flap . Methods : The authors conducted an open prospect i ve study of 30 consecutive women undergoing immediate DIEP flap breast reconstruction after modified radical mastectomy for cancer . The last 15 patients received a bilateral ultrasound-guided block with 1.5 mg/kg ropivacaine on each side after DIEP flap harvesting , under general anesthesia . All patients received postoperative acetaminophen and patient-controlled intravenous morphine and were assessed for morphine use , satisfaction with pain relief , and adverse effects . Results : Morphine requirements were significantly lower in the block group than in the control group for the 0- to 12-hour ( 17.7 mg versus 22.7 mg , p = 0.0047 ) and 12- to 24-hour ( 14.2 mg versus 17.4 mg , p = 0.01 ) intervals but not for the 24- to 36-hour ( 11.3 mg versus 12.2 mg , p = 0.30 ) and 36- to 48-hour ( 8.6 mg versus 8.4 mg , p = 0.65 ) intervals . Cumulative morphine use was lower in the block group than in the control group for the first 24 hours ( 32.0 mg versus 40.2 mg , p = 0.0057 ) and the first 48 hours ( 51.7 mg versus 60.5 mg , p = 0.03 ) . There was no complication attributable to the block , with an average follow-up of 9 months . Conclusions : Bilateral ultrasound-guided transversus abdominis plane block after breast reconstruction by DIEP flap reduces the interval and cumulative morphine requirements for the first 24 and 48 hours , respectively . CLINICAL QUESTION /LEVEL OF EVIDENCE : Therapeutic , II . Figure . No caption available In r and omised controlled trials , allocation concealment ( separating the process of r and omisation from the recruitment of participants ) is important for rigorously design ed trials.1–4 In 1996 many major medical journals adopted the CONSORT statement ( whereby research ers have to include a short checklist of essential items and a flow diagram when reporting trials),5 and this move encouraged the reporting of allocation concealment . We review ed the prevalence of adequate allocation concealment and its association with the statistical significance of trial results . We search ed by h and four general medical journals ( the BMJ , JAMA , the Lancet , and the New Engl and Journal of Medicine ) to identify r and omised controlled trials published from January 2002 to December 2002 . We included articles if the authors reported that participants were r and omised and if the trial was published as a full report with the results of the main analyses . We categorised articles according to whether allocation concealment was adequate ( the person who executed the allocation sequence was different from the person who recruited Background One of the modalities of treatment for breast cancer surgery pain is opioids , and opioids are associated with adverse effects such as itching and postoperative nausea and vomiting ( PONV ) . Intravenous ( IV ) lidocaine has been shown to reduce opioid consumption and to improve overall postoperative outcomes in abdominal surgery . In this study , we tested the effect of intraoperative IV lidocaine infusion on the quality of postoperative recovery after breast cancer surgery . Methods Seventy-one patients undergoing breast cancer surgery were r and omly assigned to receive either placebo ( group P ; n = 34 ) or IV lidocaine ( group L ; n = 37 , bolus 1.5 mg/kg at induction , then infusion at 2 mg/kg/h , stopped 2 hours after the end of surgery ) in a prospect i ve double-blind design . Intraoperative and postoperative morphine consumption was calculated . Postoperative pain scores , PONV , and fatigue were assessed at 2 , 24 , and 48 hours after surgery . Duration of postoperative hospital stay was recorded . Results Demographics were the same between the groups . There was no statistically significant difference in intraoperative or postoperative morphine consumption ( P = 0.188 and P = 0.758 ) between groups . Overall pain scores either at rest or activity ( P = 0.348 and P = 0.810 , respectively ) , PONV ( P = 0.350 ) , fatigue ( P = 0.758 ) , or duration of postoperative hospital stay ( P = 0.218 ) were not statistically different . Conclusions Our findings did not show a significant effect of IV lidocaine during breast cancer surgery on opioid consumption , pain score , PONV , or fatigue , indicating that the benefit of this approach does not generalize across all types of surgery OBJECTIVE Long-term pain is a common sequela of thoracotomy , occurring in approximately 50 % of patients 2 years after thoracic surgery . Despite this alarming statistic , little is known about the factors responsible for the transition of acute to chronic pain . The aim of the present study is to identify predictors of long-term post-thoracotomy pain . DESIGN Follow-up was for 1.5 years for patients who had participated in a prospect i ve , r and omized , controlled trial of preemptive , multimodal analgesia . SETTING Subjects were recruited from a tertiary care center . PATIENTS Thirty patients who had undergone lateral thoracotomy were followed up by telephone , administered a structured interview , and classified according to long-term pain status . MAIN OUTCOME MEASURES Present pain status was measured by a verbal rating scale ( VAS ) . Measures obtained within the first 48 h after surgery were compared between patients with and without pain 1.5 years later . These include VAS pain scores at rest and after movement , McGill Pain Question naire data , patient-controlled morphine consumption ( mg ) , and pain thresholds to pressure applied to a rib contralateral to the thoracotomy incision . RESULTS Fifty-two percent of patients reported long-term pain . Early postoperative pain was the only factor that significantly predicted long-term pain . Pain intensity 24 h after surgery , at rest , and after movement was significantly greater among patients who developed long-term pain compared with pain-free patients . A significant predictive relationship was also found at 24 and 48 h using the McGill Pain Question naire . Cumulative morphine was comparable for the two groups . Pain thresholds to pressure applied to a rib contralateral to the incision did not differ significantly between the groups . CONCLUSION Aggressive management of early postoperative pain may reduce the likelihood of long-term post-thoracotomy pain We have examined the effect of preoperative extradural bupivacaine and morphine on postoperative stump sensation in 31 patients undergoing amputation of the lower limb in a prospect i ve , r and omized , double-blind study . Patients were allocated r and omly to one of two groups : group 1 received extradural 0.25 % bupivacaine 4 - 7 ml h-1 and morphine 0.16 - 0.28 ml h-1 before and during operation ; group 2 received extradural saline before and during amputation and conventional analgesics for pain treatment . All patients received general anaesthesia for the amputation and extradural bupivacaine and morphine after operation . Sensory examination of the limb/stump was carried out before amputation , and after 1 week and 6 months . The following were measured : pressure pain thresholds ( pressure algometry ) , touch and pain detection thresholds ( von Frey hairs ) , thermal sensibility ( thermal rolls ) , and allodynia and wind-up-like pain . There were no differences between the two groups at any of the postoperative assessment s for mechanical and thermal sensibility or rate of allodynia and wind-up-like pain . Our study suggests that preoperative and intraoperative extradural block had no long-term prophylactic effect on hyperalgesia , allodynia or wind-up-like pain STUDY OBJECTIVE We investigated if human reminder phone calls in the patient 's preferred language increase adherence with scheduled appointments in an inner-city chronic pain clinic . We hypothesized that language and cultural incongruence is the underlying mechanism to explain poor attendance at clinic appointments in underserved Hispanic population s. DESIGN Pragmatic r and omized controlled clinical trial SETTING : Innercity academic chronic pain clinic with a diverse , predominantly African-American and Hispanic population PATIENTS : All ( n=963 ) adult patients with a scheduled first appointment between October 2014 and October 2015 at the Montefiore Pain Center in the Bronx , New York were enrolled . INTERVENTIONS Patients were r and omized to receive a human reminder call in their preferred language before their appointment , or no contact . MEASUREMENTS We recorded patients ' demographic characteristics and as primary outcome attendance as scheduled , failure to attend and /or cancellation calls . We fit Bayesian and classical multinomial logistic regression models to test if the intervention improved adherence with scheduled appointments . MAIN RESULTS Among the 953 predominantly African American and Hispanic/Latino patients , 475 patients were r and omly selected to receive a language -congruent , human reminder call , while 478 were assigned to receive no prior contact , ( after we excluded 10 patients , scheduled for repeat appointments ) . In the experimental group , 275 patients adhered to their scheduled appointment , while 84 cancelled and 116 failed to attend . In the control group , 249 patients adhered to their scheduled appointment , 31 cancelled and 198 failed to attend . Human phone reminders in the preferred language increased adherence ( RR 1.89 , CI95 % [ 1.42 , 1.42 ] , ( p<0.01 ) . The intervention seemed particularly effective in Hispanic patients , supporting our hypothesis of cultural congruence as possible underlying mechanism . CONCLUSIONS Human reminder phone calls prior in the patient 's preferred language increased adherence with scheduled appointments . The intervention facilitated access to much needed care in an ethnically diverse , re source poor population , presumably by overcoming language barriers ABSTRACT The objective of the present research was to develop a single measure of the major symptoms of both neuropathic and non‐neuropathic pain that can be used in studies of epidemiology , natural history , pathophysiologic mechanisms , and treatment response . We exp and ed and revised the Short‐form McGill Pain Question naire1 ( SF‐MPQ ) pain descriptors by adding symptoms relevant to neuropathic pain and by modifying the response format to a 0–10 numerical rating scale to provide increased responsiveness in longitudinal studies and clinical trials . The reliability , validity , and subscale structure of the revised SF‐MPQ ( SF‐MPQ‐21 ) were examined in responses from 882 individuals with diverse chronic pain syndromes and in 226 patients with painful diabetic peripheral neuropathy who participated in a r and omized clinical trial . The data suggest that the SF‐MPQ‐2 has excellent reliability and validity , and the results of both exploratory and confirmatory factor analyses provided support for four readily interpretable subscales — continuous pain , intermittent pain , predominantly neuropathic pain , and affective descriptors . These results provide a basis for use of the SF‐MPQ‐2 in future clinical research , including clinical trials of treatments for neuropathic and non‐neuropathic pain conditions Abstract Background Local anesthetic infiltration has been used to manage postoperative pain in various surgeries . The present study was aim ed to investigate the effect of skin infiltration with 0.5 % ropivacaine on postoperative pain in patients undergoing craniotomy . Methods One hundred and six patients with ASA I/II scheduled to undergo elective craniotomy were enrolled during March to November in 2015 in this prospect i ve , r and omized , placebo-controlled , double-blind study . After the anesthesia induction , skin along the incision was infiltrated with 0.5 % ropicavaine ( group R , n = 53 ) or 0.9 % normal saline ( group C , n = 53 ) , respectively . Morphine was used as rescue analgesic postoperatively . Morphine consumption during the first 24 postoperative hours was recorded as the primary outcome , and the time to first rescue requirement was also recorded . Pain was assessed at 2 , 4 , 8 , 24 h , 7 days , 3 months after surgery by visual analog scale ( VAS ) . Heart rate and mean arterial pressure were recorded before anesthesia induction ( T1 ) , after anesthesia induction ( T2 ) , after scalp infiltration ( T3 ) , during skull drilling ( T4 ) , mater cutting ( T5 ) and skin closure ( T6 ) . Results Morphine consumption during the first 24 postoperative hours was significantly higher in group C than in group R ( 13.36 [ 6.5 , 20 ] vs. 6.3 [ 0 , 10 ] mg , P < 0.05 ) . The first time of patients needed rescue analgesic was prolonged in group R as compared with group C ( 6.16 [ 3.4 , 8.0 ] vs. 3.87 [ 2.3 , 4 ] h , P < 0.05 ) . Postoperative VAS and hemodynamic signs during the first 24 h showed no significant difference in two groups . The incidence of persistent pain on 7 days and 3 months postoperatively had no significant differences between two groups . Besides one patient ( 2 % ) enduring moderate pain ( VAS 4–7 ) in group C , the number of patients suffering from mild pain ( VAS 1–3 ) was 17 ( 33.3 % ) in group R and 17 ( 34 % ) in group C 3 months after surgery . Conclusion The results suggest 0.5 % ropivacaine scalp infiltration before skin incision has favorable analgesic effect in reducing morphine consumption and prolong the time of first rescue analgesic requirement after surgery . Trial registration Chinese Clinical Trial Registry ( http://www.chictr.org.cn/ ) registration number : Epidural analgesia is regarded as the gold method for controlling post‐thoracotomy pain . Intercostal nerve cryoanalgesia can also produce satisfactory analgesic effects , but is suspected to increase the incidence of chronic pain . However , r and omized controlled trials comparing these two methods for post‐thoracotomy acute pain analgesic effects and chronic pain incidents have not been conducted previously . We studied 107 adult patients , allocated r and omly to thoracic epidural bupivacaine and morphine or intercostal nerve cryoanalgesia . Acute pain scores and opioid‐related side effects were evaluated for three postoperative days . Chronic pain information , including the incidence , severity , and allodynia‐like pain , was acquired on the first , third , sixth and twelfth months postoperatively . There was no significant difference on numeral rating scales ( NRS ) at rest or on motion between the two groups during the three postoperative days . The patient satisfaction results were also similar between the groups . The side effects , especially mild pruritus , were reported more often in the epidural group . Both groups showed high incidence of chronic pain ( 42.1–72.1 % ) , and no significance between the groups . The incidence of allodynia‐like pain reported in cryo group was higher than that in Epidural group on any postoperative month , with significance on the sixth and the twelfth months postoperatively ( P<0.05 ) . More patients rated their chronic pain intensity on moderate and severe in cryo group and interfered with daily life ( P<0.05 ) . Both thoracic epidural analgesia and intercostal nerve cryoanalgesia showed satisfactory analgesia for post‐thoracotomy acute pain . The incidence of post‐thoracotomy chronic pain is high . Cryoanalgesia may be a factor that increases the incidence of neuropathic pain Purpose To examine the effect of continuous epidural block initiated before thoracic surgery upon early and long-term postoperative pain . Methods In a double-blind study , 70 patients scheduled for thoracic surgery under general anesthesia were assigned r and omly to receive continuous epidural block with mepivacaine 1.5 % initiated either 20 min before surgical incision ( Pre group ) or at completion of surgery ( Post group ) . In both groups the initial dose was 4 ml , followed by a continuous infusion at 4 ml·hr−1 until 72 hr after operation . Indomethadn suppositories , 50 mg , were administered on request as supplementary analgesics . Visual analogue scale at rest was assessed four hours after operation , and then every 24 hr after operation on postoperative days 1 through 7 , and also days 14 and 30 . At three and six months after operation , all patients were interviewed by telephone with respect to postoperative pain . The most severe pain was assessed using modified numerical rating scale . Results By a visual analogue scale , postoperative pain was less in the Pre group than in the Post group at four hours , two and three days after operation ( P < 0.05 ) . By a numerical rating scale six months after operation , pain was less in the Pre group than in the Post group ( P = 0.015 ) . The percentage of pain-free patients was higher in the Pre group than in the Post group at three ( P = 0.035 ) and six ( P = 0.0086 ) months after operation . Conclusion Continuous epidural block initiated prior to surgery may reduce long-term post-thoracotomy pain . RésuméObjectifExaminer l’effet d’un blocage épidural continu , amorcé avant une intervention chirurgicale thoracique , sur la douleur postopératoire précoce et de long terme . MéthodeLétude à double insu a porté sur 70 patients qui devaient subir une opération thoracique sous anesthésie générale . Répartis au hasard , ils ont reçu un blocage épidural continu avec de la mépivacaïne à 1,5 % , administrée soit 20 min avant l’incision chirurgicale ( groupe Pré ) , soit à la fin de l’intervention ( groupe Post ) . Pour tous , la dose initiale a été de 4 ml suivie d’une perfusion continue à 4 ml·hr−1 jusqu’à 72 h après l’opération . Des suppositoires de 50 mg d’indométhacine ont été administrés sur dem and e pour compléter l’analgésie . La douleur a été évaluée au repos selon l’échelle visuelle analogique , 4 h après l’opération et puis à toutes les 24 h des jours 1 à 7 et aussi les jours 14 et 30 . Trois mois et six mois après l’opération , tous les patients ont été interrogés par téléphone au sujet de la douleur postopératoire . La douleur la plus sévère a été évaluée en utilisant une échelle d’estimation numérique modifiée . RésultatsSelon l’échelle visuelle analogique , la douleur postopératoire était plus faible chez les patients du groupe Pré que chez ceux du groupe Post à 4 h , deux et trois jours après l’opération ( P < 0,05 ) . Selon une échelle d’estimation numérique , la douleur était moins intense chez les patients du groupe Pré que chez ceux du groupe Post ( P = 0,015 ) six mois après l’opération . Le pourcentage de patients sans douleur était plus élevé dans le groupe Pré que dans le groupe Post à trois mois ( P = 0,035 ) et à six mois ( P = 0,0086 ) après l’opération . Conclusion Le blocage épidural continu amorcé avant l’intervention chirurgicale peut réduire la douleur qui se prolonge après une thoracotomie Background and Objectives Acute stump pain and phantom limb pain after amputation is a significant problem among amputees with a reported incidence of phantom limb pain in the first year following amputation as high as 70 % . Epidural analgesia before limb amputation is commonly used to reduce postamputation acute stump pain in the immediate postoperative period and phantom pain in the first year . We investigated whether immediate postamputation stump pain and phantom pain in the first year is reduced by preoperative epidural block with bupivacaine and diamorphine compared with intraoperative placement of a perineural catheter infusing bupivacaine . Methods In a r and omized prospect i ve trial , 30 patients scheduled for lower limb amputation were r and omly assigned epidural bupivacaine at the st and ard rate used in our hospital ( 0.166 % , 2 to 8 mL/h ) and diamorphine ( 0.2 to 0.8 mg/h ) for 24 hours before and during operation ( 14 patients ; epidural group ) and 3 days postoperatively , or an intraoperatively placed perineural catheter ( 16 patients ; perineural group ) for intra and postoperative administration of bupivacaine ( 0.25 % , 10 mL/h ) . All patients had general anesthesia for the amputation and were asked about stump and phantom pain in the first 3 days and then at 6 and 12 months by an independent examiner . Study endpoints were rate of stump and phantom pain , intensity of stump and phantom pain , and consumption of opioids . The groups were well matched in baseline characteristics . Results Stump pain scores in the first 3 days were significantly higher in the perineural group compared with the epidural group ( P < .01 ) . After 3 days , 4 ( 29 % ) patients in the epidural group and 7 ( 44 % ) in the perineural group had phantom pain ( P = .32 ) . Numbers of patients with phantom pain for epidural versus perineural group were : 5 ( 63 % ) versus 7 ( 88 % ) ( P = .25 ) at 6 months ; 3 ( 38 % ) versus 4 ( 50 % ) ( P = .61 ) at 12 months . Stump pain and phantom sensation were similar in both groups at 6 and 12 months . Conclusions Using our regimen , perioperative epidural block started 24 hours before the amputation is not superior to infusion of local anaesthetic via a perineural catheter in preventing phantom pain , but gives better relief of stump pain in the immediate postoperative period Background Pain following thoracotomy can persist for years with an undetermined impact on quality of life . Factors hypothesized to modulate this painful experience include analgesic regimen , gender , and type of incision . Methods A total of 157 generally healthy patients of both genders scheduled for segmentectomy , lobectomy , or bilobectomy through a posterolateral or muscle-sparing incision were r and omly assigned to receive thoracic epidural analgesia initiated prior to incision or at the time of rib approximation . Pain and activity scores were obtained 4 , 8 , 12 , 24 , 36 , and 48 weeks after surgery . Results Overall , there were no differences in pain scores between the control and intervention groups during hospitalization ( P ≥ 0.165 ) or after discharge ( P ≥ 0.098 ) . The number of patients reporting pain 1 yr following surgery ( 18 of 85 ; 21.2 % ) was not significantly different ( P = 0.122 ) from the number reporting preoperative pain ( 15 of 120 ; 12.5 % ) . During hospitalization , women reported greater pain than men ( worst pain , P = 0.007 ; average pain , P = 0.016 ) . Women experienced fewer supraventricular tachydysrhythmias ( P = 0.013 ) and were thus discharged earlier ( P = 0.002 ) . After discharge women continued to report greater discomfort than men ( P ≤ 0.016 ) , but did not differ from men in their level of physical activity ( P = 0.241 ) . Conclusions Initiation of thoracic epidural analgesia prior to incision or the use of a muscle-sparing incision did not significantly impact pain or physical activity . Although women reported significantly greater pain during hospitalization and after discharge , they experienced fewer complications , were more likely to be discharged from the hospital sooner , and were just as active after discharge as men Introduction We aim ed to compare the effects of intraoperative lidocaine and magnesium on postoperative functional recovery and chronic pain after mastectomy due to breast cancer . Systemic lidocaine and magnesium reduce pain hypersensitivity to surgical stimuli ; however , their effects after mastectomy have not been evaluated clearly . Methods In this prospect i ve , double-blind , clinical trial , 126 female patients undergoing mastectomy were r and omly assigned to lidocaine ( L ) , magnesium ( M ) , and control ( C ) groups . Lidocaine and magnesium were administered at 2 mg/kg and 20 mg/kg for 15 minutes immediately after induction , followed by infusions of 2 mg/kg/h and 20 mg/kg/h , respectively . The control group received the same volume of saline . Patient characteristics , perioperative parameters , and postoperative recovery profiles , including the Quality of Recovery 40 ( QoR-40 ) survey , pain scales , length of hospital stay , and the short-form McGill pain question naire ( SF-MPQ ) at postoperative 1 month and 3 months were evaluated . Results The global QoR-40 scores on postoperative day 1 were significantly higher in group L than in group C ( P = 0.003 ) . Moreover , in sub-scores of the QoR-40 dimensions , emotional state and pain scores were significantly higher in group L than those in groups M and C ( P = 0.027 and 0.023 , respectively ) . At postoperative 3 months , SF-MPQ and SF-MPQ-sensitive scores were significantly lower in group L than in group C ( P = 0.046 and 0.036 , respectively ) . Conclusions Intraoperative infusion of lidocaine improved the quality of recovery and attenuated the intensity of chronic pain in patients undergoing breast cancer surgery Objective . To determine whether postoperative symptoms differ between women who undergo abdominal benign hysterectomy in a fast‐track model under general anesthesia or spinal anesthesia with intrathecal morphine . Design . Secondary analysis from a r and omized , open , multicenter study . Setting . Five hospitals in south‐east Sweden . Population . One‐hundred and eighty women scheduled for benign hysterectomy were r and omized ; 162 completed the study ; 82 were allocated to spinal and 80 to general anesthesia . Methods . The Swedish Postoperative Symptoms Question naire , completed daily for 1 week and thereafter once a week until 5 weeks postoperatively . Main Outcome Measures . Occurrence , intensity and duration of postoperative symptoms . Results . Women who had hysterectomy under spinal anesthesia with intrathecal morphine experienced significantly less discomfort postoperatively compared with those who had the operation under general anesthesia . Spinal anesthesia reduced the need for opioids postoperatively . The most common symptoms were pain , nausea and vomiting , itching , drowsiness and fatigue . Abdominal pain , drowsiness and fatigue occurred significantly less often and with lower intensity among the spinal anesthesia group . Although postoperative nausea and vomiting was reported equally in the two groups , vomiting episodes were reported significantly more often during the first day after surgery in the spinal anesthesia group . Spinal anesthesia was associated with a higher prevalence of postoperative itching . Conclusions . Spinal anesthesia with intrathecal morphine carries advantages regarding postoperative symptoms and recovery following fast‐track abdominal hysterectomy Background : Most studies of preemptive or preventive analgesia restrict outcomes to pain and analgesic consumption in the acute postoperative period . The potential longer-term effects on these and other domains of functioning have received little empirical attention . The purpose of this study was to follow up patients who had received general anesthesia plus epidural fentanyl and lidocaine before ( group 1 ) or after ( group 2 ) incision or general anesthesia plus a sham epidural ( group 3 ) . Methods : Patients were contacted approximately 3 weeks and 6 months after surgery . A follow-up pain question naire and the McGill Pain Question naire were administered by telephone . The Mental Health Inventory and Pain Disability Index were mailed to patients , completed , and mailed back . Results : One hundred thirty-one of the 141 patients ( 93 % ) were reached 3 weeks after surgery ( n = 41 , n = 48 , and n = 42 in groups 1 , 2 , and 3 , respectively ) , and 109 ( 77 % ) were reached at 6 months ( n = 35 , n = 37 , and n = 37 in groups 1 , 2 , and 3 , respectively ) . Multivariate analysis of covariance indicated that that even after controlling for age and presence or absence of preoperative pain , Pain Disability Index scores ( mean ± SD ) at the first follow-up were significantly lower in group 1 ( 17.3 ± 12.8 ) and group 2 ( 18.1 ± 17.0 ) compared with group 3 ( 26.3 ± 18.3 ) . McGill Pain Question naire and Mental Health Inventory scores did not differ significantly among the groups . There were no significant differences at the 6-month follow-up . Conclusion : The short-term beneficial effects of preventive epidural analgesia translated into less pain disability 3 weeks after surgery . Progress in underst and ing the processes involved in postsurgical recovery and the risk factors for chronic postsurgical pain would be aided by baseline and postsurgical measures of relevant psychological , emotional , and physical variables Background Inguinal hernia repair is one of the most frequently performed procedures in Switzerl and ( 15'000/year ) . The most common complication postoperatively is development of chronic pain in up to 30 % of all patients irrespective of the operative technique . Methods / Design 264 patients scheduled for an inguinal hernia repair using one of three procedures ( Lichtenstein , Barwell and TEP = total extraperitoneal hernioplasty ) are being r and omly allocated intra-operatively into two groups . Group I patients receive a local injection of 20 ml Carbostesin ® 0.25 % at the end of the operation according to a st and ardised procedure . Group II patients get a 20 ml placebo ( 0.9 % Saline ) injection . We use pre-filled identically looking syringes for blinded injection , i.e. the patient , the surgeon and the examinator who performs the postoperative clinical follow-ups remain unaware of group allocation . The primary outcome of the study is the occurrence of developing chronic pain ( defined as persistent pain at 3 months FU ) measured by VAS and Pain Matcher ® device ( Cefar Medical AB , Lund , Sweden).The study started on July 2006 . In addition to a sample size re-evaluation three interim analyses are planned after 120 , 180 and 240 patients had finished their 3-months follow-up to allow for early study termination . Discussion Using a group sequential study design the minimum number of patients are enrolled to reach a valid conclusion before the end of the study .To limit subjectivity , both a VAS and the Pain Matcher ® device are used for the evaluation of pain . This allows us also to compare these two methods and further assess the use of Pain Matcher ® in clinical routine . The occurrence of chronic pain after inguinal hernia repair has been in focus of several clinical studies but the reduction of it has been rarely investigated . We hope to significantly reduce the occurrence of this complication with our investigated intervention . Trial Registration Our trial has been registered at Clinical Trials.gov . The trial registration number is : [ NCT00484731 ] Thoracotomy is often responsible for chronic pain , possibly of neuropathic origin . To confirm pre clinical studies , the preventive effects of perioperative ketamine were tested in a r and omized , double‐blind , placebo‐controlled clinical trial on persistent neuropathic pain after thoracotomy . Eighty‐six patients scheduled for thoracotomy under st and ardised general anaesthesia were r and omised to receive either ketamine ( 1mgkg−1 at the induction , 1mgkg−1h−1 during surgery , then 1mgkg−1 during 24h ; n=42 ) or normal saline ( n=44 ) . Postoperative analgesia included a single dose of intrapleural ropivacaine , intravenous paracetamol and nefopam , and patient‐controlled intravenous morphine . Vital parameters and analgesia were recorded during the 48 first postoperative hours . Seventy‐three patients were followed up . The patient 's chest was examined 1–2 weeks , 6 weeks and 4 months after surgery . At the last two observations , spontaneous pain score over a one‐week period ( visual analogue scale ) , neuropathic pain score ( NPSI ) , and intake of analgesics , were assessed . No drug affecting neuropathic pain ( except opiates ) was given during the follow‐up . Two patients in each group were lost to follow‐up after the 6 week visit . Ketamine improved immediate postoperative pain , but the groups were similar in terms of neuropathic pain and intake of analgesics , 6 weeks ( NPSI score : ketamine : 1.25 [ 0–4.125 ] ; placebo : 1 [ 0–4 ] ) and 4 months after surgery . Thus , ketamine given in 24‐h infusion failed to prevent chronic neuropathic pain after thoracotomy . Other perioperative preventive long‐lasting treatments or techniques could be tested in this context Several reports have suggested that preoperative nociceptive block may reduce postoperative pain , analgesic requirements , or both , beyond the anticipated duration of action of the analgesic agents . We have investigated , in a double-blind , placebo-controlled study , pre-emptive analgesia and the respiratory effects of preoperative administration of a multimodal antinociceptive regimen . Thirty patients undergoing thoracotomy were allocated r and omly to two groups . Before surgery , the treatment group ( n = 15 ) received morphine 0.15 mg kg-1 i.m . with perphenazine 0.03 mg kg-1 i.m . and a rectal suppository of indomethacin 100 mg , while the placebo group ( n = 15 ) received midazolam 0.05 mg kg-1 i.m . and a placebo rectal suppository . After induction of anaesthesia , the treatment group received intercostal nerve block with 0.5 % bupivacaine and adrenaline 1:200,000 ( 3 ml ) in the interspace of the incision and in the two spaces above and two spaces below . The placebo group received identical injections but with normal saline only . The treatment group consumed significantly less morphine by patient-controlled analgesia in the first 6 h after operation , but the total dose of morphine consumed on days 2 and 3 after surgery was significantly greater in the treatment group . There were no differences between the groups in postoperative VAS scores ( at rest or after movement ) , PaCO2 values or postoperative spirometry . However , pain thresholds to pressure applied at the side of the chest contralateral to the site of incision decreased significantly from preoperative values on days 1 and 2 after surgery in both groups . The results of this study do not support the preoperative use of this combined regimen for post-thoracotomy pain BACKGROUND We evaluated effects of thoracic epidural analgesia combined with intercostal nerve cryoanalgesia or epidural analgesia alone on acute and long-term pain after posterolateral thoracotomy . METHODS Forty-two elective thoracotomy patients were r and omly assigned to two groups , epidural combined with cryoanalgesia or epidural alone . A thoracic epidural catheter was inserted before induction of anesthesia . At the end of the operation , cryoanalgesia was performed to 3 intercostals nerves : 1 at the level of the incision , 1 caudal , and 1 cranial . Cryoanalgesia was blinded to the investigating anesthetists and patients . To avoid impingement of intercostal nerves , chest closure in all patients was performed using intracostal sutures through drilled holes in adjacent ribs . In the postanesthesia care unit , epidural infusion of ropivacaine ( 1 mg/mL ) with fentanyl ( 5 μg/mL ) was started and continued 3 days . Thereafter , pain was treated with oral strong or weak opioids combined with nonsteroidal antiinflammatory drugs or acetaminophen . Pain was assessed with the verbal pain scale or visual analog scale . Patients visited a local pain clinic at 8 weeks and at 6 months postoperatively . RESULTS The cryoanalgesia group had more neuropathic-type pain compared with the epidural-alone group 8 weeks after operation ( p < 0.05 ) . The cryoanalgesia group had also more pain on normal daily activities 8 weeks after the operation ( p < 0.05 ) . After 6 months , there were no statistically significant differences between groups . CONCLUSIONS Intercostal cryoanalgesia seems to increase the incidence of long-term pain after thoracotomy Introduction and hypothesisSpinal anaesthesia ( SA ) and general anaesthesia ( GA ) are widely used techniques for vaginal surgery for pelvic floor disorders with inconclusive evidence of the superiority of either . We conducted a r and omised controlled trial ( RCT ) to assess the feasibility of a full scale RCT aim ing to examine the effect of anaesthetic mode for vaginal surgery on operative , patient reported and length of hospital stay ( LOHS ) outcomes . Methods Patients undergoing vaginal surgery , recruited through a urogynaecology service in a University teaching hospital , were r and omised to receive either GA or SA . Patients were followed up for 12 weeks postoperatively . Pain was measured on a visual analogue scale ; nausea was assessed with a four-point verbal rating scale . Patient ’s subjective perception of treatment outcome , quality of life ( QoL ) and functional outcomes were assessed using the International Consultation on Incontinence Modular Question naire ( ICIQ ) on vaginal symptoms and the SF-36 question naire . Results Sixty women were r and omised , 29 to GA and 31 to SA . The groups were similar in terms of age and type of vaginal surgery performed . No statistically significant differences were noted between the groups with regard to pain , nausea , quality of life ( QoL ) , functional outcomes as well as length of stay in the postoperative recovery room , use of analgesia postoperatively and LOHS . Conclusion This study has demonstrated that a full RCT is feasible and should focus on the length of hospital stay in a subgroup of patients undergoing vaginal surgery where SA may help to facilitate enhanced recovery or day surgery OBJECTIVE To determine whether ropivacaine infiltration into all layers of the abdominal cesarean wound and spraying of the peritoneum decreases postoperative pain . METHODS A r and omized controlled trial of women undergoing cesarean delivery under general anesthetic allocated to receive either 30 mL of 0.75 % ropivacaine or 30 mL of saline into the wound , including spraying of the peritoneum . Postoperative pain and need for rescue opioids were assessed . RESULTS Of the 50 women in the ropivacaine group , 24 ( 48 % ) required pethidine or experienced severe pain within 1 hour postoperatively compared with 47 ( 94 % ) of 50 women in the control group ( relative risk 0.51 , 95 % CI , 0.38 - 0.69 ) . The amount of pethidine used in the first hour was reduced in the ropivacaine group ( mean difference -58 , 95 % CI , -73.53 to -42.40 ) . Use of diclofenac and tramadol/paracetamol was also reduced in the ropivacaine group . CONCLUSION Ropivacaine wound infiltration and peritoneal spraying during cesarean delivery under general anesthetic reduces severe pain and need for opioids OBJECTIVES To compare the effect of epidural and general anesthesia on the postoperative course and complication rate in patients undergoing radical prostatectomy . METHODS Ninety-eight men scheduled for radical retropubic prostatectomy ( RRP ) were r and omly assigned to receive epidural anesthesia only ( EA , n = 34 ) , combined epidural and general anesthesia ( EG , n = 33 ) or general anesthesia only ( GA , n = 31 ) . In the EA group , epidural anesthesia was induced and maintained with bupivacaine . In the EG group , patients received epidural bupivacaine after the induction of general anesthesia . In the GA group , anesthesia was induced with morphine and maintained with isoflurane . In the postoperative period , epidural patient-controlled analgesia ( PCA ) was maintained in all patients for 3 to 5 days . Patients were evaluated throughout the hospitalization period and at 3 , 6 , and 12 weeks following surgery . RESULTS The three groups did not differ with regard to postoperative pain , bleeding , urine output , fever , length of paralytic ileus , or length of hospitalization . No major cardiovascular , pulmonary , or neurologic complications occurred in any of the patients either perioperatively or in the first 3 months postoperatively . CONCLUSIONS Intraoperative anesthetic technique was not associated with a different postoperative complication rate in patients undergoing RRP . The very low incidence of complications and the uniform postoperative analgesic regimen may have contributed to the similarity between groups Due to unpleasant nature and physiological consequences of postoperative pain , search of safe and effective modalities for its management has remained a subject of interest to clinical research ers . Analgesic action of lidocaine infusion in patients with chronic neuropathic pain is well known but its place in relieving postoperative pain is yet to be established . The study aim ed to assess the effectiveness of perioperative intravenous lidocaine infusion on postoperative pain intensity and analgesic requirement . Sixty patients undergoing major upper abdominal surgery were recruited in this r and omized double blinded study . Thirty patients received lidocaine 2.0 % ( intravenous bolus 1.5 mg/kg followed by an infusion of 1.5 mg/kg/h ) , and 30 patients received normal saline according to r and omization . The infusion started 30 min before skin incision and stopped 1 h after the end of surgery . Postoperative pain intensity and analgesic ( diclofenac ) requirement were assessed at the interval 15 minutes for 1 hour then 4 hourly up to 24 hours . The pain intensity at rest and movement as well as the total postoperative analgesic ( diclofenac ) requirement were significantly lower ( 142.50 + /- 37.80 mg vs.185.00 + /- 41.31 mg , P<0.001 ) in lidocaine group . The extubation time was significantly longer in lidocaine group ( 14.43 + /- 3.50 minutes vs. 6.73 + /- 1.76 minutes , P<0.001 ) . The time for the first dose of analgesic requirement was longer in lidocaine group ( 60.97 + /- 18.05 minutes vs.15.73 + /- 7.46 minutes , P<0.001 ) . It can be concluded that perioperative infusion of low dose of lidocaine decreases the intensity of postoperative pain , reduces the postoperative analgesic consumption , without causing significant adverse effects in patients undergoing upper abdominal surgery Abstract Objective : To determine whether epidural analgesia during labour is associated with long term backache . Design : Follow up after r and omised controlled trial . Analysis by intention to treat Setting : Department of obstetrics and gynaecology at one NHS trust Participants : 369 women : 184 r and omised to epidural group ( treatment as allocated received by 123 ) and 185 r and omised to non-epidural group ( treatment as allocated received by 133 ) . In the follow up study 151 women were from the epidural group and 155 from the non-epidural group Main outcome measures : Self reported low back pain , disability , and limitation of movement assessed through one to one interviews with physiotherapist , question naire on back pain and disability , physical measurements of spinal mobility Results : There were no significant differences between groups in demographic details or other key characteristics . The mean time interval from delivery to interview was 26 months . There were no significant differences in the onset or duration of low back pain , with nearly a third of women in each group reporting pain in the week before interview . There were no differences in self reported measures of disability in activities of daily living and no significant differences in measurements of spinal mobility Conclusions : After childbirth there are no differences in the incidence of long term low back pain , disability , or movement restriction between women who receive epidural pain relief and women who receive other forms of pain Background : As a broader definition of preemptive analgesia , preventive analgesia aims to prevent the sensitization of central nervous system , hence the development of pathologic pain after tissular injury . To demonstrate benefits from preventive treatment , objective measurement of postoperative pain such as wound hyperalgesia and persistent pain should be evaluated . The current study assessed the role and timing of epidural analgesia in this context . Methods : In a r and omized , double-blinded trial , 85 patients scheduled to undergo neoplastic colonic resection were included . All the patients received a thoracic epidural catheter , systemic ketamine at a antihyperalgesic dose , and general anesthesia . Continuous infusion of analgesics belonging to the same class was administered by either intravenous or epidural route before incision until 72 h after surgery . Patients were allocated to four groups to receive intraoperative intravenous lidocaine – sufentanil – clonidine or epidural bupivacaine – sufentanil – clonidine followed postoperatively by either intravenous ( lidocaine – morphine – clonidine ) or epidural ( bupivacaine – sufentanil – clonidine ) patient-controlled analgesia . Postoperative pain scores ( visual analog scale ) , analgesic consumption , wound area of punctuate hyperalgesia , residual pain , and analgesics needed from 2 weeks until 12 months were recorded . Results : Analgesic requirements , visual analog scale scores , and area of hyperalgesia were significantly higher in the intravenous treatment group ( intravenous – intravenous ) , and more patients reported residual pain from 2 weeks until 1 yr ( 28 % ) . Although postoperative pain measurements did not differ , postoperative epidural treatment ( intravenous – epidural ) was less effective to prevent residual pain at 1 yr ( 11 % ; P = 0.2 with intravenous – intravenous group ) than intraoperative one ( epidural – epidural and epidural – intravenous groups ) ( 0 % ; P = 0.01 with intravenous – intravenous group ) . Conclusion : Combined with an antihyperalgesic dose of ketamine , intraoperative epidural analgesia provides effective preventive analgesia after major digestive surgery BACKGROUND : There is no widely recognized effective technique to optimally reduce pain scores and prevent persistent postoperative pain after nephrectomy . We compared continuous surgical site analgesia ( CSSA ) , epidural analgesia ( EA ) , and a control group ( patient-controlled analgesic morphine ) in patients undergoing open nephrectomy . METHODS : Sixty consecutive patients were r and omized to be part of EA , CSSA , or control groups postoperatively for 72 hours . All patients received patient-controlled analgesic morphine , if needed . Hyperalgesia was assessed on the first , second , and third postoperative days . Chronic pain characteristics and quality of life were analyzed at 1 and 3 months . The primary outcome was the pain score at 24 hours . Secondary outcomes were morphine consumption , postoperative rehabilitation , hyperalgesia , chronic pain incidence , and quality -of-life parameters . RESULTS : At 24 hours , mean ± st and ard deviation pain values at rest ( 2.4 ± 1.7 , 2.2 ± 1.2 , and 4.2 ± 1.2 , respectively , in EA , CSSA , and control groups , P < .001 ) and during coughing was lower in the EA and CSSA groups . Total morphine consumption was higher in the control group . Rehabilitation parameters improved sooner in the EA and CSSA groups . Median values of area of hyperalgesia differed at 48 hours between the EA group and the control group ( 36.4 cm2 ) and ( 52 cm2 ) ( P = .01 ) and at 72 hours among the EA group , CSSA group , and the control group ( 40 cm2 , 39.5 cm2 , and 59 cm2 , respectively ; P = .002 ) . CSSA reduced the severity of pain and hyperalgesia at 1 month and optimized quality of life 3 months after surgery ( role physical scores , P = .005 ) . CONCLUSIONS : CSSA and EA significantly improve postoperative analgesia , reduce postoperative morphine consumption , area of wound hyperalgesia , and accelerate patient rehabilitation after open nephrectomy . CSSA significantly reduces the severity of residual pain 1 month after surgery and optimizes quality -of-life parameters 3 months after surgery Objective . To determine whether health‐related quality of life ( HRQoL ) and postoperative recovery of women who undergo abdominal hysterectomy in a fast‐track program under general anesthesia ( GA ) differ from women who receive spinal anesthesia with intrathecal morphine ( SA ) . Design . Secondary analysis from an open r and omized controlled multicenter study . Setting . Five hospitals in south‐east Sweden . Population . One hundred and eighty women admitted for abdominal hysterectomy for benign disease were r and omized ; 162 completed the study , 80 with GA and 82 with SA . Methods . The HRQoL was measured preoperatively using the EuroQoL EQ‐5D and the Short‐Form‐36 health survey ( SF‐36 ) question naires . The EQ‐5D was used daily for 1 week ; thereafter , once weekly for 4 weeks and again 6 months after operation . The SF‐36 was completed at 5 weeks and 6 months . Date s of commencing and ending sick leave were registered . Main Outcome Measures . Changes in HRQoL ; duration of sick leave . Results . The HRQoL improved significantly faster in women after SA than after GA . Sick leave was significantly shorter after SA than after GA ( median 22.5 vs. 28 days ) . Recovery of HRQoL and duration of sick leave were negatively influenced by postoperative complications . In particular , the mental component of HRQoL was negatively affected by minor complications , even 6 months after the operation . Conclusions . Spinal anesthesia with intrathecal morphine provided substantial advantages in fast‐track abdominal hysterectomy for benign gynecological disorders by providing faster recovery and shorter sick leave compared with general anesthesia BACKGROUND Chronic postsurgical pain ( CPSP ) is a debilitating and costly condition . Risk factors for CPSP after autologous breast reconstruction have not been clearly established . Previously , we demonstrated that transversus abdominis plane ( TAP ) catheters delivering intermittent local anesthetic reduced postoperative morphine consumption . This prospect i ve follow-up study aim ed to ( 1 ) compare the incidence of CPSP after autologous breast reconstruction between patients who received postoperative intermittent TAP catheters with bupivacaine or saline boluses and ( 2 ) assess the factors that contribute to the development and maintenance of CPSP in this study cohort . METHODS Ninety-three patients who underwent deep inferior epigastric artery perforator or muscle-sparing transverse rectus abdominis breast reconstruction were r and omized to receive TAP catheters with bupivacaine or saline postoperatively . Subsequently , patients were followed for a year to assess persistent pain , pain severity , quality of life scores , and functional disability at 6 and 12 months after surgery . RESULTS Twenty-four percent and 23 % of patients reported CPSP at 6 and 12 months , respectively . There were no significant differences between groups ( bupivacaine vs. placebo ) on pain-related variables , including incidence of CPSP . Patients who reported greater variability in pain scores at rest over the first 48 hours postoperatively were more likely to have CPSP 6 months , but not 12 months , later . CONCLUSIONS Acute postoperative pain variability may contribute to the development of CPSP up to 6 months after autologous breast reconstruction surgery . Neither postoperative use of bupivacaine vs. saline in the TAP catheters nor acute pain severity influenced the 6- or 12-month incidence of CPSP CONTEXT Preemptive analgesia can decrease the sensitization of the central nervous system that would ordinarily amplify subsequent nociceptive input , but a clear demonstration of its clinical efficacy is necessary for it to become a routine component of acute pain therapy . OBJECTIVE To determine the impact of preemptive epidural analgesia on postoperative pain and other clinical ly important outcome variables after radical retropubic prostatectomy . DESIGN AND SETTING A block r and omized double-blind clinical trial lasting 20 months at a single academic medical center . PATIENTS A total of 100 generally healthy and neurologically intact patients scheduled for radical retropubic prostatectomy for the treatment of prostate cancer in whom an epidural catheter for treating postoperative pain was to be placed prior to the induction of general anesthesia . INTERVENTIONS Epidural bupivacaine , epidural fentanyl , or no epidural drug was administered prior to induction of anesthesia and throughout the entire operation , followed by aggressive postoperative epidural analgesia for all patients . MAIN OUTCOME MEASURES Daily pain scores during hospitalization and pain scores obtained 3.5 , 5.5 , and 9.5 weeks after hospital discharge . RESULTS The patients who received epidural fentanyl or bupivacaine prior to surgical incision ( preemptive analgesia ) experienced 33 % less pain while hospitalized ( P=.007 ) . Pain scores in those receiving preemptive analgesia were significantly lower at 9.5 weeks ( P=.02 ) , but were not significantly different at 3.5 or 5.5 weeks . At 9.5 weeks , 32 ( 86 % ) of 37 patients receiving preemptive analgesia were pain-free compared with 9 ( 47 % ) of 19 control patients ( P=.004 ) . Patients receiving preemptive analgesia were more active 3.5 weeks after surgery ( P=.01 ) , but not at 5.5 or 9.5 weeks . CONCLUSIONS Even in the presence of aggressive postoperative pain management , preemptive epidural analgesia significantly decreases postoperative pain during hospitalization and long after discharge , and is associated with increased activity levels after discharge Purpose We tested the hypothesis that the use of subarachnoid block ( SAB ) for vaginal hysterectomy produces superior postoperative analgesia and improves functional status at 12 weeks postoperatively . Methods In this r and omized controlled trial 89 patients received either st and ardized general anesthesia vs SAB with bupivacaine , clonidine , and morphine . Postoperatively , patients in both groups received multimodal pain management . Primary outcomes included evaluation of pain and functional status ( SF-36 Health Survey ) over the 12 postoperative weeks . Results Pain was well controlled throughout the study , as judged from the average pain numerical scale scores of ≤ 3 in both groups , at all times studied . Intrathecal analgesia lessened pain and decreased the use of morphine both in the postanesthesia care unit ( PACU ) and over the first 12 hr after discharge from the PACU ( P < 0.001 ) . Although patients who received SAB had a lower frequency of postoperative nausea in the PACU than the patients in the general anesthesia group ( P = 0.021 ) , this effect was not extended beyond the PACU stay . Subarachnoid block did not affect the length of hospitalization . At the two-week follow-up 69 % of patients in the SAB group and 48 % patients in the general anesthesia group were pain free ( P = 0.044 ) . At all evaluation intervals patients ’ functional status was comparable between the SAB and general anesthesia group . Conclusions A significantly better immediate postoperative analgesia was present in the SAB group , and the duration was consistent with the expected action of intrathecally administered drugs . Tw o weeks after surgery a higher percentage of the patients in the SAB group reported no pain . However , SAB had no effect on either length of hospitalization or patients ’ postoperative functional status . RésuméObjectifNous avons vérifié l’hypothèse voulant que l’usage d’un block sous-arachnoïdien ( BSA ) pour l’hystérectomie vaginale produise une analgésie postopératoire supérieure et améliore l’état fonctionnel jusqu’à 12 semaines après l’opération . MéthodeĽétude r and omisée et contrôlée a porté sur 89 patientes qui ont reçu une anesthésie générale normalisée ou un BSA avec de la bupivacaïne , de la clonidine et de la morphine . Après l’opération , toutes les patientes ont reçu un traitement de la douleur multimodal . La douleur et l’état fonctionnel ( SF-36 Health Survey ) ont été notés pendant 12 semaines postopératoires . RésultatsLa douleur a été bien contrôlée tout au long de l’étude , si l’on en juge par les scores moyens à l’échelle de douleur numérique ≤ 3 dans les deux groupes pour toutes les mesures prises . Ľanalgésie intrathécale a réduit la douleur et diminué l’usage de morphine à la salle de réveil ( SDR ) et pendant les 12 premières heures après le départ de la SDR ( P < 0,001 ) . Les patientes du groupe BSA ont eu moins de nausées postopératoires en SDR que les patientes sous anesthésie générale ( AG ) , ( P = 0,021 ) , mais cet effet ne s’est pas prolongé au delà du séjour en SDR . Le BSA n’a pas permis d’écourter l’hospitalisation . Lors de l’examen de contrôle à la deuxième semaine , 69 % des patientes du groupe BSA et 48 % du groupe d’AG n’avaient plus de douleur ( P= 0,044 ) . Pendant toute l’étude , l’état fonctionnel a été comparable entre les groupes . Conclusion Une analgésie postopératoire immédiate significativement meilleure a été notée avec le BSA et de durée conforme à l’action attendue des médicaments intrathécaux administrés . Deux semaines après l’opération , un plus fort pourcentage de patientes du groupe BSA était sans douleur . Le BSA n’a cependant pas modifié la durée de l’hospitalisation ou l’état fonctionnel postopératoire des patientes Objectives Cesarean delivery is a common surgical procedure with anticipated substantial postoperative pain . The addition of a transversus abdominis plane block ( TAPB ) to a multimodal analgesic regimen that includes intrathecal morphine may provide improved early pain outcomes and decrease the risk of chronic post-surgical pain . The purpose of this research was to assess the ability of an ultrasound-guided TAPB with low-dose ropivacaine to decrease early postoperative pain , opioid consumption , and risk of developing persistent pain when compared with a placebo block . Methods Eighty-three women were r and omly assigned to either a treatment ( 0.25 % ropivacaine ) or control group ( 0.9 % saline ) in this double-blind trial , and 74 women were included in the final analysis . Ultrasound-guided TAPBs were performed with an injection of 20 mL of study solution per side . The primary outcome measures of this study were : pain at rest and pain after movement measured with a numeric rating scale , results of the Quality of Recovery-40 ( QoR-40 ) question naire , and opioid consumption at 24 hr . These were used with an a priori sample size calculation to detect a 30 % reduction in pain scores , a 10 % improvement in QoR-40 score , and a 50 % reduction in opioid consumption . Health quality and physical functioning were assessed using the Short Form 36 ( SF-36 ® ) Health Survey at 30 days and six months . Results Assessment at 24 hr after Cesarean delivery revealed no clinical ly important differences between groups in postoperative pain , QoR-40 , or opioid consumption . There were no clinical ly important differences between groups regarding measures of nausea , pruritus , vomiting , urine retention ( 2 , 24 , and 48 hr postoperatively ) , 24-hr QoR-40 sub-dimensions , or the SF-36 Health Survey ( 30 days and six months postoperatively ) . Conclusions Ultrasound-guided TAPB did not improve postoperative pain , quality of recovery , or opioid consumption 24 hr following surgery . Similar health and functioning ( SF-36 ) at 30 days and six months were reported by both groups . This trial was registered at Clinical Trials.gov number : NCT01261637.RésuméObjectifsL’accouchement par césarienne est une procédure chirurgicale courante ou l’on anticipe une importante douleur postopératoire . L’ajout d’un bloc dans le plan du muscle transverse de l’abdomen ( TAP ) à un protocol e antalgique multimodal incluant la morphine intrathécale pourrait améliorer les douleurs précoces et diminuer le risque de douleur postopératoire chronique . L’objectif de cette étude était d’évaluer la capacité d’une TAP guidée par échographie , utilisant une faible dose de ropivacaïne , à diminuer la douleur postopératoire précoce , la consommation de morphinique et le risque de développement de douleur persistante comparativement à un bloc avec un placebo . MéthodesQuatre-vingts-trois femmes ont été r and omisées dans le groupe de traitement ( ropivacaïne 0,25 % ) ou dans le groupe témoin ( sérum physiologique 0,9 % ) dans une étude à double insu et 74 femmes ont été incluses dans l’analyse définitive . Les TAPB guidées par échographie ont été pratiquées par injection de 20 mL de la solution étudiée de chaque côté . Les critères d’évaluation principaux de cette étude étaient les suivants : douleur au repos et douleur après mouvement mesurées avec une échelle d’évaluation numérique , les résultats du question naire de la Qualité de la convalescence-40 ( QoR-40 ) et la consommation de morphinique à 24 h. Ces critères ont été utilisés avec un calcul de taille d’échantillon a priori conçu pour détecter une réduction de 30 % des scores de douleur , une amélioration de 10 % du score du QoR-40 et une baisse de 50 % de la consommation de morphinique . La qualité de la santé et le fonctionnement physique ont été évalués à l’aide d’une enquête de santé avec le Formulaire abrégé 36 ( SF-36 ® ) à 30 jours et six mois . RésultatsL’évaluation effectuée 24 heures après l’accouchement par césarienne n’a révélé aucune différence cliniquement importante entre les groupes pour la douleur postopératoire , le QoR-40 ou la consommation de morphinique . Il n’y a pas eu de différence cliniquement importante entre les groupes concernant les mesures de nausées , prurit , vomissements , rétention d’urine ( à 2 h , 24 h et 48 h postopératoires ) , QoR-40 à 24 h ou de l’enquête de santé avec le Formulaire abrégé 36 ( 30 jours et 6 mois postopératoires ) . Conclusions La TAP guidée par échographie n’a pas amélioré la douleur postopératoire , la qualité de la convalescence ou la consommation de morphinique 24 h après l’intervention chirurgicale . Des scores similaires de santé et de fonctionnement ( SF-36 ) ont été décrits dans les deux groupes à 30 jours et 6 mois . Cette étude a été enregistrée sur le site www . clinical trials.gov : NCT01261637 Abstract Background The effect of the systemic lidocaine on postoperative recovery has not been definitively investigated despite its analgesic efficacy after surgery . The aim of this r and omized , double-blinded , controlled study was to evaluate the effect of intravenously administered lidocaine on the quality of recovery and on acute and chronic postoperative pain after robot-assisted thyroidectomy . Methods Ninety patients who were undergoing robotic thyroidectomy were r and omly assigned to the lidocaine or the control groups . The patients received 2 mg/kg of lidocaine followed by continuous infusions of 3 mg/kg/h of lidocaine ( Group L ) or the same volume of 0.9 % normal saline ( Group C ) intravenously during anesthesia . The acute pain profiles and the quality of recovery , which was assessed using the quality of recovery-40 question naire ( QoR-40 ) , were evaluated for 2 days postoperatively . Chronic postsurgical pain ( CPSP ) and sensory disturbances at the surgical sites were evaluated 3 months after surgery . Results The QoR-40 and pain scores that were assessed during the 2 days that followed surgery were largely comparable between the groups . However , CPSP was more prevalent in the Group C than in the Group L ( 16/43 vs. 6/41 ; p = 0.025 ) . The tactile sensory score 3 months after the operation was significantly greater in the Group L than in the Group C ( 7 vs. 5 ; p = 0.001 ) . ConclusionS ystemic lidocaine administration was associated with reductions in CPSP and sensory impairment after robot-assisted thyroidectomy although it was not able to reduce acute postsurgical pain or improve the quality of recovery . Trial registry number NCT01907997 ( http:// clinical trials.gov ) Objectives : Breast cancer surgery is associated with a high incidence of persistent postsurgical pain ( PPSP ) . The aim of this study was to evaluate the impact of intravenous ( IV ) lidocaine on acute and PPSP , analgesic requirements , and sensation abnormalities in patients undergoing surgery for breast cancer . Methods : Thirty-six patients participated in this r and omized , double-blinded study . Before induction of general anesthesia , patients received a bolus of intravenous lidocaine 1.5 mg/kg followed by a continuous infusion of lidocaine 1.5 mg/kgh ( lidocaine group ) or an equal volume of saline ( control group ) . The infusion was stopped 1 hour after the skin closure . Pain scores and analgesic consumption were recorded at 2 , 4 , 24 hours , and then daily for 1 week postoperatively . Three months later , patients were assessed for PPSP and secondary hyperalgesia . Results : Two ( 11.8 % ) patients in the lidocaine group and 9 ( 47.4 % ) patients in the control group reported PPSP at 3 months follow-up ( P=0.031 ) . McGill Pain Question naire revealed greater present pain intensity-visual analog scale in the control group ( 14.6±22.5 vs. 2.6±7.5 ; P=0.025 ) . Secondary hyperalgesia ( area of hyperalgesia/length of surgical incision ) was significantly less in the lidocaine group compared with control group ( 0.2±0.8 vs. 3.2±4.5 cm ; P=0.002 ) . The 2 groups were similar in terms of analgesic consumption during the early postoperative period . Discussion : Intravenous perioperative lidocaine decreases the incidence and severity of PPSP after breast cancer surgery . Prevention of the induction of central hyperalgesia is a potential mechanism Phantom limb pain may appear in up to 85 % of patients after amputation . There is no effective treatment . Perioperative epidural infusion of morphine and bupivacaine , alone or in combination , is effective in preventing phantom limb pain in patients with pre-existing limb pain . Serious side-effects , however , make them difficult to manage on a general ward . Clonidine has been shown to be an effective postoperative analgesia when applied epidurally . To mitigate the potentially serious side-effects of all these drugs , we have studied their combined efficiency in preventing phantom limb pain in a prospect i ve controlled study of 24 patients undergoing lower limb amputation . In the study group ( n = 13 ) , an epidural infusion containing bupivacaine 75 mg , clonidine 150 micrograms and diamorphine 5 mg in 60 ml normal saline was given at 1 - 4 ml/h 24 - 48 h preoperatively and maintained for at least 3 days postoperatively . The control group ( n = 11 ) received on-dem and opioid analgesia . Pain was assessed by visual analogue scale at 7 days , 6 months and 1 year . At 1 year follow-up , one patient in the study group and eight patients in the control group had phantom pain ( P < 0.002 ) and two patients in the study group versus eight patients in the control group had phantom limb sensation ( P < 0.05 ) . There was no significant improvement in stump pain . We conclude that perioperative epidural infusion of diamorphine , clonidine and bupivacaine is safe and effective in reducing the incidence of phantom pain after amputation BACKGROUND Postoperative analgesia of iliac crest ( IC ) donor site can be performed by on site infiltrations of local anesthetics ( LA ) or morphine . Single injections or continuous infusions of LA proved their efficacy in adults , but was not reported in children . We prospect ively evaluated the interest of a continuous infusion of 0.2 % ropivacaïne at the IC donor site in terms of postoperative pain relief and rescue analgesics consumption . METHODS Sixteen consecutive patients , aged from 4 to 16 years scheduled for maxillar alveolar graft with IC bone , were included . After IC bone graft surgery under general anesthesia , they received a 0.2 - 0.4 ml x kg(-1 ) bolus of 0.2 % ropivacaïne through the IC catheter ; then a continuous infusion of 0.2 % ropivacaïne at 0.125 ml x kg(-1 ) x h(-1 ) was administrated for 48 h with disposable elastomeric pumps . Children systematic ally received paracetamol ( 15 mg x kg(-1 ) four times a day ) and niflumic acid ( 40 mg x kg(-1 ) twice a day ) . Postoperative pain was evaluated using a Visual Analog Scale ( > 7 years old ) or Children and Infants Postoperative Pain Score ( between 4 and 7 years old ) every 4 h until H48 . Doses of rescue analgesics and adverse events ( LA toxicity , catheter 's removal , nausea-vomiting ) were also noted . Three months after surgery a blinded clinical research assistant review ed all children and assessed functional recovery , neuropathic chronic pain symptoms or local complications . RESULTS The median value of IC graft pain scores was 0 during whole studied period . Of the patients , 31.2 % did not require any rescue analgesics and 43.8 % needed only once . No adverse events related to LA and no removal of catheter were noted . One child had nausea in the 48-h postoperative period , and one child had neuropathic pain symptoms at 3 months at the donor site . CONCLUSION Continuous infusion of 0.2 % ropivacaïne through an IC catheter is an optimal and safe technique of regional postoperative analgesia after bone graft harvest in children Background : The efficacy of local anesthetic wound infiltration for the treatment of acute and chronic postoperative pain is controversial and there are no detailed studies . The primary objective of this study was to evaluate the influence of ropivacaine wound infiltration on chronic pain after breast surgery . Methods : In this prospect i ve , r and omized , double-blind , parallel-group , placebo-controlled study , 236 patients scheduled for breast cancer surgery were r and omized ( 1:1 ) to receive ropivacaine or placebo infiltration of the wound , the second and third intercostal spaces and the humeral insertion of major pectoralis . Acute pain , analgesic consumption , nausea and vomiting were assessed every 30 min for 2 h in the postanesthesia care unit and every 6 h for 48 h. Chronic pain was evaluated 3 months , 6 months , and 1 yr after surgery by the brief pain inventory , hospital anxiety and depression , and neuropathic pain question naires . Results : Ropivacaine wound infiltration significantly decreased immediate postoperative pain for the first 90 min , but did not decrease chronic pain at 3 months ( primary endpoint ) , or at 6 and 12 months postoperatively . At 3 months , the incidence of chronic pain was 33 % and 27 % ( P = 0.37 ) in the ropivacaine and placebo groups , respectively . During follow-up , brief pain inventory , neuropathic pain , and anxiety increased over time in both groups ( P < 0.001 ) while depression remained stable . No complications occurred . Conclusion : This multicenter , prospect i ve study shows that ropivacaine wound infiltration after breast cancer surgery decreased immediate postoperative pain but did not decrease chronic pain at 3 , 6 , and 12 months postoperatively OBJECTIVE We assessed in a r and omized study the feasibility and efficacy of awake video-assisted thoracoscopic bullectomy with pleural abrasion to treat spontaneous pneumothorax . METHODS Between January 2001 and June 2005 , a total of 43 patients with primary spontaneous pneumothorax were r and omly assigned by computer to undergo video-assisted thoracoscopic bullectomy and pleural abrasion under sole thoracic epidural anesthesia or general anesthesia with single-lung ventilation ( control group ) . Primary outcome measures included technical feasibility and patient satisfaction with anesthesia as scored into 4 grade s ( from 1 , unsatisfactory , to 4 , excellent ) . Secondary outcome measures included global operating room time , assessment of thoracic pain by visual analog pain scale , number of nursing care calls , hospital stay , and recurrences within 12 months . RESULTS In the awake group , technical feasibility was scored as excellent , good , and satisfactory in 8 , 7 , and 6 patients , respectively . Intergroup comparisons ( awake versus control ) showed that global operating room time ( 78.0 + /- 20.0 vs 105.0 + /- 15.0 minutes , P < .0001 ) , perioperative visual analog pain scale score ( 2.0 + /- 3.0 vs 3.5 + /- 2.0 , P = .005 ) , nursing care calls ( 2.0 + /- 1 vs 3.0 + /- 3.0 , P = .017 ) , hospital stay ( 2.0 + /- 1.0 days vs 3.0 + /- 1.0 days , P < .0001 ) , and overall costs ( 2540 euros + /- 352 euros vs 3550 euros + /- 435 euros , P < .0001 ) were significantly better in the awake group . In the awake group , 5 patients ( 23.8 % ) could be discharged within the first 24 postoperative hours . One patient in the awake group and 2 patients in the control group had recurrences within 12 months ( difference not significant ) . CONCLUSION In our study , awake video-assisted thoracoscopic bullectomy with pleural abrasion proved easily feasible and result ed in shorter hospital stays and reduced procedure-related costs while providing equivalent outcome to procedures performed under general anesthesia Background : Recently , there has been increasing interest in the use of analgesic adjuncts such as intravenous ( IV ) ketamine and lidocaine . Objectives : To compare the effects of perioperative IV lidocaine and ketamine on morphine requirements , pain scores , quality of recovery , and chronic pain after open nephrectomy . Study Design : A prospect i ve , r and omized , placebo-controlled , double-blind trial . Setting s : The study was conducted in Charles Nicolle University Hospital of Tunis . Methods : Sixty patients were r and omly allocated to receive IV lidocaine : bolus of 1.5 mg/kg at the induction of anesthesia followed by infusion of 1 mg/kg/h intraoperatively and for 24 h postoperatively or ketamine : bolus of 0.15 mg/kg followed by infusion of 0.1 mg/kg/h intraoperatively and for 24 h postoperatively or an equal volume of saline ( control group [ CG ] ) . Measurements : Morphine consumption , visual analog scale pain scores , time to the first passage of flatus and feces , postoperative nausea and vomiting ( PONV ) , 6-min walk distance ( 6MWD ) at discharge , and the incidence of chronic neuropathic pain using the “ Neuropathic Pain Question naire ” at 3 months . Results : Ketamine and lidocaine reduced significantly morphine consumption ( by about 33 % and 42 % , respectively ) and pain scores compared with the CG ( P < 0.001 ) . Lidocaine and ketamine also significantly improved bowel function in comparison to the CG ( P < 0.001 ) . Ketamine failed to reduce the incidence of PONV . The 6 MWD increased significantly from a mean ± st and ard deviation of 27 ± 16.2 m in the CG to 82.3 ± 28 m in the lidocaine group ( P < 0.001 ) . Lidocaine , but not ketamine , reduced significantly the development of neuropathic pain at 3 months ( P < 0.05 ) . Conclusion : Ketamine and lidocaine are safe and effective adjuvants to decrease opioid consumption and control early pain . We also suggest that lidocaine infusion serves as an interesting alternative to improve the functional walking capacity and prevent chronic neuropathic pain at 3 months after open nephrectomy PURPOSE We assess pain and quality of life following radical retropubic prostatectomy and determine whether intraoperative anesthetic management has any long-term effects on outcomes . MATERIAL S AND METHODS A total of 110 patients undergoing radical retropubic prostatectomy were r and omly assigned to receive epidural and /or general anesthesia . Patients responded to a question naire mailed 3 and 6 months following surgery that assessed prostate symptoms , pain related to surgery , quality of life and mood . RESULTS No long-term effects of anesthesia were observed . Of the 103 respondents ( 94 % ) at 3 months 49 % had some pain related to surgery . Although pain was not related to anesthesic technique , patients who had it at 3 months used significantly more pain medication on postoperative day 3 . Pain at 3 months was mild , averaging 1.5 on a scale of 0 to 10 , and associated with poor perceptions of overall health ( p < 0.02 ) , and reduced physical ( p < 0.01 ) and social ( p < 0.01 ) functioning . Pain at 3 months was associated with higher levels of preoperative anxiety ( p < 0.05 ) . At 6 months 36 of 90 patients ( 35 % ) had some pain related to surgery and the impact was similar . CONCLUSIONS Long-term effects of intraoperative anesthesic technique were not apparent . Mild pain following radical retropubic prostatectomy was common and associated with reduced quality of life , particularly social functioning . Affective distress , particularly anxiety , before surgery and use of pain medications following surgery may be predictors of chronic pain following radical retropubic prostatectomy We performed a prospect i ve , r and omized clinical trial to determine whether continuous infusion of bupivacaine hydrochloride decreased the use of narcotics for the relief of pain after an amputation . Twenty-one patients who were to have an amputation of the lower extremity because of ischemic necrosis secondary to peripheral vascular disease were divided into two groups with use of a table of r and om numbers . Group A ( the treatment group ) included nine patients who were to have a transtibial amputation , one patient who was to have a disarticulation at the knee , and one patient who was to have a transfemoral amputation . Group B ( the control group ) included seven patients , two patients , and one patient , respectively . After the amputation had been performed , a Teflon catheter was placed adjacent to the transected end of the sciatic or posterior tibial nerve . Postoperatively , the patients received continuous infusion of either bupivacaine ( Group A ) or normal saline solution ( Group B ) for seventy-two hours . Intravenous administration of morphine with use of a patient-controlled pump also was permitted during this period . The amount of morphine that was used was recorded meticulously . The patients in Group A used less morphine during the first and second days after the operation than did those in Group B. There was no difference between the groups with regard to the amount of morphine used on the third postoperative day . Over-all , eleven of fourteen patients who completed question naires reported a decrease in pain between the three and six-month evaluations . We concluded that continuous perineural infusion of an anesthetic appears to be a safe , effective method for the relief of postoperative pain but that it does not prevent residual or phantom-limb pain in patients who have had an amputation of the lower extremity because of ischemic changes secondary to peripheral vascular disease Background : Postoperative pain after radical retropubic prostatectomy can be severe unless adequately treated . Low thoracic epidural analgesia and patient-controlled intravenous analgesia were compared in this double-blind , r and omized study . Methods : Sixty patients were r and omly assigned to receive either low thoracic epidural analgesia ( group E ) or patient-controlled intravenous analgesia ( group P ) for postoperative pain relief . All patients had general anesthesia combined with thoracic epidural analgesia during the operation . Postoperatively , patients in group E received an infusion of 1 mg/ml ropivacaine , 2 & mgr;g/ml fentanyl , and 2 & mgr;g/ml adrenaline , 10 ml/h during 48 h epidurally , and a placebo patient-controlled intravenous analgesia pump intravenously . Patients in group P received a patient-controlled intravenous analgesia pump with morphine intravenously and 10 ml/h placebo epidurally . Pain , the primary outcome variable , was measured using the numeric rating scale at rest ( incision pain and “ deep ” visceral pain ) and on coughing . Secondary outcome variables included gastrointestinal function , respiratory function , mobilization , and full recovery . Health-related quality of life was measured using the Short Form-36 question naire , and plasma concentration of fentanyl was measured in five patients to exclude a systemic effect of fentanyl . Results : Incisional pain and pain on coughing were lower in group E compared with group P at 2–24 h , as was deep pain between 3 and 24 h postoperatively ( P < 0.05 ) . Maximum expiratory pressure was greater in group E at 4 and 24 h ( P < 0.05 ) compared with group P. No difference in time to home discharge was found between the groups . The mean plasma fentanyl concentration varied from 0.2 to 0.3 ng/ml during 0–48 h postoperatively . At 1 month , the scores on emotional role , physical functioning , and general health of the Short Form-36 were higher in group E compared with group P. However , no group × time interaction was found in the Short Form-36 . Conclusions : The authors found evidence for better pain relief and improved expiratory muscle function in patients receiving low thoracic epidural analgesia compared with patient-controlled analgesia for radical retropubic prostatectomy . Low thoracic epidural analgesia can be recommended as a good method for postoperative analgesia after abdominal surgery Background Following publication of the PRISMA statement , the UK Centre for Review s and Dissemination ( CRD ) at the University of York in Engl and began to develop an international prospect i ve register of systematic review s with health-related outcomes . The objectives were to reduce unplanned duplication of review s and provide transparency in the review process , with the aim of minimizing reporting bias . Methods An international advisory group was formed and a consultation undertaken to establish the key items necessary for inclusion in the register and to gather views on various aspects of functionality . This article describes the development of the register , now called PROSPERO , and the process of registration . Results PROSPERO offers free registration and free public access to a unique prospect i ve register of systematic review s across all areas of health from all around the world . The dedicated web-based interface is electronically search able and available to all prospect i ve registrants . At the moment , inclusion in PROSPERO is restricted to systematic review s of the effects of interventions and strategies to prevent , diagnose , treat , and monitor health conditions , for which there is a health-related outcome .Ideally , registration should take place before the research ers have started formal screening against inclusion criteria but review s are eligible as long as they have not progressed beyond the point of completing data extraction .The required data set captures the key attributes of review design as well as the administrative details necessary for registration .Su bmi tted registration forms are checked against the scope for inclusion in PROSPERO and for clarity of content before being made publicly available on the register , rejected , or returned to the applicant for clarification . The public records include an audit trail of major changes to planned methods , details of when the review has been completed , and links to result ing publications when provided by the authors . Conclusions There has been international support and an enthusiastic response to the principle of prospect i ve registration of protocol s for systematic review s and to the development of PROSPERO .In October 2011 , PROSPERO contained 200 records of systematic review s being undertaken in 26 countries around the world on a diverse range of interventions OBJECTIVE This prospect i ve r and omized double-blind study examined the effect of local wound infusion of anesthetics on pain control in the thoracotomy wound of patients undergoing minimally invasive cardiac surgery . METHODS Patients who underwent coronary artery bypass grafting or cardiac valvular procedures via a minimally invasive thoracotomy were studied . Patients were enrolled and r and omly allocated to two groups with different modalities of postoperative analgesia . The thoracotomy wound infusion group received 0.15 % bupivacaine infused continuously at 2 mL/h through a catheter embedded in the wound , as well as intravenous patient-controlled analgesia . The control group had patient-controlled analgesia alone with a sham thoracotomy wound infusion of normal saline . Verbal analog pain scores ( 0 - 10 points ) and recovery profiles were investigated . RESULTS There were 19 patients in each group for complete data analysis . On the first day after the operation , infusion of local anesthetics significantly reduced the verbal analog pain scores both at rest and during motion ( thoracotomy wound infusion vs control ) . The improved pain relief with thoracotomy wound infusion persisted at day 3 and even at 3 months after the operation . No difference was noted about time to extubation , length of intensive care unit stay , or hospital stay . CONCLUSION In this controlled double-blind study , thoracotomy wound infusion and patient-controlled analgesia were superior to patient-controlled analgesia alone in reducing pain at 1 , 3 , and 90 days after minimally invasive cardiac surgery BACKGROUND High thoracic epidural analgesia ( HTEA ) has been shown to reduce psychological morbidity in the early period following coronary artery bypass graft surgery ( CABG ) . Our aim was to identify whether the effect persists in the longer term . MATERIAL S AND METHODS Patients from a previous r and omised study of HTEA for CABG were followed up 6 months to 3 years following surgery . The cardiac depression scale ( CDS ) was used to identify severity of depression . RESULTS Sixty-one of the original 78 patients were able to participate in the study . Eight point three percent of patients had CDS scores > 100 , consistent with severe depression ( 1 epidural patient , 4 control patients , P=0.353 ) . After adjustment for time of follow-up , the CDS scores in patients who received HTEA were significantly lower ( 66+/-3.5 ) than patients who received intravenous morphine analgesia ( 79+/-3.5 ) P<0.05 CONCLUSION The use of HTEA results in a lower risk of depression 6 months or more following CABG We investigated the analgesic effect of regional application of bupivacaine and a morphine-bupivacaine combination on iliac crest donor-site pain in a r and omized , double-blind controlled study of 45 patients . Patients were divided into three groups : group I ( control group ) , group II ( bupivacaine ) and group III ( morphine-bupivacaine combination ) . Pain in the acute stage was evaluated by visual analogue scale scoring and analgesic consumption . Chronic pain and dysesthesia were evaluated at 12 weeks after operation at a follow-up visit . It was found that local bupivacaine administration with or without morphine provided satisfactory analgesia in the acute stage following iliac crest bone harvesting . The amount of analgesic consumption was found to be significantly less with the addition of morphine to bupivacaine , when compared to bupivacaine alone . Effective pain control in the acute stage had a favorable effect on long-term pain and dysesthesia , which are the main complaints after iliac crest bone harvesting . This effect was augmented significantly by addition of morphine to the local anesthetic solution OBJECTIVE The research ers sought to assess whether the widely used 1994 Cochrane Highly Sensitive Search Strategy ( HSSS ) for r and omized controlled trials ( RCTs ) in MEDLINE could be improved in terms of sensitivity , precision , or parsimony . METHODS A gold st and ard of 1,347 RCT records and a comparison group of 2,400 non-trials were r and omly selected from MEDLINE . Terms occurring in at least 1 % of RCT records were identified . Fifty percent of the RCT and comparison group records were r and omly selected , and the ability of the terms to discriminate RCTs from non-trial records was determined using logistic regression . The best performing combinations of terms were tested on the remaining records and in MEDLINE . RESULTS The best discriminating term was " Clinical Trial " ( Publication Type ) . In years where the Cochrane assessment of MEDLINE records had taken place , the strategies identified few additional unindexed records of trials . In years where Cochrane assessment has yet to take place , " R and omized Controlled Trial " ( Publication Type ) proved highly sensitive and precise . Adding six more search terms identified further , unindexed trials at reasonable levels of precision and with sensitivity almost equal to the Cochrane HSSS . CONCLUSIONS Most reports of RCTs in MEDLINE can now be identified easily using " R and omized Controlled Trial " ( Publication Type ) . More sensitive search es can be achieved by a brief strategy , the Centre for Review s and Dissemination/Cochrane Highly Sensitive Search Strategy ( 2005 revision ) Purpose To find the effect of pre-peritoneal instillation of bupivacaine on ‘ dissectalgia ’ ( pain over a wide area corresponding to the area of pre-peritoneal dissection ) and return to work following totally extraperitoneal ( TEP ) repair for groin hernia in labor-active males . Methods Fifty-three consecutive ASA grade I adult males undergoing TEP for groin hernia were r and omized to control group A ( n = 28 ) and test group B ( n = 25 ) , receiving 30 ml saline or 0.25 % bupivacaine pre-peritoneally after placing mesh , respectively . Assessment parameters included time ( h ) to rescue analgesia , number of patients needing additional injectable analgesia at night during their hospital stay , visual analog scale ( VAS ) score for pain at 24 h , 48 h , and then weekly for 4 weeks , and time of resuming their job . Results The time to rescue analgesia was significantly shorter in group A ( 4.50 ± 2.3 ) than in group B ( 7.00 ± 4.1 ) , P = 0.0077 . A significantly greater number of group A patients needed additional injectable analgesia at bed time than group B patients ( 24 vs. 6 , respectively , P < 0.0001 on the first night ; 11 vs. 2 , respectively , P = 0.008 on the second night ) . The VAS scores were significantly higher in group A patients than group B patients ( 3.47 ± 1.04 vs. 1.69 ± 1.04 , respectively , at 24 h postoperatively , P < 0.0001 ; 2.29 ± 1.44 vs. 1.36 ± 0.81 , respectively , at 48 h postoperatively , P = 0.0063 ) . However , subsequent VAS scores up to 4 weeks postoperatively were comparable , as was the time of resuming their job . No patient had seroma/fluid collection , chronic pain , or recurrence , with the minimum follow-up being 3 years . Conclusions Dissectalgia following TEP deserves its due recognition . Pre-peritoneal bupivacaine instillation significantly reduces its occurrence , although the time of patient ’s resuming their jobs remains unaffected In this study , we compared the effects of two analgesic regimens on perioperative nitric oxide index ( NOx ) and the likelihood of subsequent development of chronic postsurgical pain ( CPSP ) after breast surgery and sought to determine the association among early postoperative pain , NOx , and the likelihood of subsequent development of CPSP . Twenty-nine consecutive ASA I or II patients undergoing breast surgery with axillary clearance were r and omly allocated to one of two groups . Patients in group S ( n = 15 ) received a st and ard intraoperative and postoperative analgesic regimen ( morphine sulfate , diclofenac , dextropropoxyphene hydrochloride + acetaminophen prn ) . Patients in group N ( n = 14 ) received a continuous paravertebral block ( for 48 h ) and acetaminophen and parecoxib ( followed by celecoxib up to 5 days ) . Visual analog scale pain scores at rest and on arm movement were recorded regularly until the fifth postoperative day . A telephone interview was conducted 10 wk postoperatively . The McGill Pain Question naire was used to characterize pain . NOx was estimated preoperatively , at the end of surgery , 30 min and 2 , 4 , 12 , 24 , 48 h postoperatively . Twelve ( 80 % ) patients in group S and no patient in group N developed CPSP ( P = 0.009 ) . Compared with patients with a pain rating index ≥1 ( n = 18 ) 10 wk postoperatively , patients with a pain rating index = 0 ( n = 11 ) had lesser visual analog scale pain scores on movement at each postoperative time point from 30 min until 96 h postoperatively ( P < 0.005 ) and at rest 30 min ( 0.6 ± 1.5 versus 30.2 ± 26.8 ; P = 0.004 ) , 4 h ( 2.3 ± 7.5 versus 19.0 ± 25.8 ; P = 0.013 ) , 8 h ( 4.4 ± 10.2 versus 21.4 ± 27.0 ; P = 0.03 ) and 12 h ( 0.7 ± 1.2 versus 15.4 ± 27.0 ; P = 0.035 ) postoperatively . NOx values were greater in group N compared with group S 48 h postoperatively ( 40.6 ± 20.1 versus 26.4 ± 13.5 ; P = 0.04 ) Background The incidence , etiology , and evolution of complications after interscalene brachial plexus block ( ISB ) are not well-known . The authors prospect ively monitored 521 patients for complications during the first 9 months after ISB . Methods A total of 521 adults scheduled for elective shoulder surgery performed with an ISB were included in this prospect i ve study . The ISB procedure was st and ardized for all patients . Acute complications were recorded . Patients were observed daily ( for 10 days ) for paresthesias , dysesthesias , pain not related to surgery , and muscular weakness and were evaluated at 1 , 3 , 6 , and 9 months after surgery . Persistence of paresthesias , dysesthesias , pain not related to surgery , or muscular weakness was investigated at 1 or 3 months by means of electroneuromyography . Final evaluation was performed at 9 months . Results A total of 520 patients completed the study ; one was excluded after surgical axillary nerve damage . Two hundred thirty-four patients had an interscalene catheter . Acute complications consisted of one pneumothorax ( 0.2 % ) and one episode of central nervous system toxicity ( incoherent speech ; 0.2 % ) . At 10 days , 74 patients ( 14 % ) were symptomatic , and none had muscular weakness . At 1 month , 41 patients ( 7.9 % ) had symptoms , and none had muscular weakness . Thirty patients underwent electroneuromyography ; sulcus ulnaris syndrome ( n = 8) , carpal tunnel syndrome ( n = 2 ) , and complex regional pain syndrome ( n = 1 ) were diagnosed . At 3 months 20 patients ( 3.9 % ) were symptomatic , and none had muscular weakness . All underwent electroneuromyography ; carpal tunnel syndrome ( n = 2 ) , complex regional pain syndrome ( n = 4 ) , plexus neuropathy ( n = 1 ) , and plexus damage ( n = 1 ) were diagnosed . At 6 months , 5 patients ( 0.9 % ) were symptomatic . At 9 months , 1 patient ( 0.2 % ) had persistence of dysesthesia . Conclusions Interscalene brachial plexus block performed with a st and ardized technical approach , material , and drugs is associated with an incidence of short- and severe long-term complications of 0.4 % . In case of persistent paresthesia , dysesthesia , or pain not related to surgery after ISB , sulcus ulnaris syndrome , carpal tunnel syndrome , or complex regional pain syndrome should be excluded since specific treatment may be required HYPOTHESIS The use of laryngeal mask airway and propofol in inguinal hernia repair results in shorter operative and recovery room times . DESIGN R and omized control trial . SETTING University hospital . PATIENTS From May 2000 to March 2002 , a convenience sample of 79 patients was invited to participate ; 34 entered the study . Fifteen patients were r and omized to subarachnoid block , and 18 patients were r and omized to laryngeal mask airway . No patients withdrew from the study because of adverse effects . All study subjects were followed up for 6 months . INTERVENTION General anesthesia via laryngeal mask airway or lidocaine subarachnoid block anesthesia for inguinal hernia repair . MAIN OUTCOME MEASURES Operative and recovery room times ; surgeon evaluation of the adequacy of the anesthetic technique ; 36-Item Short-Form Health Survey scores before and after operation . RESULTS Total time from entry into the operating room to discharge home was slightly longer in the subarachnoid block group ( 285 vs 262 minutes ; 95 % confidence interval , 251 - 317 minutes ) but this difference was not statistically or clinical ly significant . Patient satisfaction was high with both techniques ; patient-reported outcomes were the same . Surgeons rated muscle relaxation and exposure better with the subarachnoid block . CONCLUSIONS We found no differences between short-acting spinal anesthesia and general anesthesia via laryngeal mask airway with intravenous propofol in efficiency or in early or late outcomes after elective inguinal hernia repair . Surgeon and patient preferences appear to be the most important reasons for selecting an anesthetic technique for individual patients undergoing inguinal hernia repair Background Previous studies suggest that intraoperative anesthetic care may influence postoperative pain and recovery from surgery . The authors tested the hypothesis that the addition of intrathecal analgesia to general anesthesia would improve long-term functional status and decrease pain in patients undergoing radical retropubic prostatectomy . Methods One hundred patients received either general anesthesia supplemented with intravenous fentanyl or general anesthesia preceded by intrathecal administration of bupivacaine ( 15 mg ) , clonidine ( 75 & mgr;g ) , and morphine ( 0.2 mg ) . Patients and providers were masked to treatment assignment . All patients received multimodal pain management postoperatively . Primary outcomes included pain and functional status over the first 12 postoperative weeks . Results Patients receiving intrathecal analgesia required more intravenous fluids and vasopressors intraoperatively . Pain was well controlled throughout the study ( mean numerical pain scores < 3 in both groups at all times studied ) . Intrathecal analgesia decreased pain and supplemental intravenous morphine use over the first postoperative day but increased the frequency of pruritus . Pain and functional status after discharge from the hospital did not differ between groups . Intrathecal analgesia significantly decreased the duration of hospital stay ( from 2.8 ± 2.0 to 2.1 ± 0.5 days ; P < 0.01 ) as a result of five patients in the control group who stayed in the hospital more than 3 days . Conclusions The benefits of improved immediate analgesia and decreased morphine requirements result ing from intrathecal analgesia must be weighed against factors such as pruritus , increased intraoperative requirement for fluids and vasopressors , and re sources needed to implement this modality . Further studies are needed to determine the significance of the decrease in duration of hospital stay To compare the outcomes of thoracic epidural block with thoracic paravertebral block for thoracotomy in pediatric patients . A prospect i ve double-blind study . 60 pediatric patients aged 1 - 24 months , ASA II , III scheduled for thoracotomy were r and omly allocated into two groups . After induction of general anesthesia , thoracic epidural catheter was inserted in group E ( epidural ) patients and thoracic paravertebral catheter was inserted in group P ( paravertebral ) patients . Post operative pain score was recorded hourly for 24 hours . Plasma cortisol level was recorded at three time points . Tidal breathing analysis was done preoperatively and 6 hours postoperatively . Analgesia , serum cortisol level , and pulmonary function parameters were comparable in the two groups . However , failure rate ( incorrect placement of catheter ) was significantly higher in epidural group than in paravertebral group ( 7 % versus 0 % , respectively ) . The complications were also significantly higher in epidural group ( vomiting 14.8 % , urine retention 11.1 % and hypotension 14.8 % ) than paravertebral group ( 0 % , 0 % , and 3.6 % , respectively ) . We conclude that both thoracic paravertebral block and thoracic epidural block results in comparable pain score and pulmonary function after thoracotomy in pediatric patients ; the paravertebral block is associated with significantly less failure rate and side effects Background : There is a need for new clinical models to investigate effectively the development of pain after surgery and the effect , if any , of pre‐emptive treatment . Bilateral models are of special interest , since the patient serves as his/her own control . The objective of this preliminary study was to test a clinical model for the study of acute and chronic pain after bilateral reduction mammoplasty BACKGROUND Concern has been expressed that epidural analgesia for labour may be associated with a higher incidence of backache . METHODS A prospect i ve r and omized trial investigating the effect of epidural analgesia on the outcome of labour in nulliparae , mothers were r and omized to receive either epidural analgesia or meperidine . A question naire on postnatal symptoms was sent to them 6 months after delivery . RESULTS In all , 611 mothers were studied ; 310 were r and omly allocated to receive i.m . meperidine up to 300 mg and 301 to receive epidural bupivacaine . The response rate to our question naire was 83 % . Intention-to-treat analysis showed similar prevalence rates of postpartum backache in the epidural ( 48 % ) and meperidine groups ( 50 % ) , with an observed difference ( epidural-meperidine ) of -2 % ( 95 % CI , -11 to + 6 % ) . After excluding mothers with backache before delivery , there were also similar incidence rates of postpartum backache in the epidural ( 29 % ) and meperidine groups ( 28 % ) , observed difference 1 % ( 95 % CI , -8 to + 10 % ) . CONCLUSIONS Epidural analgesia in labour was not associated with an increase in the prevalence or incidence of backache Paravertebral block ( PVB ) seems to decrease postoperative pain and postoperative nausea and vomiting ( PONV ) after breast surgery , but the studies have not been placebo controlled . We studied 60 patients scheduled for breast cancer surgery r and omly given single-injection PVB at T3 with bupivacaine 5 mg/mL ( 1.5 mg/kg ) or saline before general anesthesia . The patient and attending investigators were blinded ; the PVB or the sham block was performed behind a curtain by an anesthesiologist not involved in the study . The patients given PVB with bupivacaine needed 40 % less IV opioid medication ( primary outcome variable ) in the postanesthesia care unit , had a longer latency to the first opioid dose , and had less pain at rest after 24 h than the control patients ( P < 0.01 ) . They also had less PONV in the postanesthesia care unit ( P < 0.05 ) , were less se date d until 90 min ( P < 0.05 ) , and performed better in the digit symbol substitution test at 90 min and the ocular coordination test 60–120 min after surgery ( P < 0.05 ) . The average peak bupivacaine plasma concentration was 750 ng/mL. One patient had bilateral convulsions immediately after bupivacaine injection . We conclude that PVB before general anesthesia for breast cancer surgery reduced postoperative pain , opioid consumption , and occurrence of PONV and improved recovery from anesthesia BACKGROUND Chronic pain is a common complication after inguinal hernia repair . The objective of this r and omized trial was to assess the effect of intraoperative infiltration with local anesthetic versus placebo on the development of chronic pain after inguinal hernia repair . METHODS Patients with single- or double-sided inguinal hernia were enrolled in a r and omized , controlled , triple-blinded trial with a sequential adaptive design . Hernias were r and omized to 1 of 2 treatment groups . The intervention group received a local infiltration of 20 mL bupivacaine 0.25 % and the placebo group 20 mL saline 0.9 % at the end of the operation . Two interim analyses were performed according to predefined stopping criteria allowing for design and sample size adaption . The primary endpoint was chronic pain defined on a visual analog scale ( VAS ) as ≥30 in any quality ( at rest , lying , walking , climbing stairs , and bending over ) 3 months postoperatively . A logistic regression model was built to compare the incidence of chronic pain using generalized estimating equations to adjust for clustering in bilateral hernias . RESULTS Among 357 patients , there were 406 hernias r and omized . A total of 5.8 % ( 10/173 ) experienced VAS ≥ 30 in any quality in the intervention group and 2.3 % ( 4/174 ) in the placebo group ( P = .114 ) at 3 months postoperatively . Multivariable analysis revealed no evidence of between-group differences for the development of any pain ( odds ratio [ OR ] , 1.03 ; 95 % CI , 0.67 - 1.57 ; P = .905 ) , whereas preoperative pain was an independent risk factor ( OR , 2.52 ; 95 % CI , 1.12 - 5.68 ; P = .025 ) . CONCLUSION We did not find any evidence that intraoperative infiltration of local anesthetic had an impact on the development of chronic postoperative pain Objectives To investigate possible short and long term side effects of epidural analgesia , compared with non‐epidural analgesia for pain relief in labour Study Design . A r and omized , double-blind placebo controlled trial in multimodal analgesia for postoperative pain was conducted . Objective . To examine whether combination of corticosteroid and bupivacaine administered in patients undergoing posterior lumbosacral spine surgery reduces postoperative morphine consumption , back and leg pain relief , and improves functional disability and general health status . Summary of Background Data . Patients with lumbar spine surgery had moderate to severe postoperative pain . Administration of corticosteroid or injection of local anesthetic agent has been additive treatment methods for opioid drugs . There is uncertainty as to whether corticosteroid and bupivacaine combination improves outcomes in lumbosacral spine surgery . Methods . A total of 103 patients who were scheduled to undergo elective posterior lumbar discectomy , decompressive laminectomy with or without instrumented fusion for degenerative spinal diseases , received either methylprednisolone locally applied to the affected nerve roots ( and bupivacaine was infiltrated into the wound ) or injected placebo . Morphine consumption and pain scores were recorded at 1 , 2 , 3 , 6 , 12 , 24 , and 48 hours after surgery . Oswestry Index and Short Form SF-36 scores were recorded before surgery and at 1 and 3 months later . Results . Demographic data between the 2 groups were comparable . The cumulative morphine dose and postoperative pain was significantly lower in the study group than in the placebo group ( P = 0.01 and P = 0.001 , respectively ) . When performing subgroup analyses , the beneficial effects were found in all groups of surgery but could not demonstrated statistically significant difference for all subgroup comparisons . There was no significant difference between the 2 groups with regard to pain on cough , Oswestry Index , and SF-36 scores . No complications were associated with the perioperative use of methylprednisolone or bupivacaine . Conclusions . Administration of methylprednisolone-bupivacaine provided a favorable effect immediately after posterior lumbosacral spine surgery for discectomy , decompression , and /or spinal fusion without complication Transplants from the anterior iliac crest are used for most reconstructive procedures in cranio-maxillofacial surgery . The advantages are easy accessibility , the ability to work in two teams and the amount of corticocancellous bone available ; disadvantages are postoperative pain and gait disturbances . To reduce donor-site pain , the effect of a single dose of bupivacaine ( 10 cc of 2.5mg/cc with 1:80.000 epinephrine ) was studied . 200 consecutive patients , who underwent anterior iliac crest bone harvesting for reconstructive procedures , were r and omly divided into those receiving bupivacaine and those not . They completed a st and ardized question naire . Patients scored the intensity of the pain and difficulties walking at different times with a visual analogue scale . They recorded analgesics used . 98 question naires were eligible for analysis . No differences between the bupivacaine and the control group were detected for postoperative pain and gait disturbance . There is no support for administration of a single dose of bupivacaine to reduce pain in the first postoperative days . The surface area of the removed bone had a significant influence on pain and walking ; pain is related to the local osseous damage or periosteal stripping rather than to the length of incision or the operation time & NA ; We investigated whether intraoperative ‘ subanesthetic doses ’ of ketamine have a postoperative anti‐hyperalgesic and an analgesic effect and which is the preferential route of administration , either systemic ( intravenous , i.v . ) or epidural . One hundred patients scheduled for rectal adenocarcinoma surgery under combined epidural/general anesthesia were included . Before skin incision all the patients received an epidural bolus followed by an infusion of continuous bupivacaine/sufentanil/clonidine mixture . They were r and omly assigned to receive no ketamine ( group 1 ) , i.v . ketamine at the bolus dose of 0.25 mg/kg followed by an infusion of 0.125 mg/kg per h ( group 2 ) , 0.5 mg/kg and 0.25 mg/kg per h ( group 3 ) , epidural ketamine 0.25 mg/kg and 0.125 mg/kg per h ( group 4 ) , or 0.5 mg/kg and 0.25 mg/kg per h ( group 5 ) . All i.v . and epidural analgesics were stopped at the end of surgery and patients were connected to an i.v . morphine patient‐controlled analgesia ( PCA ) device . Short‐term postoperative analgesia ( 72 h ) was assessed by pain visual analog scale scores at rest , cough , and movements as well as by PCA requirements . Wound mechanical hyperalgesia was evaluated and residual pain was assessed by asking the patients at 2 weeks , and 1 , 6 , and 12 months . The area of hyperalgesia and morphine PCA requirements were significantly reduced in group 3 . These patients reported significantly less residual pain until the sixth postoperative month . These observations support the theory that subanesthetic doses of i.v . ketamine ( 0.5 mg/kg bolus followed by 0.25 mg/kg per h ) given during anesthesia reduce wound hyperalgesia and are a useful adjuvant in perioperative balanced analgesia . Moreover , they show that the systemic route clearly is the preferential route Study Design . Parallel design , prospect i ve , double-blinded , r and omized , controlled trial composed of 2 independent groups treated with a continuous infusion catheter ( saline vs. Marcain ) placed into the iliac crest bone graft site ( ICBG ) . Objective . To determine the long-term effects of postoperative continuous local anesthetic agent infusion at the ICBG harvest site in reducing chronic pain , narcotic usage and improving long-term , postoperative function and satisfaction with the surgical procedure . Summary of Background Data . Harvesting iliac crest bone has been shown to be a source of pain and morbidity . In our initial study , we reported that patients who received local anesthetic at the graft site noted a reduction in acute postoperative pain ( VAS ) and narcotic usage . Methods . Twenty-six patients underwent posterior iliac crest bone graft harvesting . Patients were r and omly assigned to receive 96 mL ( 2 mL/h × 48 hours ) of either 0.5 % Marcain or normal saline delivered via a continuous infusion catheter placed at the ICBG harvest site . Postoperative pain scores , narcotic use/frequency , activity level , and length of stay ( LOS ) were recorded and reported previously . At a minimum of 4 years after surgery ( mean , 4.7 years ; range , 4.5–5.4 years ) , all patients completed a question naire documenting their current VAS pain score ( iliac crest ) , frequency of pain ( days per month ) , level of activity , chronic pain at the ICBG site , and overall satisfaction with the procedure . Results . Nine of 11 patients ( 82 % ) in the treatment group and 10 of 14 patients ( 71 % ) in the control group were available at final follow-up ( 1 death occurred in the control group unrelated to the study ) . The treatment group had a statistically significant decrease in the graft site pain VAS score ( 1.4 vs. 4.8 ) and increased satisfaction with the procedure at a minimum of 4 years postprocedure ( P < 0.05 ) . Additionally , no patient in the treatment group developed chronic iliac crest dysesthesias ( 0 of 9 ) versus 7 of 10 patients ( 70 % ) in the control group ( P < 0.05 ) . Conclusion . Continuous infusion of 0.5 % Marcain at the ICBG harvest site significantly reduced chronic dysesthesias . Overall satisfaction with the procedure , number of painful days per month , and VAS scores were significantly better in the treatment group at 4 years . No long-term complications were attributed to either the ICBG site or the catheter-infusion system . The use of continuous local anesthetic infusion at the iliac crest may help in alleviating graft-related pain beyond the perioperative phase BACKGROUND Epidural analgesia before limb amputation is commonly used to reduce postamputation pain . But there have been no controlled studies with large numbers of patients to prove such a pre-emptive effect . We investigated whether postamputation stump and phantom pain in the first year is reduced by preoperative epidural blockade with bupivacaine and morphine . METHODS In a r and omised , double-blind trial , 60 patients scheduled for lower-limb amputation were r and omly assigned epidural bupivacaine ( 0.25 % 4 - 7 mL/h ) and morphine ( 0.16 - 0.28 mg/h ) for 18 h before and during the operation ( 29 patients ; blockade group ) or epidural saline ( 4 - 7 mL/h ) and oral or intramuscular morphine ( 31 patients ; control group ) . All patients had general anaesthesia for the amputation and were asked about stump and phantom pain after 1 week and then after 3 , 6 , and 12 months by two independent examiners . Study endpoints were rate of stump and phantom pain , intensity of stump and phantom pain , and consumption of opioids . FINDINGS Two patients in each group were withdrawn before amputation . The groups were well matched in baseline characteristics . Median duration of preoperative saline treatment was 18.5 h ( IQR 17 - 20 ) . Median duration of preoperative epidural blockade in the blockade group was 18 h ( 15 - 20.3 ) . The combined median duration of postoperative epidural pain treatment in both groups was 166 h ( 89.3 - 308.3 ) . After 1 week , 14 ( 52 % ) patients in the blockade group and 15 ( 56 % ) in the control group had phantom pain ( 95 % CI - 30.6 to 22.7 , p = 0.9 ) . The figures for blockade versus control group were : 14 ( 82 % ) vs ten ( 50 % ; 4.0 to 60.8 , p = 0.09 ) at 3 months ; 13 ( 81 % ) vs 11 ( 55 % ; -2.7 to 55.3 , p = 0.2 ) at 6 months ; and nine ( 75 % ) vs 11 ( 69 % ; -27.0 to 39.6 , p = 1.0 ) at 12 months . Intensity of stump and phantom pain and consumption of opioids were similar in both groups at all four postoperative interviews . INTERPRETATION Perioperative epidural blockade started a median of 18 h ( 15 - 20.3 ) before the amputation and continued into the postoperative period does not prevent phantom or stump pain We have studied the use of intra-vas deferens local anaesthesia in 70 patients undergoing vasectomy as day-case patients . Patients were allocated r and omly to either a control or treatment group . In the treatment group , 0.5 % bupivacaine 1 ml or 0.9 % saline 1 ml was injected into the lumen of the right or left vas deferens in a r and omized blinded design . The control group did not receive an injection . Patients were discharged with a question naire for recording visual analogue scores ( VAS ) for both the right and left sides to be scored on days 1 and 7 after operation . One year after the procedure a second question naire was sent out asking about the presence or absence of chronic testicular discomfort , its duration and any surgical intervention required to relieve it . There were no differences between the control group and the saline side of the treatment group in VAS scores on both day 1 and day 7 after operation or in the incidence and duration of chronic testicular discomfort ( mean 30 ( SD 53 ) and 34 ( 50 ) days , respectively ) . The VAS scores were , however , significantly less ( P < 0.005 ) and testicular discomfort was absent on the bupivacaine-treated side Background and Objectives : Wound infiltration with available local anesthetics generally provides analgesia for less than 8 hrs . The site 1 sodium-channel toxin neosaxitoxin ( neoSTX ) produced analgesia for over 24 hrs in animals and human volunteers . In this r and omized , double-blind trial , we examined the postoperative course of patients undergoing laparoscopic cholecystectomy under a st and ardized general anesthesia with wound infiltration using either neoSTX or bupivacaine . We hypothesized that neoSTX would reduce pain compared with bupivacaine at 12 hrs postoperatively . Methods : Patients received preincisional infiltration of laparoscope entry sites with 20 mL containing either neoSTX ( total dose , 100 & mgr;g ) or bupivacaine 0.25 % ( total dose , 50 mg ) . The primary outcome measure was the visual analog pain score at 12 hrs postoperatively . Secondary outcomes included repeated pain scores at rest and with movement , analgesic use , functional recovery , and adverse effects . Groups were compared using Mann-Whitney U tests for pain scores , Fisher exact test for proportions of patients with severe pain and complete analgesia , and Kaplan-Meier curves for time to full recovery . Results : Among 137 subjects , 69 were r and omized to neoSTX and 68 to bupivacaine . Median pain scores at rest and with movement 12 hrs postoperatively were lower in the neoSTX group compared with the bupivacaine group ( P < 0.01 ) . Additional pain measures and recovery parameters also favored neoSTX . No serious adverse events occurred , and no adverse events were more frequent in the neoSTX group . Conclusions : NeoSTX shows promise as a long-acting local anesthetic . Future studies will examine dose response , combination formulations , and safety with dose escalation Objectives Prolonged activation of pain centers is a proposed cause of chronic pain syndromes . Women are at particular risk for chronic pain as they tend to more readily detect pain and to attenuate it less than men . We set out to determine whether sex affected pain and recovery after major surgery by analyzing data originally collected to determine the effect of the timing of epidural analgesia on long-term outcome after thoracotomy . Methods Patients presenting for lobectomy , segmentectomy , or bilobectomy , but not pneumonectomy or chest wall resection , were enrolled . Pain , physical activity , and the extent that pain interfered with activities after surgery were prospect ively assessed with st and ard question naires ( Brief Pain Inventory and physical component score of SF-36 ) on postoperative days 1 to 5 , and at postoperative weeks 4 , 8 , 12 , 24 , 36 , and 48 by a blinded research assistant . Perioperative care was st and ardized and included patient-controlled thoracic epidural analgesia until thoracostomy tube removal . Results Fifty eight men and 62 women were enrolled . Women reported more pain than men throughout the entire study period , and they had a higher rate of nonsteroidal anti-inflammatory drug use , but not opioid use . This increased pain was not explained by incision type , surgeon , tumor type , or tumor stage . Older patients reported less pain after discharge than younger patients . Postoperative physical activity levels were significantly less than those reported preoperatively , but did not differ by sex . Discussion Women have a distinctly different pain experience than men after thoracic surgery and probably require novel and /or multimodal analgesic regimens to improve their comfort BACKGROUND The infusion of local anesthetic in the surgical wound is helpful in the multimodal management of postoperative pain . We hypothesized that local anesthetic wound infusion after cesarean delivery would provide better pain control than epidural morphine analgesia . METHODS Healthy , term women scheduled for elective cesarean delivery were included in this assessor-blinded , r and omized study . Patients were r and omly assigned to receive analgesia through a multiorifice wound catheter placed below the fascia and connected to a 5 mL/h ropivacaine 2 mg/mL infusion or an epidural bolus of morphine 2 mg every 12 hours . Both analgesic regimens were continued for 48 hours . The primary outcome was pain at rest at 24 hours postoperatively using the verbal rating score for pain ( 0 - 10 scale ) . Pain intensity , rescue analgesia consumption , and side effects were assessed at 2 , 6 , 24 , and 48 hours after cesarean delivery by an observer blinded to group allocation . Three months after discharge , patient satisfaction , residual pain , and surgical wound complications were assessed . RESULTS Fifty-eight women participated in the study . At 24 hours , the median rest verbal rating score for pain was 0 ( interquartile range : 0 - 0 ) in the continuous infusion group and 3 in the epidural morphine group ( interquartile range : 2 - 3 ; 95 % confidence interval of difference : 1 - 3 units ; P < 0.001 ) . The median scores of the 2- , 6- , and 48-hour pain assessment s at rest were also lower in the continuous wound infusion group than in the epidural morphine group , and at 2 , 6 , and 24 hours with movement ( P < 0.001 ) . The incidence of nausea , vomiting , pruritus , and urinary retention was significantly lower in the wound infusion group and time to recovery of bowel function was shorter . During the 48-hour follow-up evaluation , the median number of nurse visits attributed exclusively to the analgesic regimen was 1 ( interquartile range : 1 - 2 ) in the continuous wound infusion group and 8 ( interquartile range : 7 - 10 ) in the epidural morphine group ( 95 % confidence interval of difference : 6 - 8 visits ; P < 0.001 ) . CONCLUSIONS Continuous wound infusion with ropivacaine for 48 hours after cesarean delivery was associated with better analgesia , a lower incidence of side effects , less need for nursing care , and shorter duration of stay compared with epidural morphine analgesia OBJECTIVE To investigate the relationships between 2 anesthetic techniques , or the extent of allodynia around the surgical wound , and the occurrence of chronic post-thoracotomy pain . DESIGN Prospect i ve , r and omized study . SETTING A single-institution , university hospital . PARTICIPANTS Thirty-eight patients who underwent elective thoracotomy under general anesthesia . INTERVENTIONS High-dose remifentanil ( average effect-site concentration 5.61 + /- 0.84 ng/mL ) with epidural analgesia started and at the end of surgery or low-dose remifentanil ( average effect site concentration 1.99 + /- 0.02 ng/mL ) with epidural analgesia with 0.5 % ropivacaine started at the beginning of anesthesia . MEASUREMENTS AND MAIN RESULTS Pain intensity and the extent of allodynia around the wound were measured during the hospital stay . The presence and intensity of residual pain were assessed 1 , 3 , and 6 months after surgery and at the end of the study ( 6 - 13 months , average 9 months ) . A DN4 neuropathic pain diagnostic question naire was conducted at the same times . In the high-dose group , the area with allodynia was three times larger than the area in the low-dose group . The increased allodynia was associated with a higher incidence of chronic pain ( RR : 2.7 - 4.2 ) 3 and 6 months after surgery and at the end of the study ( median follow-up : 9.5 months ) . CONCLUSIONS High-dose remifentanil ( 0.14 - 0.26 microg/kg/min ) without epidural analgesia during surgery is associated with a large area of allodynia around the wound . These patients develop a much higher incidence of chronic pain than those receiving low-dose remifentanil with epidural analgesia during surgery OBJECTIVE To compare the postoperative analgesic effects of continuous wound infusion of ropivacaine with traditional patient-controlled analgesia ( PCA ) with sufentanil after non-cardiac thoracotomy . METHODS One hundred and twenty adult patients undergoing open thoracotomy were recruited into this assessor-blinded , r and omized study . Patients were r and omly assigned to receive analgesia through a wound catheter placed below the fascia and connected to a 2 ml/h ropivacaine 0.5 % ( RWI group ) or sufentanil PCA ( SPCA group ) . Analgesia continued for 48 h. Visual analogue scores ( VAS ) at rest and movement , Ramsay scores and adverse effects were recorded at 2 , 8 , 12 , 24 , 36 and 48 h after surgery . Three months after discharge , patient 's satisfaction , residual pain and surgical wound complications were assessed . RESULTS General characteristics of patients were comparable between two groups . There were no statistical differences in the VAS scores and postoperative pethidine consumption between two groups ( P > 0.05 ) . However , when compared with SPCA group , the incidences of drowsiness , dizziness and respiratory depression , ICU stay and hospital expenditure reduced significantly in RWI group ( P < 0.05 ) . Patients ' satisfaction with pain management was also improved markedly in RWI group ( P < 0.05 ) . CONCLUSION Continuous wound infusion with ropivacaine is effective for postoperative analgesia and has comparable effects to traditional PCA with sufentanil . Furthermore , this therapy may also reduce the incidences of drowsiness , dizziness , respiratory depression and decrease the ICU stay and hospital expenditure & NA ; Persistent pain has been reported in up to 80 % of patients after limb amputation . The mechanisms are not fully understood , but nerve injury during amputation is important , with evidence for the crucial involvement of the spinal N‐methyl d‐aspartate ( NMDA ) receptor in central changes . The study objective was to assess the effect of pre‐emptively modulating sensory input with epidural ketamine ( an NMDA antagonist ) on post‐amputation pain and sensory processing . The study recruited 53 patients undergoing lower limb amputation who received a combined intrathecal/epidural anaesthetic for surgery followed by a r and omised epidural infusion ( Group K received racemic ketamine and bupivacaine ; Group S received saline and bupivacaine ) . Neither general anaesthesia nor opioids were used during the peri‐operative period . Pain characteristics were assessed for 12 months . The primary endpoint was incidence and severity of post‐amputation pain . Persistent pain at one year was much less in both groups than in comparable studies , with no significant difference between groups ( Group K = 21 % ( 3/14 ) and 50 % ( 7/14 ) ; and Group S = 33 % ( 5/15 ) and 40 % ( 6/15 ) for stump and phantom pain , respectively ) . Post‐operative analgesia was significantly better in Group K , with reduced stump sensitivity . The intrathecal/epidural technique used , with peri‐operative sensory attenuation , may have reduced ongoing sensitisation , reducing the overall incidence of persistent pain . The improved short‐term analgesia and reduced mechanical sensitivity in Group K may reflect acute effects of ketamine on central sensitisation . Longer term effects on mood were detected in Group K that requires further study Background The aim of this study was to evaluate the postoperative morphine-sparing effects and reduction in pain and secondary mechanical hyperalgesia after preincisional or postincisional epidural administration of a local anesthetic and an opioid compared with a sham epidural control . Methods Patients undergoing major gynecologic surgery by laparotomy were r and omly assigned to three groups and studied in a double-blinded manner . Group 1 received epidural lidocaine and fentanyl before incision and epidural saline 40 min after incision . Group 2 received epidural saline before incision and epidural lidocaine and fentanyl 40 min after incision . Group 3 received a sham epidural control ( with saline injected into a catheter taped to the back ) before and 40 min after incision . All patients underwent surgery with general anesthesia . Results One hundred forty-one patients completed the study ( group 1 , n = 45 ; group 2 , n = 49 ; group 3 , n = 47 ) . Cumulative patient-controlled analgesia morphine consumption at 48 h was significantly lower ( P = 0.04 ) in group 1 ( 89.8 ± 43.3 mg ) than group 3 ( 112.5 ± 71.5 mg ) but not group 2 ( 95.4 ± 60.2 mg ) , although the hourly rate of morphine consumption between 24 and 48 h after surgery was significantly lower ( P < 0.0009 ) in group 1 ( 1.25 ± 0.02 mg/h ) than group 2 ( 1.41 ± 0.02 mg/h ) . Twenty-four hours after surgery , the visual analog scale pain score on movement was significantly less intense ( P = 0.005 ) in group 1 ( 4.9 ± 2.2 cm ) than group 3 ( 6.0 ± 2.6 cm ) but not group 2 ( 5.3 ± 2.5 cm ) , and the von Frey pain threshold near the wound was significantly higher ( P = 0.03 ) in group 1 ( 6.4 ± 0.6 log mg ) than in group 3 ( 6.1 ± 0.8 log mg ) but not group 2 ( 6.2 ± 0.7 log mg ) . Conclusions Preincisional administration of epidural lidocaine and fentanyl was associated with a significantly lower rate of morphine use , lower cumulative morphine consumption , and reduced hyperalgesia compared with a sham epidural condition . These results highlight the importance of including a st and ard treatment control group to avoid the problems of interpretation that arise when two-group studies of preemptive analgesia ( preincisional vs. postsurgery ) fail to find the anticipated effects Background : The aim of the study was to compare the efficacy of either ropivacaine or placebo through an iliac crest ( IC ) catheter after Bankart repair with IC bone grafting . Methods : With approval of the local ethics committee and after written informed consent was obtained , 36 patients had an interscalene catheter placed preoperatively . Intraoperatively , the surgeon placed a catheter at the IC donor site . At the end of surgery , 30 ml ropivacaine , 0.5 % ( ropivacaine group ) , or 30 ml NaCl , 0.9 % ( placebo group ) , was administered . Ropivacaine , 0.2 % , was started 6 h after the initial block through the interscalene catheter for 48 h ( t48 ) in all patients . At t0 , the patient received either 5 ml/h ropivacaine , 0.2 % ( ropivacaine group ) , or 5 ml/h NaCl , 0.9 % ( placebo group ) , for 48 h through the IC catheter . All patients received an intravenous morphine patient-controlled analgesia device . Pain scores at the shoulder and at the IC donor site were assessed at rest and during motion every 8 h for 48 h and after 3 months . Plasma concentrations of total and unbound ropivacaine , morphine consumption , and patient satisfaction were assessed . Results : At the IC donor site , pain was significantly lower in the ropivacaine group compared with the placebo group at rest and during motion at any time . Total and unbound plasma concentrations of ropivacaine were below the toxic threshold in both groups . Morphine consumption was significantly lower in the ropivacaine group after 24 and 48 h. Patient satisfaction was significantly higher in the ropivacaine group . At 3 months , pain at the IC during motion was significantly lower in the ropivacaine group . Conclusions : Continuous application of 0.2 % ropivacaine through an IC catheter after Bankart repair with IC bone grafting is an effective method for pain relief for the first 48 h , with few adverse effects and high patient satisfaction . The benefit of this technique is still present after 3 months Introduction Perioperative pain management influences both the quality as well as the speed of recovery following surgery . Methods This was a r and omized double-blind placebo-controlled study design ed to assess the effectiveness of a multimodal analgesic approach ( MMA ) vs patient-controlled analgesia ( PCA ) alone in patients undergoing open prostatectomy . Prior to surgery , paravertebral blocks ( PVBs ) were performed with either 0.5 % ropivacaine in the MMA group or saline in the PCA group . Patients in the MMA group also received celecoxib ( 400 mg po prior to surgery and 200 mg po bid for seven days following surgery ) and ketamine 10 mg iv . Following surgery , every patient had free access to morphine PCA . A pain numerical rating scale ( NRS ) at 24 hr was chosen as the primary endpoint . Secondary endpoints included morphine consumption at 24 hr and SF-36 ( 36-Item Short-Form Health Survey ) scores from two weeks to 24 weeks following surgery . Results The primary endpoint , average pain NRS at 24 hr , was 2.6 in the MMA group compared with 3.9 in the PCA group ( difference = −1.6 , 95 % confidence interval [ CI ] : −2.3 to −0.4 ; P = 0.01 ) . The average morphine consumption at 24 hr was 4.8 mg in the MMA group compared with 10.5 mg in the PCA group ( difference = −5.7 , 95 % CI : −13.0 to 0.5 ; P = 0.01 ) . Higher SF-36 scores at two , four , eight , and 12 weeks were observed in the MMA group compared with the PCA group , but no statistically significant ( P < 0.05 ) between-group difference was found after Bonferroni correction of comparisons conducted repeatedly over time . Postoperative adverse effects included low episodes of postoperative nausea and vomiting , bladder spasms , constipation , and pruritus . Conclusion This study demonstrates that PVBs combined with celecoxib and ketamine provide better immediate postoperative pain control and facilitate earlier functional recovery in patients undergoing an open radical prostatectomy when compared with PCA alone . Résumé Introduction La prise en charge de la douleur périopératoire influence la qualité aussi bien que la rapidité de rétablissement après une chirurgie . MéthodeNous avons réalisé une étude r and omisée contrôlée par placebo à double insu afin d’évaluer l’efficacité d’une approche analgésique multimodale ( AMM ) par rapport à une analgésie contrôlée par le patient ( ACP ) seule chez des patients devant subir une prostatectomie ouverte . Avant la chirurgie , des blocs paravertébraux ( BPV ) ont été réalisés à l’aide de 0,5 % ropivacaïne dans le groupe AMM ou d’un sérum physiologique dans le groupe ACP . Les patients du groupe AMM ont également reçu du célécoxib ( 400 mg po avant la chirurgie et 200 mg po bid pendant 7 jours après la chirurgie ) et de la kétamine 10 mg iv . Après la chirurgie , une ACP de morphine était à disposition de chaque patient . Le critère d’évaluation principal retenu était une échelle d’évaluation numérique ( ÉÉN ) à 24 h. Les critères secondaires étaient la consommation de morphine à 24 h et les scores au question naire SF-36 ( 36-Item Short-Form Health Survey – bref question naire de santé en 36 éléments ) administré entre deux et 24 semaines après la chirurgie . RésultatsLe critère d’évaluation principal , soit la douleur moyenne sur une ÉÉN à 24 h , était de 2,6 dans le groupe AMM par rapport à 3,9 dans le groupe ACP ( différence = −1,6 , intervalle de confiance [ IC ] 95 % : −2,3 à −0,4 ; P = 0,01 ) . La consommation moyenne de morphine à 24 h était de 4,8 mg dans le groupe AMM comparativement à 10,5 mg dans le groupe ACP ( différence = −5,7 , IC 95 % : −13,0 à 0,5 ; P = 0,01 ) . Des scores plus élevés au SF-36 à deux , quatre , huit et 12 semaines ont pu être observés dans le groupe AMM par rapport au groupe ACP , mais aucune différence intergroupe significative d’un point de vue statistique ( P < 0,05 ) n’a été observée après les corrections des comparaisons selon la méthode Bonferroni réalisées à divers intervalles . Les effets secondaires postopératoires étaient de faibles épisodes de nausées et vomissements postopératoires , des spasmes de la vessie , de la constipation et du prurit . Conclusion Cette étude démontre que les BPV combinés au célécoxib et à la kétamine procurent un meilleur soulagement de la douleur postopératoire immédiate et facilitent une récupération fonctionnelle précoce chez les patients subissant une prostatectomie radicale ouverte comparativement à une ACP seule Wound infusion with local anesthetics has been used for postoperative pain relief with variable results . This r and omized , controlled , double-blind clinical trial examines the effect of ropivacaine infusion on pain after laparoscopic cholecystectomy . A total of 110 patients were r and omly assigned to 2 groups . After induction of anesthesia a 75-mm catheter was inserted subcutaneously and connected to an elastomeric pump containing either 0.75 % ropivacaine ( ropivacaine group ) or normal saline ( control group ) for 24 hours postoperatively . Before skin closure , each hole was infiltrated with 2 mL of 0.75 % ropivacaine or normal saline according to r and omization . Pain at rest , pain during cough , and analgesic consumption were recorded in the postanesthesia care unit and at 2 , 4 , 8 , 24 , and 48 hours postoperatively . Analgesic requirements and pain scores were recorded 1 and 3 months after surgery . The ropivacaine group reported less pain during cough ( P=0.044 ) in the postanesthesia care unit ( P=0.017 ) and 4 hours postoperatively ( P=0.038 ) . Ropivacaine wound infusion had no effect on late and chronic pain We evaluated the effect of multimodal analgesia on acute and chronic pain after breast surgery for cancer . Fifty patients scheduled for breast cancer surgery were blindly r and omized to receive gabapentin , eutectic mixture of local anesthetics cream , and ropivacaine in the wound or three placebos . Pain ( visual analog scale ) and analgesics were recorded in the postanesthesia care unit ( PACU ) 3 , 6 , and 9 h and 8 days after surgery . Three and 6 mo later , patients were assessed for chronic pain . The treatment group consumed less paracetamol in the PACU ( 469 versus 991 mg ; P < 0.002 ) and less Lonalgal ® ( 1.0 versus 4.4 tablets ; P = 0.003 ) than the controls , exhibited lower visual analog scale scores at rest in the PACU ( P = 0.001 ) and on postoperative Days 1 , 3 , and 5 ( P = 0.040 , P = 0.015 , and P = 0.045 , respectively ) , and after movement in the PACU ( P = 0.001 ) and on postoperative Days 2 , 4 , and 8 ( P = 0.028 , P = 0.007 , and P = 0.032 , respectively ) . Three and 6 mo after surgery , 18 of 22 ( 82 % ) and 12 of 21 ( 57 % ) of the controls reported chronic pain versus 10 of 22 ( 45 % ) and 6 of 20 ( 30 % ) in the treatment group ( P = 0.028 and P = 0.424 , respectively ) ; 5 of 22 and 4 of 21 of the controls required analgesics versus 0 of 22 and 0 of 20 of those treated ( P = 0.048 and P = 0.107 , respectively ) . Multimodal analgesia reduced acute and chronic pain after breast surgery for cancer Background and Objectives A significant percentage of women undergoing breast surgery for cancer may develop neuropathic pain in the chest , and /or ipsilateral axilla and /or upper medial arm , with impairment in performing daily occupational activities . We design ed this study to determine if the perioperative application of EMLA ( eutectic mixture of local anesthetics ; AstraZeneca ) cream in the breast and axilla area reduces analgesic requirements , as well as the acute and chronic pain after breast surgery . Methods Forty-six female patients scheduled for breast surgery received r and omly 5 g of EMLA or placebo on the sternal area 5 minutes before surgery , and 15 g on the supraclavicular area and axilla at the end of the operation . Treatment with EMLA cream ( 20 g ) or placebo was also applied daily on the 4 days after surgery . In the postanesthesia care unit ( PACU ) , 3 , 6 , 9 , and 24 hours after surgery , and on the second to sixth day postoperatively , pain was assessed by visual analogue scale ( VAS ) at rest and after movement , and postoperative analgesic requirements were recorded . Three months later , patients were asked if they had pain in the chest wall , axilla and /or medial upper arm , decreased sensation , if they required analgesics at home , and for the intensity of pain . Results Acute pain at rest and with movement did not differ between the EMLA and control groups , and the analgesics consumed during the first 24 hours were the same for the EMLA and control groups . However , time to the first analgesia requirement was longer ( P = .04 ) , and codeine and paracetamol consumption during the second to fifth days was less ( P = .001 , and P = .004 , respectively ) in the EMLA versus the control group . Three months postoperatively , pain in the chest wall , axilla , and the total incidence and the intensity of chronic pain were significantly less in the EMLA versus the control group ( P = .004 , P = .025 , P = .002 and P = .003 , respectively ) . The use of analgesics at home and abnormal sensations did not differ between the 2 groups . Conclusions The application of EMLA to patients undergoing breast surgery for cancer reduced the postoperative analgesic requirements and the incidence and intensity of chronic pain Background : Chronic postsurgical pain ( CPSP ) has been linked to many surgical setting s. The authors aim ed to analyze functional genetic polymorphisms and clinical factors that might identify CPSP risk after inguinal hernia repair , hysterectomy , and thoracotomy . Methods : This prospect i ve multicenter cohort study enrolled 2,929 patients scheduled for inguinal hernia repair , hysterectomy ( vaginal or abdominal ) , or thoracotomy . The main outcome was the incidence of CPSP confirmed by physical examination 4 months after surgery . The secondary outcome was CPSP incidences at 12 and 24 months . The authors also tested the associations between CPSP and 90 genetic markers plus a series of clinical factors and built a CPSP risk model . Results : Within a median of 4.4 months , CPSP had developed in 527 patients ( 18.0 % ) , in 13.6 % after hernia repair , 11.8 % after vaginal hysterectomy , 25.1 % after abdominal hysterectomy , and 37.6 % after thoracotomy . CPSP persisted after a median of 14.6 months and 26.3 months in 6.2 % and 4.1 % , respectively , after hernia repair , 4.1 % and 2.2 % after vaginal hysterectomy , 9.9 % and 6.7 % after abdominal hysterectomy , and 19.1 % and 13.2 % after thoracotomy . No significant genetic differences between cases and controls were identified . The risk model included six clinical predictors : ( 1 ) surgical procedure , ( 2 ) age , ( 3 ) physical health ( Short Form Health Survey-12 ) , ( 4 ) mental health ( Short Form Health Survey-12 ) , ( 5 ) preoperative pain in the surgical field , and ( 6 ) preoperative pain in another area . Discrimination was moderate ( c-statistic , 0.731 ; 95 % CI , 0.705 to 0.755 ) . Conclusions : Until unequivocal genetic predictors of CPSP are understood , the authors encourage systematic use of clinical factors for predicting and managing CPSP risk Background In a previous r and omized , triple-masked , placebo-controlled study , the authors demonstrated that extending a single-injection paravertebral nerve block with a multiple-day perineural local anesthetic infusion improves analgesia and decreases pain-related dysfunction during the 3-day infusion but not subsequent to catheter removal within 1 month after mastectomy . This report describes a prospect i ve follow-up study of the previously published trial to investigate the possibility that extending a single-injection paravertebral block with a multiple-day infusion may decrease persistent postsurgical pain as well as pain-induced emotional and functional dysfunction 1 year after mastectomy . Methods Subjects undergoing uni- or bilateral mastectomy received unilateral ( n = 24 ) or bilateral ( n = 36 ) single-injection thoracic paravertebral block(s ) with ropivacaine and perineural catheter(s ) . The subjects were r and omized to receive either ropivacaine 0.4 % ( n = 30 ) or normal saline ( n = 30 ) via their catheters until the catheters were removed on postoperative day 3 . Chronic pain and pain-related physical and emotional dysfunction were measured using the Brief Pain Inventory ( BPI ) . Results No statistically significant difference between treatments 3 months after surgery was observed with the BPI . In contrast , after 12 months , only 4 subjects ( 13 % ) who had received a perineural ropivacaine infusion reported pain-induced dysfunction compared with 14 ( 47 % ) who had received saline infusion ( P = 0.011 ) . At 12 months , the mean BPI was 1.6 ± 4.6 for the subjects who received ropivacaine versus 5.9 ± 11.3 for the subjects who received saline ( P = 0.007 ) . Conclusions Adding a multiple-day , continuous ropivacaine infusion to a single-injection ropivacaine paravertebral nerve block may result in a lower incidence of pain as well as pain-related physical and emotional dysfunction 1 year after mastectomy OBJECTIVE Minimally invasive pectus excavatum repair is a common and painful surgical procedure in children and adolescents . Adequate postoperative pain therapy is important far beyond the immediate postoperative period because sensitization to painful stimuli can cause chronic pain or higher pain levels during subsequent surgical procedures . Although data in adults favor thoracic epidural anesthesia for pain control in thoracotomy , data for adolescents and children are scarce . We tested the hypothesis that pain relief with thoracic epidural analgesia was superior to that with intravenous patient-controlled analgesia after minimally invasive pectus excavatum repair in children and adolescents . METHODS We performed a prospect i ve r and omized trial with adolescents who had undergone minimally invasive pectus excavatum repair to compare postoperative pain using two different postoperative pain therapy setting s : intravenous patient-controlled analgesia ( n = 20 ) with morphine versus continuous thoracic epidural analgesia ( n = 20 ) with 0.2 % ropivacain containing 2 microg/mL fentanyl . RESULTS Forty patients ( 32 male and 8 female patients ) aged 10 to 28 years were studied . The thoracic epidural analgesia group showed lower pain scores ( P < .0001 ) and required less additional pain medication in conjunction with greater well-being postoperatively ( P < .0001 ) compared with patients receiving patient-controlled intravenous morphine . There was no significant difference regarding the incidence of sedation ( P = .38 ) , nausea ( P = .10 ) , and pruritus ( P = .72 ) in both groups . CONCLUSIONS For adolescents undergoing minimally invasive pectus excavatum repair , thoracic epidural analgesia was superior to intravenous patient-controlled analgesia for postoperative analgesia , result ing in lower postoperative pain scores in conjunction with greater well-being BACKGROUND Thoracic surgeons spend a lot of time treating the pain of thoracotomy . METHODS A total of 119 consecutive patients underwent elective thoracotomy . They were prospect ively r and omized into two groups . One group received an injection of 1 % lidocaine with epinephrine in the planned skin incision just before thoracotomy , and the other group received an equal amount of saline and epinephrine . All patients had a functioning preoperative epidural ; a skin incision the width of their latissimus dorsi muscle , which was cut ; sparing of the serratus anterior muscle ; undercutting of the sixth rib ; intercostal nerve blocks before rib spreading ; a similar number of chest tubes and pulmonary resections ; and comparable postoperative pain management . Pain was objectified by a numeric pain score , a visual pain score , and by the Modified McGill pain question naire each day in the hospital , and at 3 , 6 , and 12 months postoperatively . RESULTS There were 66 patients in the lidocaine group ( L group ) and 53 patients in the saline group ( S group ) . Although a trend was noted toward less pain in the L group during the first 3 postoperative days ( on the numeric pain scale only ) the difference was not statistically significant in overall pain in the hospital or at 3 , 6 , and 12 months after the operation . Other pain scores and descriptors were similar throughout . CONCLUSIONS The injection of lidocaine and epinephrine in the skin just before thoracotomy does not decrease the amount or type of pain during the hospital stay or at 3 , 6 , and 12 months after surgery OBJECTIVES Thoracic surgery is associated with severe acute postoperative pain , leading to pulmonary complications and hyperalgesia-induced chronic pain . Thoracic patient-controlled epidural analgesia is also considered as the gold-st and ard postoperative analgesia . As previously described in major digestive surgery , combination with low-dose intravenous ( i.v . ) ketamine could potentiate epidural analgesia and facilitate pulmonary function recovery following thoracotomy . METHODS In a r and omized , double-blind trial , 60 patients scheduled to undergo thoracotomy were included . All patients received a thoracic epidural catheter placed before surgery , and st and ardized general anaesthesia . They were allocated to two groups to receive either an i.v . bolus of ketamine at induction , followed by a continuous infusion during surgery and the first 48 h postoperatively , or an i.v . placebo ( a saline solution under the same infusion modalities ) . Cumulative epidural ropivacaine consumption , postoperative pain scores ( patient self-rated numeric pain intensity scale ) , analgesic rescue consumption , residual pain , haemodynamics and respiratory recovery function were recorded from 12 h to 3 months . Data were expressed as mean ± st and ard deviation or median ± interquartile range ( 25 - 75 % ) . The comparisons between ketamine and placebo groups were performed using χ(2 ) or Fisher 's exact tests for frequencies , and Mann-Whitney tests for quantitative variables . RESULTS Epidural ropivacaine consumption was similar between groups during the first 48 postoperative hours . Postoperative pain scores and spirometric parameters were not significantly different between groups . But the incidence of postoperative nausea was significantly increased in patients owning to the ketamine group . Finally , the incidence of residual pain was similar between groups at 1 and 3 months following thoracotomy . CONCLUSIONS Adding i.v . ketamine did not potentiate epidural analgesia neither to reduce acute and chronic postoperative pain nor to improve pulmonary dysfunction following thoracic surgery . Pain scores were low in both groups , mainly because of an optimized analgesia provided by the patient-controlled epidural mode , and might explain this lack of benefit in adding i.v . ketamine BACKGROUND The analgesic benefit of TAP ( transversus abdominis plane ) blocks for cesarean delivery pain remains controversial . We compared the analgesic efficacy of two doses of local anesthetic for TAP blocks after cesarean delivery . METHODS Sixty women having cesarean delivery under spinal anesthesia were r and omized to receive ultrasound-guided TAP blocks using either high-dose ropivacaine ( 3mg/kg ) , low-dose ropivacaine ( 1.5mg/kg ) or placebo . Patients received intrathecal 0.75 % bupivacaine 10 - 12 mg , fentanyl 10μg and morphine 150μg and st and ard multimodal analgesia . The primary outcome was the difference in pain with movement using a numeric rating scale at 24h . Other outcomes included time to first request for analgesia , pain scores at 6 , 12 , 36 , 48h and at 6 and 12weeks , opioid consumption , adverse effects , quality of recovery , and satisfaction . RESULTS There were no differences between groups in the primary outcome . Mean ± SD pain scores ( 0 - 10 ) with movement at 24h were : high-dose ropivacaine 3.6±1.5 , low-dose ropivacaine 4.6±2.1 and placebo 4.1±1.7 . With respect to secondary outcomes , the mean ± SD pain scores at 6h were lower in the high-dose group 2.0±1.8 compared to the low-dose 3.4±2.7 and placebo groups 4.2±2.0 ( P=0.009 ) . Pain scores at 12h were also lower in the high-dose group 2.2±2.0 compared to the low-dose group 4.1±2.7 and placebo group 4.0±1.3 ( P=0.011 ) . There was no difference in other outcomes between groups . CONCLUSIONS Neither high- or low-dose TAP blocks as part of a multimodal analgesia regimen including intrathecal morphine improved pain scores with movement at 24h after cesarean delivery when compared to placebo TAP blocks . High-dose TAP blocks may improve pain scores up to 12h after cesarean delivery INTRODUCTION Reduced postoperative pain is one of the many factors that have driven the growing emphasis on the role of laparoscopic surgery for surgical management . Several studies have documented the advantages of the laparoscopic repair of ventral hernias compared to the open ventral herniorraphy . However , the laparoscopic approach may be associated with more postoperative pain initially . In this preliminary study , we present data from our early experience with the use of a lidocaine patch for pain control in the immediate postoperative period following laparoscopic ventral hernia repair ( LVH ) . METHODS Thirty consecutive patients underwent laparoscopic ventral herniorraphy ( LVH ) and were selected r and omly and placed into one of two groups . In one group , we placed a lidocaine patch ( LP ) ( Lidoderm , Endo Pharmaceuticals , Inc. , Chadds Ford , PA ) on the anterior abdominal wall corresponding to the placement site of the underlying mesh in fifteen patients ( Group A ) . In the second group , we did not place a LP on the abdominal wall of fifteen consecutive patients ( Group B ) . We assessed all patients according to their demographic data , Body Mass Index ( BMI ) , American Society of Anesthesiologists ( ASA ) score , the size of the abdominal wall defect ( AWD ) , area of mesh ( size ) used , operative time , length of hospital stay ( LOA ) , morbidity , and the individual patient 's pain score at discharge , two weeks and two months postoperatively . RESULTS The two groups were similar with respect to demographics , BMI , ASA , AWD , size of mesh , LOS and morbidity . Group A had a statistically significant reduction in their postoperative pain score at discharge when compared to Group B ( 3.13+/-1.68 and 4.8+/-1.42 , respectively , p value=0.0067 ) . CONCLUSION In this preliminary study , the use of a lidocaine patch in the management of postoperative pain following laparoscopic ventral herniorraphy is a safe and promising modality to consider in the management of postoperative pain control Objective To evaluate the effects of intraperitoneal instillation of lidocaine on postcesarean pain in patients with pariental periotoneal closure . Methods A sample of 370 pregnant women , presenting early in labor , with no history of abdominal surgery and with indications for cesarean section were operated on with closure of the parietal peritoneum . They r and omly received either 200 mg of intraperitoneal lidocaine or sterile saline ( 0.9 % ) . Pain scores on the first and fifteenth postoperative days were recorded and followed up every 2 weeks up to 8 months after surgery . Results Overall incidence and pain scores of epigastric and global abdominal pain were more frequent in the controls than in the lidocaine group . The incidence of persistent postcesarean pain after 8 months dropped from 20.8.0 % to 10.8 % ( P<0.001 ) when intraperitoneal lidocaine was instilled . Conclusions Intraperitoneal instillation of 200 mg of lidocaine decreased the incidence and scores of postcesarean pain when the parietal peritoneum was sutured . Further studies in a setting offering more effective acute pain control protocol s , preferably with patient-controlled analgesia , are recommended to assess the use of lidocaine before it can be widely practice Objectives Chronic postthoracotomy pain is the most common long-term complication that occurs after a thoracotomy with a reported incidence of up to 80 % . Although thoracic epidural analgesia is a widely used method for managing acute postthoracotomy pain , its effects seems question able . The objective of this prospect i ve , double-blinded , r and omized , controlled trial was to assess the effect of preemptive low-dose epidural ketamine in addition to preemptive thoracic epidural analgesia on the incidence of chronic postthoracotomy pain . Methods We analyzed 133 patients who were r and omized to preemptive thoracic epidural analgesia either with or without ketamine ( Group K : 0.12 % levobupivacaine , 2 & mgr;g/mL of fentanyl , 0.2 mg/mL ketamine , total volume of 500 mL vs. Group KF : 0.12 % levobupivacaine , 2 & mgr;g/mL of fentanyl , total volume of 500 mL ) . Pain at the thoracotomy scar site during rest and movement ( coughing ) was assessed at 2 weeks and 3 months after surgery using a visual analog scale . The incidence of allodynia and numbness was also evaluated . Results There was no difference in the incidence of chronic postthoracotomy pain at 3 months between the 2 groups ( 67.7 % in group K vs. 75 % in group KF ) . The incidences of allodynia or numbness were not different between the 2 groups . Discussion The addition of preemptive low-dose epidural ketamine ( 1.2 mg/h ) to preemptive thoracic epidural analgesia did not have any beneficial effects in preventing chronic postthoracotomy pain Background . Sternotomy causes considerable postoperative pain and postoperative pain management encompasses different analgesic regimens . In this study , we aim ed to investigate the effect of peroperative parasternal block with levobupivacaine on acute and chronic pain after coronary artery bypass graft surgery . Material s and Methods . A total of 81 patients undergoing coronary artery bypass graft surgery were included in this study . Patients were r and omly allocated by opening an envelope to receive either parasternal block with pharmacologic analgesia ( group P ; before sternal wire placement : sternotomy and mediastinal tube sites were infiltrated with local anesthetics ) or pharmacologic analgesia alone ( group C ) for postoperative pain relief . All patients received intravenous tramadol with patient-controlled analgesia at the end of the surgery . Demographic characteristics , vital signs , tramadol consumption , analgesic intake , and intensity of pain with a visual analogue scale were recorded for each patient . Six months after surgery , the patients ’ type of chronic pain was evaluated using the Leeds Assessment Neuropathic Symptoms and Signs pain scale question naire . Results . Patients who received parasternal block experienced less pain and needed less opioid analgesic ( 125.75 ± 28.9 mg in group P vs 213.17 ± 61.25 mg in group C ) for 24 hours postoperatively ( P < .001 ) . There was no significant difference in nociceptive and neuropathic pain between the groups . Conclusion . Parasternal block had a benefical effect on the management of postoperative acute pain and decreased opioid consumption after surgery but had no significant effect in chronic post surgical pain |
13,866 | 23,349,672 | Conclusions / Significance Chinese heritage clinical research participants value personal benefit , financial incentives , the ability to help others , recommendations of others , advertisements , and convenience when considering clinical research participation . | Background Subjects of Chinese heritage have been found to participate in clinical research at lower rates than other groups despite growing in numbers as a population .
While much research has examined research participants ' motivation , there has not been a comprehensive synthesis of this information with respect to participants of Chinese descent .
We sought to identify the factors that promote and hinder participation in clinical research among participants of Chinese heritage . | STUDY OBJECTIVE Emergency department ( ED ) -based clinical research has the potential to include patient population s that are typically underrepresented in clinical research . The objective of this study is to assess how emergency clinical care and research processes , informed consent , and patient demographic factors ( age , sex , and ethnicity/race ) affect enrollment and consent in clinical research in the ED . METHODS This was an analysis of prospect ively collected data of all patients ( aged 2 to 101 years ) eligible for one of 7 clinical research studies from February 2005 to April 2007 in an academic ED . We measured rates of enrollment and consent in the clinical studies . RESULTS One thous and two hundred two of the 4418 patients screened for participation in 7 clinical studies were clinical ly eligible for enrollment . Of the 868 patients who were able to provide a voluntary decision regarding consent , 639 ( 73.6 % ) agreed to participate ; an overall enrollment rate of 53.2 % . The mean age of patients enrolled was 51.8 years ( range 3 to 98 years ) . Black patients ( 49.2 % enrollment ) and Latino patients ( 18.4 % enrollment ) were less likely to be enrolled in comparison with white patients ( 58.3 % enrollment ) ( adjusted odds ratio [ OR ] of enrollment for blacks=0.64 ; 95 % confidence interval [ CI ] 0.50 to 0.82 ; adjusted OR of enrollment for Latinos=0.16 ; 95 % CI 0.08 to 0.33 ) . Enrollment rates were lower among pediatric ( 40.0 % ) and geriatric patients ( 49.1 % ) in comparison with adult patients ages 18 to 64 years ( 55.5 % ) ( adjusted OR of enrollment for pediatric patients = 0.70 , 95 % CI 0.34 to 1.43 ; adjusted OR of enrollment for geriatric patients = 0.69 , 95 % CI 0.53 to 0.90 ) . Unique issues contributing to underenrollment included challenges in consent among pediatric and elderly patients , language issues in Latino patients , reduced voluntary consent rates among black patients , and perhaps underuse of minimal risk waivers . CONCLUSION In a large academic ED , minority , pediatric , and geriatric patients were less likely to be enrolled in acute care clinical research studies than middle-aged whites . Enrollment and consent strategies design ed to enhance research participation in these important patient population s may be necessary to address disparities in the development and application of evidence -based emergency and acute care Background Concerns have been raised about low participation rates of people from minority ethnic groups in clinical trials . However , the evidence is unclear as many studies do not report the ethnicity of participants and there is insufficient information about the reasons for in eligibility by ethnic group . Where there are data , there remains the key question as to whether ethnic minorities more likely to be ineligible ( e.g. due to language ) or decline to participate . We have addressed these questions in relation to the Birmingham Rehabilitation Uptake Maximisation ( BRUM ) study , a r and omized controlled trial ( RCT ) comparing a home-based with a hospital-based cardiac rehabilitation programme in a multi-ethnic population in the UK . Methods Analysis of the ethnicity , age and sex of presenting and recruited subjects for a trial of cardiac rehabilitation in the West-Midl and s , UK . Participants : 1997 patients presenting post-myocardial infa rct ion , percutaneous transluminal coronary angioplasty or coronary artery bypass graft surgery . Data collected : exclusion rates , reasons for exclusion and reasons for declining to participate in the trial by ethnic group . Results Significantly more patients of South Asian ethnicity were excluded ( 52 % of ' South Asian ' v 36 % ' White European ' and 36 % ' Other ' , p < 0.001 ) . This difference in eligibility was primarily due to exclusion on the basis of language ( i.e. the inability to speak English or Punjabi ) . Of those eligible , similar proportions were recruited from the different ethnic groups ( white , South Asian and other ) . There was a marked difference in eligibility between people of Indian , Pakistani or Bangladeshi origin . Conclusion Once eligible for this trial , people from different ethnic groups were recruited in similar proportions . The reason for in eligibility in the BRUM study was the inability to support the range of minority language PURPOSE Well-conducted cancer clinical trials are essential for improving patient outcomes . Unfortunately , only 3 % of new cancer patients participate in clinical trials . Barriers to patient accrual in cancer clinical trials must be identified and overcome to increase patient participation . MATERIAL S AND METHODS We prospect ively tracked factors that potentially affected patient accrual into cancer clinical trials at the University of California Davis Cancer Center . Oncologists seeing new out patients were asked to complete question naires regarding patient characteristics and the physician 's decision-making on patient eligibility , protocol availability , and patient opinions on participation . Statistical analysis was performed to correlate these parameters with subsequent protocol accrual . RESULTS There were 276 assessable patients . At the initial visits , physicians did not consider clinical trials in 38 % ( 105/276 ) of patients principally because of a perception of protocol unavailability and poor performance status . Physicians considered 62 % ( 171/276 ) of patients for participation in clinical trials . Of these , only 53 % ( 91/171 ) had an appropriate protocol available for site and stage of disease . Seventy-six of 90 patients ( 84 % ) with available protocol s met eligibility criteria for a particular study . Only 39 of 76 patients ( 51 % ) agreed to participate in cancer clinical trials , for an overall accrual rate of 14 % ( 39/276 ) . The remainder ( 37/76 , 49 % ) declined trial participation despite meeting eligibility criteria . The most common reasons were a desire for other treatment ( 34 % ) , distance from the cancer center ( 13 % ) , patient refusal to disclose reason ( 11 % ) , and insurance denial ( 8 % ) . Patients with private insurance were less likely to enroll in clinical trials compared to those with government-funded insurance ( OR , 0.34 ; P = .03 ; 95 % CI , 0.13 to 0.9 ) . CONCLUSION Barriers to cancer clinical trial accrual can be prospect ively identified and addressed in the development and conduct of future studies , which may potentially lead to more robust clinical trials enrollment . Investigation of patient perceptions regarding the clinical trials process and the role of third party-payers is warranted Background / Aims : Asian Americans have been underrepresented in cancer research . The purpose of this study was to evaluate the efficacy of a multiple arm recruitment approach in improving Asian recruitment into the Cancer Genetics Network ( CGN ) . Methods : 1,096 potential participants , identified through cancer registries located at University of California , Irvine ( UCI ) and Fred Hutchinson Cancer Research Center ( FHCRC ) , were r and omly assigned to receive one of four recruitment approaches . Results : A 6.2 % gain in Asian participation into the CGN was achieved over a 2-year period at FHCRC and UCI , which contributed a 2 % CGN-wide increase in overall Asian enrollment . Site-specific differences in recruitment success by study arm were observed . Conclusion : Novel recruitment approaches can assist in improving recruitment of Asian population s into cancer genetic research studies PURPOSE R and om assignment to clinical trials involving different treatment modalities can be difficult . We describe our experience with the Surgical Prostatectomy Versus Interstitial Radiation Intervention Trial ( SPIRIT ; ACOSOG Z0070 NCIC PR10 ) , a r and omized trial for early-stage prostate cancer comparing radical prostatectomy ( RP ) , and brachytherapy ( BT ) . A multidisciplinary educational session was developed to improve patient underst and ing of treatment options and to facilitate accrual . PATIENTS AND METHODS Prostate cancer referrals were screened and men who met favorable risk criteria ( T1c/T2a , prostate-specific antigen [ PSA ] < 10 ng/mL , Gleason < or = 6 ) were invited to a structured education session before a specialty consultation . Men and their partners viewed the SPIRIT informed-consent video and heard from a cancer patient who described his participation in a r and omized trial . Then , a urologist and radiation oncologist together compared and contrasted RP and BT to establish the rationale for the trial . RESULTS In May 2002 , SPIRIT opened for accrual and was endorsed by the University Health Network urologists and radiation oncologists . The first 27 eligible patients were approached about SPIRIT , consulted both specialties , and viewed an educational video . No patients consented . The multidisciplinary education session was then introduced . Forty-seven education sessions with 263 patients result ed in 34 consents . Of 203 patients who were suitable for the study but declined r and om assignment , 62 chose surgery , 94 chose brachytherapy , three patients chose external radiotherapy , and 11 chose no treatment . Consent rates for eligible and suitable patients were one in six . CONCLUSION Men who underst and their treatment options and trial rationale as presented jointly by representative specialists from competing treatment modalities may be better equipped to make an informed decision and are more likely to consent to r and om assignment Purpose Writing scientific articles is a daunting task for novice research ers . In this qualitative study carried out in 2007 , the authors evaluated the experiences of a group of novice research ers engaged in the writing process , to eluci date the main difficulties and sources of encouragement they encountered . Method Sixteen novice research ers were interviewed . Most were women ( 10 ) , and most were enrolled in programs of medicine ( 9 ) , followed by nursing ( 4 ) and physical therapy ( 3 ) . These were drawn via convenience sampling from a r and omized control trial in which 48 of them were equally assigned to either an online or a face-to-face course of instruction . On completion , interviews were conducted in focus groups of four students each . The interviews were transcribed and read independently by two of the authors , who then encoded the material based on the principles of grounded theory . Initial categories were converted to major emerging themes , which were vali date d when participants were asked to review the findings . Triangulation of results was carried out by discussing the emerging themes in an online forum with five specialists in college writing education . Results Classifying the diverse responses of participants led to the emergence of four major themes : cognitive burden , group support and mentoring , difficulty in distinguishing between content and structure , and backward design of manuscripts . Conclusions The themes produced by this study provide some insight into the challenges faced by novice research ers in their early attempts at scientific writing . Remedies that address these challenges are needed to substantially improve scientific writing instruction PURPOSE To investigate patients ' willingness to participate ( WTP ) in a r and omized controlled trial ( RCT ) comparing intensity-modulated radiotherapy ( IMRT ) with proton beam therapy ( PBT ) for prostate cancer ( PCa ) . METHODS AND MATERIAL S We undertook a qualitative research study in which we prospect ively enrolled patients with clinical ly localized PCa . We used purposive sampling to ensure a diverse sample based on age , race , travel distance , and physician . Patients participated in a semi-structured interview in which they review ed a description of a hypothetical RCT , were asked open-ended and focused follow-up questions regarding their motivations for and concerns about enrollment , and completed a question naire assessing characteristics such as demographics and prior knowledge of IMRT or PBT . Patients ' stated WTP was assessed using a 6-point Likert scale . RESULTS Forty-six eligible patients ( 33 white , 13 black ) were enrolled from the practice s of eight physicians . We identified 21 factors that impacted patients ' WTP , which largely centered on five major themes : altruism/desire to compare treatments , r and omization , deference to physician opinion , financial incentives , and time dem and s/scheduling . Most patients ( 27 of 46 , 59 % ) stated they would either " definitely " or " probably " participate . Seventeen percent ( 8 of 46 ) stated they would " definitely not " or " probably not " enroll , most of whom ( 6 of 8) preferred PBT before their physician visit . CONCLUSIONS A substantial proportion of patients indicated high WTP in a RCT comparing IMRT and PBT for PCa Study objectives The emergency department ( ED ) provides an arena for patient enrolment into a variety of research studies even for non-critically ill patients . Given the types of illness , time constraints and sense of urgency that exists in the ED environment , concern exists about whether research subjects in the ED can provide full consent for participation . We sought to identify enrolled research subjects ' perspectives on the informed consent process for research conducted in the ED . Methods This was a prospect i ve , observational study of ED subjects , 18 years or older , who had been approached to participate in research in the ED and who were judged to have decision-making capacity . Exclusions were critical illness and refusal to participate . Subjective were followed up within 1 week after enrolling using structured phone interviews by trained interviewers . Results During the study period , 229 eligible patients were approached to participate in both a target study and this study . Of these , 66 % ( 150/229 ) agreed to participate in this study , at least to the extent of allowing us access to their demographic data . The study participant group was similar in terms of gender to this particular ED 's patient population but had significantly more African-Americans and persons older than 45 . Conclusion Despite rigorous time constraints and rapid throughput times , the majority of subjects who consented to research participation in the ED felt that they were sufficiently informed and had adequate time to decide to participate PURPOSE To design and test a geriatric educational intervention to improve accrual of cancer patients age 65 years and older to cooperative group-sponsored treatment trials . METHODS Main member institutions of the Cancer and Leukemia Group B ( CALGB ) and its affiliates were r and omly assigned to receive st and ard information ( n = 73 ) or educational intervention ( n = 53 ) . St and ard information included CALGB Web site access and periodic notification about existing trials . The geriatric educational intervention included st and ard information plus : ( 1 ) an educational seminar ; ( 2 ) educational material s ; ( 3 ) a list of available protocol s for use on charts ; ( 4 ) a monthly e-mail and mail reminders for 1 year ; and ( 5 ) a case discussion seminar . The main outcome was percentage of accrual of older persons to phase II and III treatment protocol s after study initiation compared with baseline . RESULTS There were 3,032 patients entered onto trials in the baseline year , and 2,160 and 1,239 during the 2 years postintervention , respectively . Overall percentage of accrual of older patients was 37 % at baseline , and 33 % and 31 % during the first and second years after intervention . There was no improvement in accrual in the intervention versus control arm : 36 % v 32 % in the first year and 31 % v 31 % in the second year . CONCLUSION Accrual of older patients was not increased by this intervention . Reasons for lack of effect include low intervention intensity , high baseline accrual rates , and closure of several high-accruing protocol s during the study . More intense and multifaceted approaches will be needed to change physician ( and patient ) behavior and to increase accrual of older persons to clinical trials |
13,867 | 10,796,845 | Subgroup analyses suggest that the benefits may be confined to people with no occult choroidal neovascularisation .
REVIEW ER 'S CONCLUSIONS Photodynamic therapy in people with classic choroidal neovascularisation due to age-related macular degeneration is effective in preventing visual loss .
There is no evidence that photodynamic therapy is beneficial for people with evidence of occult choroidal neovascularisation . | BACKGROUND In neovascular age-related macular degeneration , new vessels grow under the retina , distorting vision and leading to scarring .
This is further exacerbated if the blood vessels leak .
Photodynamic therapy , originally used in cancer treatment , has been investigated as a way to treat the neovascular membranes without affecting the retina .
OBJECTIVES The aim of this review is to examine the evidence for the safety and effectiveness of photodynamic therapy in the treatment of neovascular age-related macular degeneration . | PURPOSE To determine if photodynamic therapy with verteporfin ( Visudyne ; Novartis AG , Bülach , Switzerl and ) , termed verteporfin therapy , can safely reduce the risk of vision loss compared with a placebo ( with sham treatment ) in patients with subfoveal choroidal neovascularization caused by age-related macular degeneration who were identified with a lesion composed of occult with no classic choroidal neovascularization , or with presumed early onset classic choroidal neovascularization with good visual acuity letter score . METHODS This was a double-masked , placebo-controlled ( sham treatment ) , r and omized , multicenter clinical trial involving 28 ophthalmology practice s in Europe and North America . The study population was patients with age-related macular degeneration , with subfoveal choroidal neovascularization lesions measuring no greater than 5400 microm in greatest linear dimension with either 1 ) occult with no classic choroidal neovascularization , best-corrected visual acuity score of at least 50 ( Snellen equivalent approximately 20/100 ) , and evidence of hemorrhage or recent disease progression ; or 2 ) evidence of classic choroidal neovascularization with a best-corrected visual acuity score of at least 70 ( better than a Snellen equivalent of approximately 20/40 ) ; assigned r and omly ( 2:1 ) to verteporfin therapy or placebo therapy . Verteporfin ( 6 mg per square meter of body surface area ) or placebo ( 5 % dextrose in water ) was administered by means of intravenous infusion of 30 ml over 10 minutes . Fifteen minutes after the start of the infusion , a laser light at 689 nm delivered 50 J/cm(2 ) by application of an intensity of 600 mW/cm(2 ) over 83 seconds using a spot size with a diameter 1000 microm larger than the greatest linear dimension of the choroidal neovascularization lesion on the retina . At follow-up examinations every 3 months , retreatment with the same regimen was applied if angiography showed fluorescein leakage . The main outcome measure was at least moderate vision loss , that is , a loss of at least 15 letters ( approximately 3 lines ) , adhering to an intent-to-treat analysis with the last observation carried forward to impute for missing data . RESULTS Two hundred ten ( 93 % ) and 193 ( 86 % ) of the 225 patients in the verteporfin group compared with 104 ( 91 % ) and 99 ( 87 % ) of the 114 patients in the placebo group completed the month 12 and 24 examinations , respectively . On average , verteporfin-treated patients received five treatments over the 24 months of follow-up . The primary outcome was similar for the verteporfin-treated and the placebo-treated eyes through the month 12 examination , although a number of secondary visual and angiographic outcomes significantly favored the verteporfin-treated group . Between the month 12 and 24 examinations , the treatment benefit grew so that by the month 24 examination , the verteporfin-treated eyes were less likely to have moderate or severe vision loss . Of the 225 verteporfin-treated patients , 121 ( 54 % ) compared with 76 ( 67 % ) of 114 placebo-treated patients lost at least 15 letters ( P = .023 ) . Likewise , 67 of the verteporfin-treated patients ( 30 % ) compared with 54 of the placebo-treated patients ( 47 % ) lost at least 30 letters ( P = .001 ) . Statistically significant results favoring verteporfin therapy at the month 24 examination were consistent between the total population and the subgroup of patients with a baseline lesion composition identified as occult choroidal neovascularization with no classic choroidal neovascularization . This subgroup included 166 of the 225 verteporfin-treated patients ( 74 % ) and 92 of the 114 placebo-treated patients ( 81 % ) . In these patients , 91 of the verteporfin-treated group ( 55 % ) compared with 63 of the placebo-treated group ( 68 % ) lost at least 15 letters ( P = .032 ) , whereas 48 of the verteporfin-treated group ( 29 % ) and 43 of the placebo-treated group ( 47 % ) lost at least 30 letters ( P = .004 ) . Other secondary outcomes , including visual acuity letter score worse than 34 ( approximate Snellen equivalent of 20/200 or worse ) , mean change in visual acuity letter score , development of classic choroidal neovascularization , progression of classic choroidal neovascularization and size of lesion , favored the verteporfin-treated group at both the month 12 and month 24 examination for both the entire study group and the subgroup of cases with occult with no classic choroidal neovascularization at baseline . Subgroup analyses of lesions composed of occult with no classic choroidal neovascularization at baseline suggested that the treatment benefit was greater for patients with either smaller lesions ( 4 disc areas or less ) or lower levels of visual acuity ( letter score less than 65 , an approximate Snellen equivalent of 20/50(-1 ) or worse ) at baseline . Prospect ively planned multivariable analyses confirmed that these two baseline variables affected the magnitude of treatment benefit . ( ABSTRACT TRUNCATED OBJECTIVE To report 24-month vision and fluorescein angiographic outcomes from trials evaluating photodynamic therapy with verteporfin ( Visudyne ; CIBA Vision Corp , Duluth , Ga ) in patients with subfoveal choroidal neovascularization ( CNV ) caused by age-related macular degeneration ( AMD ) . DESIGN Two multicenter , double-masked , placebo-controlled , r and omized clinical trials . SETTING Twenty-two ophthalmology practice s in Europe and North America . PARTICIPANTS Patients with subfoveal CNV lesions caused by AMD with greatest linear dimension on the retina measuring 5400 micrometer or less , with evidence of classic CNV and best-corrected visual acuity ( approximate Snellen equivalent ) between 20/40 and 20/200 . METHODS The methods were similar to those described in our 1-year results , with follow-up examinations beyond 1 year continuing every 3 months ( except for Photograph Reading Center evaluations , which occurred only at month 18 and month 24 examinations ) . During the second year , the same regimen ( with verteporfin or placebo as applied at baseline ) was used if angiography showed fluorescein leakage from CNV . The primary outcome was the proportion of eyes with fewer than 15 letters ( approximately 3 lines ) of visual acuity loss at the month 24 examination , adhering to an intent-to-treat analysis . The last observation was carried forward to impute for any missing data . RESULTS Three hundred fifty-one ( 87 % ) of 402 patients in the verteporfin group compared with 178 ( 86 % ) of 207 patients in the placebo group completed the month 24 examination . Beneficial outcomes with respect to visual acuity and contrast sensitivity noted at the month 12 examination in verteporfin-treated patients were sustained through the month 24 examination . At the month 24 examination for the primary outcome , 213 ( 53 % ) of 402 verteporfin-treated patients compared with 78 ( 38 % ) of 207 placebo-treated patients lost fewer than 15 letters ( P<.001 ) . In subgroup analyses for predominantly classic lesions ( in which the area of classic CNV makes up at least 50 % of the area of the entire lesion ) at baseline , 94 ( 59 % ) of 159 verteporfin-treated patients compared with 26 ( 31 % ) of 83 placebo-treated patients lost fewer than 15 letters at the month 24 examination ( P<.001 ) . For minimally classic lesions ( in which the area of classic CNV makes up < 50 % but > 0 % of the area of the entire lesion ) at baseline , no statistically significant differences in visual acuity were noted . Few additional photosensitivity adverse reactions and injection site adverse events were associated with verteporfin therapy in the second year of follow-up . CONCLUSIONS The visual acuity benefits of verteporfin therapy for AMD patients with predominantly classic CNV subfoveal lesions are safely sustained for 2 years , providing more compelling evidence to use verteporfin therapy for these cases . For AMD patients with subfoveal lesions that are minimally classic , there is insufficient evidence to warrant routine use of verteporfin therapy OBJECTIVE To report vision and safety outcomes from an extension of a 2-year investigation evaluating verteporfin photodynamic therapy in patients with age-related macular degeneration with subfoveal choroidal neovascularization ( CNV ) . DESIGN AND SETTING Open-label extension of selected patients from 2 multicenter , double-masked , placebo-controlled , r and omized clinical trials , the Treatment of Age-Related Macular Degeneration With Photodynamic Therapy ( TAP ) Investigation , at 22 ophthalmology practice s in Europe and North America . PARTICIPANTS Patients enrolled in the TAP Investigation and followed up for at least 24 months in whom verteporfin therapy to CNV might reduce the risk of further vision loss . METHODS Before receiving verteporfin therapy in the extension , eligible patients signed a written informed consent form accompanied by an oral consent process approved by local institutional review boards . Methods were similar to those described for 1- and 2-year results , with follow-up examinations beyond 2 years continuing at 3-month intervals with a few exceptions , including that extension patients with fluorescein leakage from CNV were to receive open-label verteporfin therapy irrespective of their original treatment assignment . RESULTS Of 402 patients in the verteporfin group , 351 ( 87.3 % ) completed the month 24 examination ; 320 ( 91.2 % ) of these enrolled in the extension study . The enrolled participants included 124 ( 78.0 % ) of the 159 verteporfin-treated patients with lesions composed of predominantly classic CNV at baseline , of whom 105 ( 84.7 % ) completed the month 36 examination . Verteporfin-treated patients with this lesion composition at baseline who participated in the extension study , with or without a month 36 examination , appeared more likely to have a younger age , better level of visual acuity , absence of fluorescein leakage from classic CNV , or no progression of classic CNV beyond the baseline boundaries of the lesion at the month 24 examination compared with those who did not enroll in the extension . For the 105 patients with a predominantly classic baseline lesion composition who completed the month 36 examination , an average of 1.3 treatments were given from the month 24 examination up to , but not including , the month 36 examination . A letter score loss in the study eye of at least 15 from baseline for these patients occurred in 39 ( 37.5 % ) at the month 24 examination compared with 44 ( 41.9 % ) of these patients at the month 36 examination . Visual acuity changed little from the month 24 examination ( mean , -1.9 lines ) to the month 36 examination ( mean , -2.0 lines ) for these eyes . Verteporfin-treated patients had little change in the mean visual acuity lost and few or no additional instances of infusion-related back pain or photosensitivity reactions from month 24 to month 36 . Two patients originally assigned to placebo had acute severe vision decrease within 7 days after verteporfin treatment during the extension . One patient originally assigned to verteporfin had acute severe vision decrease after verteporfin treatment of the fellow eye during the extension . CONCLUSIONS Vision outcomes for verteporfin-treated patients with predominantly classic lesions at baseline remained relatively stable from month 24 to month 36 , although only approximately one third of the verteporfin-treated patients originally enrolled with this lesion composition had a month 36 examination . From these results , the TAP Study Group identified no safety concerns to preclude repeating photodynamic therapy with verteporfin . Additional treatment was judged likely to reduce the risk of further vision loss . Caution appears warranted in the absence of comparison with an untreated group during the extension and since not all patients in the TAP Investigation participated in the TAP Extension OBJECTIVE To determine if photodynamic therapy with verteporfin ( Visudyne ; CIBA Vision Corp , Duluth , GA ) can improve the chance of stabilizing or improving vision ( < 8 letter loss ) safely in patients with subfoveal choroidal neovascularization ( CNV ) caused by pathologic myopia . DESIGN Multicenter , double-masked , placebo-controlled , r and omized clinical trial at 28 ophthalmology practice s in Europe and North AMERICA : PARTICIPANTS One hundred twenty patients with subfoveal CNV caused by pathologic myopia with a greatest linear dimension no more than 5400 microM and best-corrected visual acuity ( Snellen equivalent ) of approximately 20/100 or better . INTERVENTION Patients were r and omly assigned ( 2:1 ) to verteporfin ( 6 mg per square meter of body surface area ; n = 81 ) or placebo ( 5 % dextrose in water ; n = 39 ) administered via intravenous infusion of 30 ml over 10 minutes . Fifteen minutes after the start of the infusion , a laser light at 689 nm was delivered at an intensity of 600 mW/cm(2 ) over 83 seconds to give a light dose of 50 J/cm(2 ) to a round spot size on the retina with a diameter of 1000 , microM larger than the greatest linear dimension of the choroidal neovascular lesion . At follow-up examinations every 3 months , retreatment with either verteporfin or placebo ( as assigned at baseline ) was applied to areas of fluorescein leakage if present . MAIN OUTCOME MEASURES The primary outcome was the proportion of eyes at the follow-up examination 12 months after study entry with fewer than eight letters ( approximately 1.5 lines ) of visual acuity lost , adhering to an intent-to-treat analysis . RESULTS At baseline , more than 90 % of each group had evidence of classic CNV ( regardless of whether occult CNV was present ) and only 12 ( 15 % ) and 5 ( 13 % ) cases in the verteporfin and placebo groups , respectively , had occult CNV ( regardless of whether classic CNV was present ) . Seventy-nine of the 81 verteporfin-treated patients ( 98 % ) compared with 36 of the 39 placebo-treated patients ( 92 % ) completed the month 12 examination . Visual acuity , contrast sensitivity , and fluorescein angiographic outcomes were better in the verteporfin-treated eyes than in the placebo-treated eyes at every follow-up examination through the month 12 examination . At the month 12 examination , 58 ( 72 % ) of the verteporfin-treated patients compared with 17 ( 44 % ) of the placebo-treated patients lost fewer than eight letters ( P < 0.01 ) , including 26 ( 32 % ) versus 6 ( 15 % ) improving at least five letters ( > /=1 line ) . Seventy ( 86 % ) of the verteporfin-treated patients compared with 26 ( 67 % ) of the placebo-treated patients lost fewer than 15 letters ( P = 0.01 ) . Few ocular or other systemic adverse events were associated with verteporfin therapy compared with placebo treatment . CONCLUSIONS Because photodynamic therapy with verteporfin can safely increase the chance of stabilizing or improving vision in patients with subfoveal CNV from pathologic myopia compared with a placebo , we recommend ophthalmologists consider verteporfin therapy for treatment of such patients Background In the Treatment of Age-Related Macular Degeneration With Photodynamic Therapy ( TAP ) investigation , verteporfin therapy reduced the risk of at least moderate vision loss ( defined as a loss of at least 15 letters of visual acuity ) in patients with subfoveal choroidal neovascularization ( CNV ) secondary to age-related macular degeneration ( ARMD ) . This report presents detailed analyses of 24-month contrast sensitivity outcomes in these patients . Methods The patients included in the TAP investigation had subfoveal CNV secondary to ARMD and received verteporfin therapy ( n = 402 ) or placebo ( n = 207 ) at the first visit , with retreatment at each 3-month follow-up visit if angiography revealed fluorescein leakage from CNV . Contrast sensitivity was determined at each visit using a Pelli – Robson chart . Results At the month 24 examination , verteporfin-treated patients were less likely to lose at least 6 or 15 letters of contrast sensitivity than placebo-treated patients ( 86 [ 21 % ] versus 94 [ 45 % ] , and 27 [ 7 % ] versus 24 [ 12 % ] , respectively;P < 0.05 for both comparisons ) . The superiority of verteporfin therapy over placebo was greater in patients with predominantly classic CNV at baseline , although verteporfin-treated patients with minimally classic CNV also had better contrast sensitivity outcomes . Conclusions Consistent with visual acuity outcomes , verteporfin therapy reduced the risk of a clinical ly relevant loss of contrast sensitivity in the total study population , with the greatest effect in patients with predominantly classic subfoveal CNV secondary to ARMD . Verteporfin-treated patients with minimally classic CNV also had better contrast sensitivity outcomes than patients who received placebo . Given the association between contrast sensitivity and visual disability , the beneficial effects of verteporfin therapy on contrast sensitivity outcomes are expected to have a favorable impact on patients ’ daily activities PURPOSE To determine if oral hydration decreases the incidence of verteporfin infusion-associated pain and to find out if other factors play a role in predisposing to this undesired complication . METHODS Nonr and omized clinical trial . We prospect ively examined 250 consecutive patients who have been diagnosed with subfoveal choroidal neovascularization secondary to age-related macular degeneration and received photodynamic therapy using verteporfin . One hundred twenty-five patients were assigned to receive 500 ml of water orally administered 30 minutes before beginning the verteporfin infusion , and the remaining 125 consecutive patients were used as controls . Historical and clinical factors in these patients were evaluated for their association with the presence of verteporfin infusion-associated pain . RESULTS Out of 125 patients receiving water before treatment 12 ( 9.6 % ) experienced verteporfin infusion-associated pain . Among the 125 patients who did not get hydration before therapy 12(9.6 % ) experienced verteporfin infusion-associated pain . There was no statistical difference between the incidence of pain in the two groups ( P = 1.0 ) . No statistically significant association was evidence d between the presence of pain and participant 's baseline characteristics , except for pain on previous administration of verteporfin ( P < .001 ) . Out of 250 total patients 24 ( 9.6 % ) developed verteporfin infusion-associated pain . Back pain was the most common and occurred in 21 ( 8.4 % ) patients , but other sites included leg , groin , chest , buttock , arm , and shoulder pain concurrently or independently . All patients had resolution of their pain , including chest pain , on cessation of the infusion . CONCLUSIONS Verteporfin infusion-associated pain may be more common than has been previously reported and is not limited to the back area . It appears to be an idiosyncratic reaction to the drug . It does not seem to be prevented by oral hydration before infusion of verteporfin , and no baseline characteristics , other than a history of pain on previous infusion , seem to be predictive of verteporfin infusion-associated pain |
13,868 | 16,034,853 | Allocation to hospital at home result ed in a small reduction in hospital length of stay , but hospital at home increased overall length of care .
Patients allocated to hospital at home expressed greater satisfaction with care than those in hospital , while the view of carers was mixed .
Early discharge schemes for patients recovering from elective surgery and elderly patients with a medical condition may have a place in reducing the pressure on acute hospital beds , providing the views of the carers are taken into account .
For these clinical groups hospital length of stay is reduced , although this is offset by the provision of hospital at home . | BACKGROUND Hospital at home is defined as a service that provides active treatment by health care professionals , in the patient 's home , of a condition that otherwise would require acute hospital in-patient care , always for a limited period .
OBJECTIVES To assess the effects of hospital at home compared with in-patient hospital care . | Abstract Objectives : To examine the cost of providing hospital at home in place of some forms of inpatient hospital care . Design : Cost minimisation study within a r and omised controlled trial . Setting : District general hospital and catchment area of neighbouring community trust . Subjects : Patients recovering from hip replacement ( n=86 ) , knee replacement ( n=86 ) , and hysterectomy ( n=238 ) ; elderly medical patients ( n=96 ) ; and patients with chronic obstructive airways disease ( n=32 ) . Interventions : Hospital at home or inpatient hospital care . Main outcome measures : Cost of hospital at home scheme to health service , to general practitioners , and to patients and their families compared with hospital care . Results : No difference was detected in total healthcare costs between hospital at home and hospital care for patients recovering from a hip or knee replacement , or elderly medical patients . Hospital at home significantly increased healthcare costs for patients recovering from a hysterectomy ( ratio of geometrical means 1.15 , 95 % confidence interval 1.04 to 1.29 , P=0.009 ) and for those with chronic obstructive airways disease ( Mann-Whitney U test , P=0.01 ) . Hospital at home significantly increased general practitioners ' costs for elderly medical patients ( Mann-Whitney U test , P<0.01 ) and for those with chronic obstructive airways disease ( P=0.02 ) . Patient and carer expenditure made up a small proportion of total costs . Conclusion : Hospital at home care did not reduce total healthcare costs for the conditions studied in this trial , and costs were significantly increased for patients recovering from a hysterectomy and those with chronic obstructive airways disease . There was some evidence that costs were shifted to primary care for elderly medical patients and those with chronic obstructive airways disease . Key messages Hospital at home schemes are a popular alternative to st and ard hospital care , but there is uncertainty about their cost effectiveness In our r and omised controlled trial we compared the cost of hospital at home care with that of inpatient hospital care for patients recovering from hip replacement , knee replacement , and hysterectomy ; elderly medical patients ; and those with chronic obstructive airways disease There were no major differences in health service costs between the two arms of the trial for patients recovering from hip or knee replacement and elderly medical patients Hospital at home care increased healthcare costs for patients recovering from hysterectomy and for those with chronic obstructive airways disease Hospital at home care result ed in some costs shifting to general practitioners for elderly medical patients and those with chronic obstructive airways OBJECTIVE : To test the cost effectiveness of Hospital in the Home compared to hospital admission for acute medical conditions BACKGROUND We have previously reported the use of a hospital based respiratory nurse service ( Acute Respiratory Assessment Service , ARAS ) to support home treatment of patients with exacerbations of chronic obstructive pulmonary disease ( COPD ) . A controlled trial was undertaken to compare early discharge with home treatment supported by respiratory nurses with conventional hospital management of patients admitted with exacerbations of COPD . METHODS Patients with COPD admitted as emergencies were identified the next working day . They were eligible for inclusion in the study if the differential diagnosis included an exacerbation of COPD , but were excluded if other medical conditions or acidotic respiratory failure required inpatient investigation or management . Of 360 patients review ed , 209 were being assessed for other active medical problems and were excluded , 33 potential participants were already involved in research studies and so were ineligible , and 37 did not wish to participate in the study . Eighty one patients were r and omised to receive conventional inpatient care ( n=40 ) or to planned early discharge the next working day ( n=41 ) . Those discharged early continued treatment at home under the supervision of specialist respiratory nurses . Outcome measures were readmission , additional hospital days , and deaths within 60 days of initial admission . Process measures included number of visits , duration of follow up by the respiratory nurse , and additional treatment provided to support early discharge . RESULTS On an intention to treat basis , a policy of early discharge reduced inpatient stay from a mean of 6.1 ( range 1–13 ) days with conventional management to 3.2 ( 1–16 ) days with an early discharge policy . Twelve patients ( 30 % conventional management , 29.3 % early discharge ) were readmitted in each group giving a mean difference in readmission of 0.7 % ( 95 % CI of the difference –19.2 to 20.6 ) . In the conventional management group readmitted patients spent a mean of 8.75 additional days in hospital compared with 7.83 days in the early discharge group , giving a mean difference of 0.92 days ( 95 % CI of the difference –6.5 to 8.3 ) . There were two deaths ( 5 % ) in the conventional management group and one ( 2.4 % ) in the early discharge group , a mean difference of 2.6 % ( 95 % CI of the difference –5.7 to 10.8 ) . CONCLUSIONS Patients with acute exacerbations of COPD uncomplicated by acidotic respiratory failure or other medical problems can be discharged home earlier than is current practice with support by visiting respiratory nurses . No difference was found in the subsequent need for readmission BACKGROUND Patients with acute proximal deep-vein thrombosis are usually treated first in the hospital with intravenous st and ard ( unfractionated ) heparin . However , the longer plasma half-life , better bioavailability after subcutaneous administration , and more predictable anticoagulant response of low-molecular-weight heparins make them attractive for possible home use . We compared these two approaches . METHODS Patients with acute proximal deep-vein thrombosis were r and omly assigned to receive either intravenous st and ard heparin in the hospital ( 253 patients ) or low-molecular-weight heparin ( 1 mg of enoxaparin per kilogram of body weight subcutaneously twice daily ) administered primarily at home ( 247 patients ) . The study design allowed out patients taking low-molecular-weight heparin to go home immediately and hospitalized patients taking low-molecular-weight heparin to be discharged early . All the patients received warfarin starting on the second day . RESULTS Thirteen of the 247 patients receiving low-molecular-weight heparin ( 5.3 percent ) had recurrent thromboembolism , as compared with 17 of the 253 patients receiving st and ard heparin ( 6.7 percent ; P=0.57 ; absolute difference , 1.4 percentage points ; 95 percent confidence interval , -3.0 to 5.7 ) . Five patients receiving low-molecular-weight heparin had major bleeding , as compared with three patients receiving st and ard heparin . After r and omization , the patients who received low-molecular-weight heparin spent a mean of 1.1 days in the hospital , as compared with 6.5 days for the st and ard-heparin group ; 120 patients in the low-molecular-weight- heparin group did not need to be hospitalized at all . CONCLUSIONS Low-molecular-weight heparin can be used safely and effectively to treat patients with proximal deep-vein thrombosis at home A r and omised controlled trial has been conducted into the effects of discharging patients from hospital either 48 hours or six to seven days after operations for inguinal hernia and varicose veins . There was no statistically significant difference in major postoperative complications between the two lengths of stay for either of the two conditions . Similarly there was no difference between the two groups of hernia patients in relation to eventual recurrences . There was no significant difference in length of convalescence between long-stay and short-stay patients in full-time occupations . The savings to the statutory services of discharging patients early were estimated at 25.72 pounds per patient . Patients appeared to approve of the type of care they experienced , regardless of length of stay . However , the families of short-stay patients were significantly less enthusiastic in their attitudes towards the policy of early discharge than the families of long-stay patients BACKGROUND AND PURPOSE This study describes the methodology , patient outcome , and use of hospital and rehabilitation services at 3 months of a population -based r and omized controlled trial . The purpose was to evaluate rehabilitation at home after early supported discharge from the Department of Neurology , Huddinge Hospital , for moderately disabled stroke patients in southwest Stockholm . METHODS The patients were eligible if they were continent , independent in feeding , had mental function within normal limits , and had impaired motor function and /or aphasia 1 week after stroke . Patients were r and omized either to early supported discharge with continuity of rehabilitation at home for 3 to 4 months or to routine rehabilitation service in a hospital , day care , and /or outpatient care . The home rehabilitation team consisted of two physical therapists , two occupational therapists , and one speech therapist ; one of the therapists was assigned as case manager for the patient . The rehabilitation program at home emphasized a task- and context -oriented approach . The activities were chosen on the basis of the patient 's personal interests . Spouses were offered education and individual counseling . A total of 81 patients were followed up for a minimum of 3 months . Patient outcome was assessed by the Frenchay Social Activity Index , Extended Katz Index , Barthel Index , Lindmark Motor Capacity Assessment , Nine-Hole Peg Test , walking speed over 10 m , reported falls , and subjective dysfunction according to the Sickness Impact Profile . Patient use of hospital and home rehabilitation service and patient satisfaction with care were studied . RESULTS Overall there were no statistical significant differences in outcome . Multivariate logistic regression analysis suggested a systematic positive effect for the home rehabilitation group in social activity , activities of daily living , motor capacity , manual dexterity , and walking . A considerable difference in re source use during such a 3-month period was seen . A 52 % reduction in hospitalization was observed : from 29 days in the routine rehabilitation group to 14 days in the home rehabilitation group . Patient satisfaction was in favor of the latter group . CONCLUSIONS Early supported discharge with continuity of home rehabilitation services for the majority of moderately disabled stroke patients during the first 3-month period after acute stroke is not less beneficial than routine rehabilitation and can be a rehabilitation service of choice if follow-up at 6 and 12 months confirms the suggested effectiveness and considerable reduction in use of health care It was postulated that home hospitalisation ( HH ) of selected chronic obstructive pulmonary disease ( COPD ) exacerbations admitted at the emergency room ( ER ) could facilitate a better outcome than conventional hospitalisation . To this end , 222 COPD patients ( 3.2 % female ; 71±10 yrs ( mean±sd ) ) were r and omly assigned to HH ( n=121 ) or conventional care ( n=101 ) . During HH , integrated care was delivered by a specialised nurse with the patient 's free-phone access to the nurse ensured for an 8‐week follow-up period . Mortality ( HH : 4.1 % ; controls : 6.9 % ) and hospital readmissions ( HH : 0.24±0.57 ; controls : 0.38±0.70 ) were similar in both groups . However , at the end of the follow-up period , HH patients showed : 1 ) a lower rate of ER visits ( 0.13±0.43 versus 0.31±0.62 ) ; and 2 ) a noticeable improvement of quality of life ( Δ St George 's Respiratory Question naire ( SGRQ ) , −6.9 versus −2.4 ) . Furthermore , a higher percentage of patients had a better knowledge of the disease ( 58 % versus 27 % ) , a better self-management of their condition ( 81 % versus 48 % ) , and the patient 's satisfaction was greater . The average overall direct cost per HH patient was 62 % of the costs of conventional care , essentially due to fewer days of inpatient hospitalisation ( 1.7±2.3 versus 4.2±4.1 days ) . A comprehensive home care intervention in selected chronic obstructive pulmonary disease exacerbations appears as cost effective . The home hospitalisation intervention generates better outcomes at lower costs than conventional care To compare the results of home and hospital treatment in men aged under 70 years who had suffered acute myocardial infa rct ion within 48 hours 1895 patients were considered for study in four centres in south-west Engl and . Four-hundred- and -fifty patients were r and omly allocated to receive care either at home by their family doctor or in hospital , initially in an intensive care unit . The r and omised treatment groups were similar in age , history of cardiovascular disease , and incidence of hypotension when first examined . They were followed up for up to a year after onset . The mortality rate at 28 days was 12 % for the r and om home group and 14 % for the r and om hospital group ; the corresponding figures at 330 days were 20 % and 27 % . On average , older patients and those without initial hypotension fared rather better under home care . The patients who underwent r and omisation were similar to those whose place of care was not r and omised , except that the non-r and omised group contained a higher proportion of initially hypotensive patients , whose prognosis was poor wherever treated . These results confirm and extend our preliminary findings . Home care is a proper form of treatment for many patients with acute myocardial infa rct ion , particularly those over 60 years and those with an uncomplicated attack seen by general practitioners BACKGROUND An intravenous course of st and ard ( unfractionated ) heparin with the dose adjusted to prolong the activated partial-thromboplastin time to a desired length is the st and ard initial in-hospital treatment for patients with deep-vein thrombosis , but fixed-dose subcutaneous low-molecular-weight heparin appears to be as effective and safe . Because the latter treatment can be given on an outpatient basis , we compared the two treatments in symptomatic out patients with proximal-vein thrombosis but no signs of pulmonary embolism . METHODS We r and omly assigned patients to adjusted-dose intravenous st and ard heparin administered in the hospital ( 198 patients ) or fixed-dose subcutaneous low-molecular-weight heparin administered at home , when feasible ( 202 patients ) . We compared the treatments with respect to recurrent venous thromboembolism , major bleeding , quality of life , and costs . RESULTS Seventeen of the 198 patients who received st and ard heparin ( 8.6 percent ) and 14 of the 202 patients who received low-molecular-weight heparin ( 6.9 percent ) had recurrent thromboembolism ( difference , 1.7 percentage points ; 95 percent confidence interval , -3.6 to 6.9 ) . Major bleeding occurred in four patients assigned to st and ard heparin ( 2.0 percent ) and one patient assigned to low-molecular-weight heparin ( 0.5 percent ; difference , 1.5 percentage points ; 95 percent confidence interval , -0.7 to 2.7 ) . Quality of life improved in both groups . Physical activity and social functioning were better in the patients assigned to low-molecular-weight heparin . Among the patients in that group , 35 percent were never admitted to the hospital at all , and 40 percent were discharged early . This treatment was associated with a mean reduction in hospital days of 67 percent , ranging from 29 percent to 86 percent in the various study centers . CONCLUSIONS In patients with proximal-vein thrombosis , treatment with low-molecular-weight heparin at home is feasible , effective , and safe BACKGROUND AND PURPOSE We have previously shown that treatment of acute stroke patients in our stroke unit ( SU ) compared with treatment in general ward ( GWs ) improves short- and long-term survival and functional outcome and increases the possibility of earlier discharge to home . The aim of the present study was to identify the differences in treatment between the SU and the GW and to assess which aspects of the SU care which were most responsible for the better outcome . METHODS Of the 220 patients included in our trial , only 206 were actually treated ( SU , 102 patients ; GW , 104 patients ) . For these patients , we identified the differences in the treatment and the consequences of the treatment . We analyzed the factors that we were able to measure and their association with the outcome , discharge to home within 6 weeks . RESULTS Characteristic features in our SU were teamwork , staff education , functional training , and integrated physiotherapy and nursing . Other treatment factors significantly different in the SU from the GW were shorter time to start of the systematic mobilization/training and increased use of oxygen , heparin , intravenous saline solutions , and antipyretics . Consequences of the treatment seem to be less variation in diastolic and systolic blood pressure ( BP ) , avoiding the lowest diastolic BP , and lowering the levels of glucose and temperature in the SU group compared with the GW group . Univariate analyses showed that all these factors except the level of glucose were significantly associated with discharge to home within 6 weeks . In the final multivariate Cox regression model , shorter time to start of the mobilization/training and stabilized diastolic BP were independent factors significantly associated with discharge to home within 6 weeks . CONCLUSIONS Shorter time to start of mobilization/training was the most important factor associated with discharge to home , followed by stabilized diastolic BP , indicating that these factors probably were important in the SU treatment . The effects of characteristic features of an SU , such as a specially trained staff , teamwork , and involvement of relatives , were not possible to measure . Such factors might be more important than those actually measured The aim of this prospect i ve , r and omized and controlled trial was to carry out and evaluate a model for follow-up by home visits after discharge from hospital of persons aged 75 years or more . The trial was a feasibility study in which hospital staff , district nurses , and general practitioners already working within the hospital and the primary health sector participated , with changes in the usual organization . On the day after their discharge from hospital , 163 patients were visited in their homes by the district nurse . Two weeks later , they were evaluated at home by their general practitioner . For 181 control patients , discharge took place according to the usual procedures . Endpoints were evaluated one year after discharge . Significantly more patients from the control group had been admitted to nursing homes as compared with the trial group ( 25/10 , p < 0.05 ) ; the control patients stayed 2700 days at institutions , the trial group 1950 days . It is proposed that this simple and practicable follow-up routine be introduced in connection with discharge of elderly persons from hospital BACKGROUND AND PURPOSE In an inner-London teaching hospital , a r and omized trial of " conventional " care versus early discharge to community-based therapy found no significant differences in clinical outcomes between patient groups . This report examines the economic consequences of the alternative strategies . METHODS One hundred sixty-seven patients received the early discharge package , and 164 received conventional care . Patient utilization of health and social services was recorded over a 12-month period , and cost was determined using data from provider departments and other published sources . RESULTS Inpatient stay after r and omization was 12 days ( intervention group ) versus 18 days ( controls ) ( P=0.0001 ) . Average units of therapy per patient were as follows : physiotherapy , 22.4 ( early discharge ) versus 15.0 ( conventional ) ( P=0.0006 ) ; occupational therapy , 29.0 versus 23.8 ( P=0.002 ) ; speech therapy , 13 . 7 versus 5.8 ( P=0.0001 ) . The early discharge group had more annual hospital physician contacts ( P=0.015 ) and general practitioner clinic visits ( P=0.019 ) but fewer incidences of day hospital attendance ( P=0.04 ) . Other differences in utilization were nonsignificant . Average annual costs per patient were pound sterling 6800 ( early discharge ) and pound sterling 7432 ( conventional ) . The early discharge group had lower inpatient costs per patient ( pound sterling 4862 [ 71 % of total cost ] versus pound sterling 6343 [ 85 % ] for controls ) but higher non-inpatient costs ( pound sterling 1938 [ 29 % ] versus pound sterling 1089 [ 15 % ] ) . Further analysis demonstrated that early discharge is unlikely to lead to financial savings ; its main benefit is to release capacity for an expansion in stroke caseload . CONCLUSIONS Overall results of this trial indicate that early discharge to community rehabilitation for stroke is cost-effective . It may provide a means of addressing the predicted increase in need for stroke care within existing hospital capacity CONTEXT Although home-based health care has grown over the past decade , its effectiveness remains controversial . A prior trial of Veterans Affairs ( VA ) Team-Managed Home-Based Primary Care ( TM/HBPC ) found favorable outcomes , but the replicability of the model and generalizability of the findings are unknown . OBJECTIVES To assess the impact of TM/HBPC on functional status , health-related quality of life ( HR-QoL ) , satisfaction with care , and cost of care . DESIGN AND SETTING Multisite r and omized controlled trial conducted from October 1994 to September 1998 in 16 VA medical centers with HBPC programs . PARTICIPANTS A total of 1966 patients with a mean age of 70 years who had 2 or more activities of daily living impairments or a terminal illness , congestive heart failure ( CHF ) , or chronic obstructive pulmonary disease ( COPD ) . Intervention Home-based primary care ( n=981 ) , including a primary care manager , 24-hour contact for patients , prior approval of hospital readmissions , and HBPC team participation in discharge planning , vs customary VA and private sector care ( n=985 ) . MAIN OUTCOME MEASURES Patient functional status , patient and caregiver HR-QoL and satisfaction , caregiver burden , hospital readmissions , and costs over 12 months . RESULTS Functional status as assessed by the Barthel Index did not differ for terminal ( P=.40 ) or nonterminal ( those with severe disability or who had CHF or COPD ) ( P=.17 ) patients by treatment group . Significant improvements were seen in terminal TM/HBPC patients in HR-QoL scales of emotional role function , social function , bodily pain , mental health , vitality , and general health . Team-Managed HBPC nonterminal patients had significant increases of 5 to 10 points in 5 of 6 satisfaction with care scales . The caregivers of terminal patients in the TM/HBPC group improved significantly in HR-QoL measures except for vitality and general health . Caregivers of nonterminal patients improved significantly in QoL measures and reported reduced caregiver burden ( P=.008 ) . Team-Managed HBPC patients with severe disability experienced a 22 % relative decrease ( 0.7 readmissions/patient for TM/HBPC group vs 0.9 readmissions/patient for control group ) in hospital readmissions ( P=.03 ) at 6 months that was not sustained at 12 months . Total mean per person costs were 6.8 % higher in the TM/HBPC group at 6 months ( $ 19190 vs $ 17971 ) and 12.1 % higher at 12 months ( $ 31401 vs $ 28008 ) . CONCLUSIONS The TM/HBPC intervention improved most HR-QoL measures among terminally ill patients and satisfaction among non-terminally ill patients . It improved caregiver HR-QoL , satisfaction with care , and caregiver burden and reduced hospital readmissions at 6 months , but it did not substitute for other forms of care . The higher costs of TM/HBPC should be weighed against these benefits Abstract Objectives : To compare the costs of admission to a hospital at home scheme with those of acute hospital admission . Design : Cost minimisation analysis within a pragmatic r and omised controlled trial . Setting : Hospital at home scheme in Leicester and the city 's three acute hospitals . Participants : 199 consecutive patients assessed as being suitable for admission to hospital at home for acute care during the 18 month trial period ( median age 84 years ) . Intervention : Hospital at home or hospital inpatient care . Main outcome measures : Costs to NHS , social services , patients , and families during the initial episode of treatment and the three months after admission . Results : Mean ( median ) costs per episode ( including any transfer from hospital at home to hospital ) were similar when analysed by intention to treat — hospital at home £ 2569 ( £ 1655 ) , hospital ward £ 2881 ( £ 2031 ) , bootstrap mean difference −305 ( 95 % confidence interval −1112 to 448 ) . When analysis was restricted to those who accepted their allocated place of care , hospital at home was significantly cheaper — hospital at home £ 2557 ( £ 1710 ) , hospital ward £ 3660 ( £ 2903 ) , bootstrap mean difference −1071 ( −1843 to −246 ) . At three months the cost differences were sustained . Costs with all cases included were hospital at home £ 3671 ( £ 2491 ) , hospital ward £ 3877 ( £ 3405 ) , bootstrap mean difference −210 ( −1025 to 635 ) . When only those accepting allocated care were included the costs were hospital at home £ 3698 ( £ 2493 ) , hospital ward £ 4761 ( £ 3940 ) , bootstrap mean difference −1063 ( −2044 to −163 ) ; P=0.009 . About 25 % of the costs for episodes of hospital at home were incurred through transfer to hospital . Costs per day of care were higher in the hospital at home arm ( mean £ 207 v £ 134 in the hospital arm , excluding refusers , P<0.001 ) . Conclusions : Hospital at home can deliver care at similar or lower cost than an equivalent admission to an acute hospital We previously conducted a r and omized controlled trial in which early supported discharge from the Department of Neurology at Huddinge Hospital in southwest Stockholm with continuity of rehabilitation at home ( n = 41 ) was compared to routine rehabilitation services ( n = 40 ) for moderately disabled selected stroke patients . No statistical significant differences were found in patient outcome at 3 or 6 months , but a moderately positive effect in the home rehabilitation group was suggested . In the present study we evaluated re source utilization of health and social care , impact on family caregivers during 6 months after acute stroke and patient satisfaction . A 50 % reduction in total hospitalization ( initial and recurrent ) was observed , from 30 days in the routine rehabilitation group to 15 days in the home rehabilitation group ( p < 0.001 ) . After discharge , the mean number of home visits in the home rehabilitation group was 12 . In total , the routine rehabilitation group had a higher frequency of therapy contacts and daycare in outpatient care . Seventy-eight percent received help from a family caregiver in activities of daily living , yet only 15 % had formal home help service . No major differences were found in use of home help service or impact on family caregivers in the form of time devoted to helping the patient or subjective well-being of spouses as per Sickness Impact Profile . Patient satisfaction was in favour of the home rehabilitation group , but a significant difference was only found in active participation in rehabilitation programme planning . In conclusion , early supported discharge with continuity of rehabilitation at home , using goal -directed functional activities based on the patient 's personal interests , should be the rehabilitation service of choice for moderately disabled stroke patients fulfilling certain criteria , provided that further evaluation during the first year after stroke reveals no great changes in outcome or re source use . More research into the effectiveness and cost implication s of early supported discharge with continuity of rehabilitation at home is needed in other parts of Sweden and in other countries before it can be asserted that the conclusions drawn from this study are applicable elsewhere Hospital-at-Home schemes have been cl aim ed to hasten the discharge of elderly orthopaedic patients , and are becoming increasingly popular with health service managers . In an attempt to measure the benefits of such a scheme when applied to elderly medical patients , we prospect ively r and omized 60 consecutive referrals of patients approaching discharge either to the Hospital-at-Home ( HAH ) rehabilitation team , or to conventional discharge ( CD ) preparation and domiciliary support . Patients allocated to HAH were discharged on average 5 days earlier than CD , while 64 % of each group remained at home during 6 months follow-up . Improvements in independence were modest , and similar in the two groups , though a trend favoured HAH Abstract Objectives : To compare “ hospital at home ” and hospital care as an inpatient in acute exacerbations of chronic obstructive pulmonary disease . Design : Prospect i ve r and omised controlled trial with three months ' follow up . Setting : University teaching hospital offering secondary care service to 350 000 patients . Patients : Selected patients with an exacerbation of chronic obstructive pulmonary disease where hospital admission had been recommended after medical assessment . Interventions : Nurse administered home care was provided as an alternative to inpatient admission . Main outcome measures : Readmission rates at two weeks and three months , changes in forced expiratory volume in one second ( FEV1 ) from baseline at these times and mortality . Results : 583 patients with chronic obstructive pulmonary disease referred for admission were assessed . 192 met the criteria for home care , and 42 refused to enter the trial . 100 were r and omised to home care and 50 to hospital care . On admission , FEV1 after use of a bronchodilator was 36.1 % ( 95 % confidence interval 2.4 % to 69.8 % ) predicted in home care and 35.1 % ( 6.3 % to 63.9 % ) predicted in hospital care . No significant difference was found in FEV1 after use of a bronchodilator at two weeks ( 42.6 % , 3.4 % to 81.8 % versus 42.1 % , 5.1 % to 79.1 % ) or three months ( 41.5 % , 8.2 % to 74.8 % versus 41.9 % , 6.2 % to 77.6 % ) between the groups . 37 % of patients receiving home care and 34 % receiving hospital care were readmitted at three months . No significant difference was found in mortality between the groups at three months ( 9 % versus 8 % ) . Conclusions : Hospital at home care is a practical alternative to emergency admission in selected patients with exacerbations of chronic obstructive pulmonary disease Home and hospital management of patients with suspected myocardial infa rct ion were compared in a r and omised trial in which a hospital-based team responded to calls from general practitioners . 500 calls were received , and 349 patients ( 70 % ) were suspected of having myocardial infa rct ion . Of these , 24 % were excluded from the trial on predetermined medical and social grounds ; for the remainder ( 76 % ) there was no significant difference in the 6-week mortality between the home group ( 13 % ) and the hospital group ( 11 % ) . For the majority of patients to whom a general practitioner is called because of suspected infa rct ion , hospital admission confers no clear advantage A r and omized controlled trial was conducted to evaluate the efficacy of the early transfer of hospital in- patients to home care . This paper reports rates of return to normal role functions in work , leisure and household roles for patients who received any of five surgical procedures . With regard to return to work or leisure tasks , no statistically significant differences were observed between groups for any of the procedures . The rates of return to household activities were greater for home care patients than they were for controls in the cases of cholecystectomy and procedures for anal and rectal fistula A 6-month follow-up of a single-blind , r and omized , controlled trial in Southwest Stockholm was performed in order to evaluate the effect of early supported discharge and continued rehabilitation at home after stroke . Eighty-three stroke patients with moderate neurological impairments , continent , independent in feeding , and mental function within normal limits one week after onset were included in the study . The patients were allocated 1:1 to early supported discharge and continued rehabilitation at home by a specialized team , versus routine rehabilitation . Patient outcomes measured were motor capacity , dysphasia , activities of daily living , social activities , perceived dysfunction , mortality and reported falls . Data on length of stay in hospital ; initial and recurrent during 6 months were compared . The 6-month follow-up of 78 patients showed no statistically significant differences in patient outcome . The results of multivariate logistic regression analysis suggest a positive effect of home rehabilitation on activities of daily living . At 3 - 6 months the frequency of significant improvements was higher in the intervention group . Death or dependency in activities of daily living was 24 % in the intervention group compared with 44 % in the control group . The mean initial hospitalization was 29 days in routine rehabilitation group versus 14 days in the home rehabilitation group . We conclude that for moderately disabled stroke patients with mental function within normal limits , early supported discharge and continued rehabilitation at home had no less a beneficial effect on patient outcome than routine rehabilitation , reduced initial hospitalization significantly and had no adverse effects on mortality and number of falls This trial compared the cost of an integrated home-based care model with traditional inpatient care for acute chronic obstructive pulmonary disease ( COPD ) . 25 patients with acute COPD were r and omised to either home or hospital management following request for hospital admission . The acute care at home group costs per separation ( $ 745 , CI95 % $ 595-$895 , n = 13 ) were significantly lower ( p < 0.01 ) than the hospital group ( $ 2543 , CI95 % $ 1766-$3321 , n = 12 ) . There was an improvement in lung function in the hospital-managed group at the Outpatient Department review , decreased anxiety in the Emergency Department in the home-managed group and equal patient satisfaction with care delivery . Acute care at home schemes can substitute for usual hospital care for some patients without adverse effects , and potentially release re sources . A funding model that allows adequate re source delivery to the community will be needed if there is a move to devolve acute care to community providers This report describes the findings of a r and omized study of a new team approach to home care for homebound chronically or terminally ill elderly . The team includes a physician , nurse practitioner , and social worker delivering primary health care in the patient 's home , including physician house calls . Weekly team conferences assure coordination of patient care . The team is available for emergency consultation through a 24-hour telephone service . The team physician attends to the patient during necessary hospitalizations . This approach was evaluated in a r and omized experimental design study measuring its impact on health care utilization , functional changes in patients , and patient and caretaker satisfaction . The team patients had fewer hospitalizations , nursing home admissions , and outpatient visits than the controls . They were more often able to die at home , if this was their wish . As expected , they used more in-home services , measured in weighted cost figures ; their overall cost was lower than their controls , but the difference was not statistically significant . Their functional abilities did not change differently from the controls , but they , and especially their informal caretakers in the home , expressed significantly higher satisfaction with the care received Objective : To establish the feasibility and method of evaluation of an early supported hospital discharge policy for patients with acute stroke . Design : A r and omized controlled trial comparing an early supported discharge service to conventional care . Setting : Three acute hospitals in Newcastle upon Tyne . Subjects : Ninety-two eligible patients with acute stroke admitted between 1 February 1995 and 31 January 1996 . Main outcome measures : Placement , length of stay , readmission rates , mortality , functional ability ( Nottingham Extended Activities of Daily Living ( ADL ) Scale ) , h and icap ( Oxford H and icap Scale ) , global health status ( Dartmouth Coop Function Charts ) and carer stress ( General Health Question naire 30 item ) . Results : The median length of stay for patients r and omized to early supported discharge was 13 days compared to 22 days in the conventional care group ( p = 0.02 ) . The median Barthel ADL Index at seven days post stroke of patients r and omized to early supported discharge was 15 , and 13 for those r and omized to conventional care ( NS ) . At three months post stroke the median Nottingham EADL score of patients r and omized to early supported discharge was 10 compared to 7 for those who received conventional care ( NS ) . There were no statistically significant differences in the global health status of patients or carer stress . Conclusion : An early supported discharge service following acute stroke with individualized rehabilitation in the community is feasible and can be evaluated by a r and omized controlled trial but a larger multicentre trial is needed before such a service is widely adopted Abstract Objective : To compare effectiveness and acceptability of early discharge to a hospital at home scheme with that of routine discharge from acute hospital . Design : Pragmatic r and omised controlled trial . Setting : Acute hospital wards and community in north of Bristol , with a catchment population of about 224 000 people . Subjects : 241 hospitalised but medically stable elderly patients who fulfilled criteria for early discharge to hospital at home scheme and who consented to participate . Interventions : Patients ' received hospital at home care or routine hospital care . Main outcome measures : Patients ' quality of life , satisfaction , and physical functioning assessed at 4 weeks and 3 months after r and omisation to treatment ; length of stay in hospital and in hospital at home scheme after r and omisation ; mortality at 3 months . Results : There were no significant differences in patient mortality , quality of life , and physical functioning between the two arms of the trial at 4 weeks or 3 months . Only one of 11 measures of patient satisfaction was significantly different : hospital at home patients perceived higher levels of involvement in decisions . Length of stay for those receiving routine hospital care was 62 % ( 95 % confidence interval 51 % to 75 % ) of length of stay in hospital at home scheme . Conclusions : The early discharge hospital at home scheme was similar to routine hospital discharge in terms of effectiveness and acceptability . Increased length of stay associated with the scheme must be interpreted with caution because of different organisational characteristics of the services . Key messages Pressure on hospital beds , the increasing age of the population , and high costs associated with acute hospital care have fuelled the search for alternatives to inpatient hospital care There were no significant differences between early discharge to hospital at home scheme and routine hospital care in terms of patient quality of life , physical functioning , and most measures of patient satisfaction Length of stay for hospital patients was significantly shorter than that of hospital at home patients , but , owing to qualitative differences between the two interventions , this does not necessarily mean differences in effectiveness Early discharge to hospital at home provides an acceptable alternative to routine hospital care in terms of effectiveness and patient Objective : To compare hospital and home setting s for the rehabilitation of patients following hip fracture . Design : R and omized controlled trial comparing accelerated discharge and home-based rehabilitation ( n = 34 ) with conventional hospital care ( n = 32 ) for patients admitted to hospital with hip fracture . Setting : Three metropolitan hospitals in Adelaide , Australia . Subjects : Sixty-six patients with fractured hip . Interventions : Patients assigned to the home-based rehabilitation group were discharged within 48 hours of r and omization . The project team therapists made visits to the patient ’s home and negotiated a set of realistic , short-term and measurable treatment goals with both the patient and carer . Those r and omized to usual care remained in hospital for conventional rehabilitation . Main outcome measures : Physical and social dependence , balance con”dence , quality of life , carer strain , patient and carer satisfaction , use of community services and incidence of adverse events such as re-admission and falls . Results : While there was no difference between the groups for all measures of quality of life , patients in the accelerated discharge and home-based rehabilitation group recorded a greater improvement in MBI from r and omization ( p < 0.05 ) and scored higher on the Falls Ef”cacy Scale ( p < 0.05 ) at four months . There was no difference in falls rates . Patients in the home-based rehabilitation group had a shorter stay in hospital ( p < 0.05 ) but a longer stay in rehabilitation overall ( p < 0.001 ) . The groups were comparable on the rate and length of admissions after discharge , use of community services , need for carer input and contact with general practitioner ( GP ) after discharge Abstract Objective : To evaluate the impact on place of death of a hospital at home service for palliative care . Design : Pragmatic r and omised controlled trial . Setting : Former Cambridge health district . Participants : 229 patients referred to the hospital at home service ; 43 r and omised to control group ( st and ard care ) , 186 r and omised to hospital at home . Intervention : Hospital at home versus st and ard care . Main outcome measures : Place of death . Results : Twenty five ( 58 % ) control patients died at home compared with 124 ( 67 % ) patients allocated to hospital at home . This difference was not significant ; intention to treat analysis did not show that hospital at home increased the number of deathsat home . Seventy three patients r and omised to hospital at home were not admitted to the service . Patients admitted to hospital at home were significantly more likely to die at home ( 88/113 ; 78 % ) than control patients . It is not possible to determine whether this was due to hospital at home itself or other characteristics of the patients admitted to the service . The study attained less statistical power than initially planned . Conclusion : In a locality with good provision of st and ard community carewe could not show that hospital at home allowed more patients to die at home , although neither does the study refute this . Problems relating to recruitment , attrition , and the vulnerability of the patient group make r and omised controlled trials in palliative care difficult . Whilethese difficulties have to be recognised they are not insurmountable with the appropriateresourcing and setting . Key messages Terminally ill patients allocated to hospital at home were no more likely to die at home than patients receiving st and ard care Although the sub sample of patients actually admitted to hospital at home did show a significant increase in likelihood of dying at home , whether this was due to theservice itself or the characteristics of patients admitted to hospital at home could not be determined The need to balance ideal research design against the realities of evaluation of palliative care had the effect that the trial achieved less statistical power than originally planned Particular problems were that many patients failed to receive the allocatedintervention because of the unpredictable nature of terminal illness , inclusion of other service input alongside hospital at home , and the wide range of st and ard care available The trial illustrated problems associated with r and omised controlled trialsin palliative care , none of which are insurmountable but which require careful consideration and resourcing before future trials are The community health services in Southern Derbyshire , in conjunction with an acute hospital , established a pilot scheme for the early discharge of fractured neck of femur patients from hospital to their own homes . The scheme was evaluated by prospect ively comparing a group of patients using Hospital at Home ( HAH ) and a group receiving hospital care only . The main outcomes measured were the proportion of hospital admissions for fractured neck of femur using HAH , length of stay , patient satisfaction , general health status at discharge as measured by the Nottingham Health Profile , and three-month mortality and readmission rates . Costs were calculated based on prices charged by providers of the services . In the first year of the scheme , 76 ( 18 per cent ) of the 432 hospital admissions for fractured neck of femur fitted the selection criteria and agreed to admission to HAH . Thirty-four patients were identified who were suitable for HAH but not admitted to it . The comparison of the 76 HAH patients and 34 hospital patients revealed that HAH patients were discharged from hospital an average of 7 days earlier ; patients in both groups were satisfied with the care they received ; the general health status of the two groups at discharge was similar , with the exception that HAH patients had better emotional health on discharge from care ; the three-month mortality rate was similar in both groups ( 5 per cent ) ; the readmission rate for HAH patients appeared higher than for hospital patients but this difference was not statistically significant ( 15.8 per cent versus 8.8 per cent , Fisher 's exact test , p = 0.187 ) . ( ABSTRACT TRUNCATED AT 250 WORDS OBJECTIVES To evaluate whether home treatment of elderly patients with acute uncomplicated first ischemic stroke is associated with different mortality rates and clinical outcomes from those of patients treated on a general medical ward ( GMW ) . DESIGN R and omized , controlled , single-blind trial . SETTING S. Giovanni Battista Hospital of Turin . PARTICIPANTS One hundred twenty elderly patients admitted to the emergency department of the hospital with first acute ischemic stroke were r and omized to home treatment from a geriatric home hospitalization service ( GHHS ) or to GMW treatment . MEASUREMENT Main outcome was cumulative survival at 6 months in the two groups . Residual functional impairment , neurological deficit , depression , morbidity , and admission to rehabilitation and long-term care facilities were considered as secondary outcomes in survivors . RESULTS One hundred twenty patients ( mean age 82 ; 54 men and 66 women ) were enrolled ( 60 in each study arm ) . The cumulative proportion of cases surviving at 6 months was 0.65 in the GHHS group and 0.60 in GMW group ( log-rank test P=.53 ) . Functional and neurological parameters were significantly improved in both GHHS and GMW patients , without significant differences between the two groups . Depression score was significantly better in home-treated patients ( P<.001 ) , who were more likely to remain at home at 6 months than hospital-treated patients and had a lower rate of select medical complications . CONCLUSION Home-treated elderly patients with ischemic stroke have better depressive scores and lower rates of admission to nursing homes . These results should prompt further studies to evaluate home hospitalization for elderly stroke patients Abstract Objective : To assess the clinical effectiveness of an early discharge policy for patients with stroke by using a community based rehabilitation team . Design : R and omised controlled trial to compare conventional care with an early discharge policy . Setting : Two teaching hospitals in inner London . Subjects : 331 medically stable patients with stroke ( mean age 71 ) who lived alone and were able to transfer independently or who lived with a resident carer and were able to transfer with help . Interventions : 167 patients received specialist community rehabilitation for up to 3 months after r and omisation . 164 patients continued with conventional hospital and community care . Main outcome measures : Barthel score at 12 months . Secondary outcomes measured impairment with motoricity index , minimental state examination , and Frenchay aphasia screening test ; disability with the Rivermead activity of daily living scales , hospital anxiety and depression scale , and 5 m walk ; h and icap with the Nottingham health profile ; carer stress with caregiver strain index and patient and carer satisfaction . The main process measure was length of stay after r and omisation . Results : One year after r and omisation no significant differences in clinical outcomes were found apart from increased satisfaction with hospital care in the community therapy group . Length of stay after r and omisation in the community therapy group was significantly reduced ( 12 v 18 days ; P<0.0001 ) . Patients with impairments were more likely to receive treatment in the community therapy group . Conclusions : Early discharge with specialist community rehabilitation after stroke is feasible , as clinical ly effective as conventional care , and acceptable to patients . Considerable reductions in use of hospital beds are achievable . Key messages Early discharge from hospital after stroke with specialist rehabilitation at home is feasible without an increase in readmission rates or stress to carers This r and omised controlled trial shows this method to be as effective as conventional care when assessed with a range of measures of impairment , disability , h and icap , carer stress , and patient and carer satisfaction at 1 year Significant reductions in bed usage can be achieved by the provision of a community rehabilitation team with no significant increase in rehabilitation The aim of this study was to determine the effect of the reduction of the length of hospital stay after surgery for breast cancer on the rate of care consumption and the cost of care . Patients with operable breast cancer were r and omised to a short or long postoperative hospital stay . Data on care consumption were collected for a period of 4 months in diaries administered by patients , and socioeconomic status was evaluated by question naires . A cost minimisation analysis using the ' societal ' perspective was performed and savings were compared with the savings of hospital charges . The use of professional home care was higher for the short stay group during the first month ( 7.2 versus 1.3 h , P < 0.0001 ) . The number of out-patient consultations , the intensity of informal home care and patient 's expenses did not increase after early discharge . The total cost of care was reduced by US$ 1320 by introducing the short stay programme ( P = 0.0007 ) , but the savings were substantially lower than the savings in hospital charges ( US$ 2680 ) BACKGROUND The Palliative Medicine Unit at University Hospital of Trondheim , Norway , started an intervention programme that aims to enable patients to spend more time at home and die there if they prefer . Close cooperation was needed with the community health-care professionals , who acted as the principal formal caregivers , and a multidisciplinary consultant team coordinated the care . We did a cluster r and omised trial to assess the intervention 's effectiveness compared with conventional care METHODS Community health-care districts in and around Trondheim , Norway , were defined as the clusters to be r and omised . We enrolled 434 patients ( 235 assigned intervention and 199 conventional care [ controls ] ) in these districts who had incurable malignant disease and an expected survival of 2 - 9 months . Main outcomes were place of death and time spent in institutions in the last month of life . FINDINGS 395 patients died . Of these , more intervention patients than controls died at home ( 54 [ 25 % ] vs 26 [ 15 % ] , p<0.05 ) . The time spent at home was not significantly increased , although intervention patients spent a smaller proportion of time in nursing homes in the last month of life than did controls ( 7.2 vs 14.6 % , p<0.05 ) . Hospital use was similar in the two groups . INTERPRETATION The palliative-care intervention enabled more patients to die at home . More re sources for care in the home ( palliative care training and staff ) and an increased focus on use of nursing homes would be necessary , however , to increase time at home and reduce hospital admissions Background : Patients with an acute exacerbation of chronic obstructive pulmonary disease ( COPD ) were r and omised to either hospital at home ( HaH ) or inpatient management , and patient and carer preferred site of management and satisfaction with care received in the two arms was determined . Methods : Emergency admissions with an acute exacerbation of COPD were r and omised to inpatient care or HaH care . After discharge an independent observer administered a question naire to both patients and carers on the preferred site of care and scored satisfaction with the care received . Results : Of 60 patients recruited , 30 were r and omised to receive HaH care . Retrospective patient preference for HaH care was 96.3 % in the domiciliary arm and 59.3 % in the conventional arm ; carer preference figures were 85.7 % and 42.9 % , respectively . There was a higher preference for domiciliary care by both patients and carers in the HaH arm than in the inpatient arm ( p=0.001 and p=0.01 , respectively ) . Patients recorded equal satisfaction with care in the two arms ( 88.1 % in the conventional arm , 91.7 % in the domiciliary arm ) ; carer scores were 91.3 % and 91.9 % , respectively . Conclusions : The results of this study show that both patients and carers were significantly more likely to prefer domiciliary care if they were in the HaH arm . Since patients had to be willing to be looked after at home , both patients ' and carers ' perceptions of the benefits of HaH care were reinforced by their experience . HaH care of acute exacerbations of COPD is the preferred option in suitable patients This study evaluated the impact of a Cambridge hospital at home service ( CHAH ) on patients ' quality of care , likelihood of remaining at home in their final 2 weeks of life and general practitioner ( GP ) visits . The design was a r and omized controlled trial , comparing CHAH with st and ard care . The patient 's district nurse , GP and informal carer were surveyed within 6 weeks of patient 's death , and 225 district nurses , 194 GPs and 144 informal carers of 229 patients responded . There was no clear evidence that CHAH increased likelihood of remaining at home during the final 2 weeks of life . However , the service was associated with fewer GP out of hours visits . All respondent groups rated CHAH favourably compared to st and ard care but emphasized different aspects . District nurses rated CHAH as better than st and ard care in terms of adequacy of night care and support for the carer , GPs in terms of anxiety and depression , and informal carers in terms of control of pain and nausea . Thus whilst CHAH was not found to increase the likelihood of remaining at home , it appeared to be associated with better quality home care The purpose of this study was to evaluate the impact of a primary home care intervention program on patient outcomes after selected patients were discharged from a short-stay hospital . R and om assignment of 249 frail , elderly patients was made to a group provided with physician-led primary home care , and home assistance service on a 24-hour basis , or to a control group given st and ard care . At r and omization , patients were considerably disabled , had a mean age of 80.5 years , and had a high likelihood of long-stay hospital care . Medical and functional data were essentially the same at baseline for both groups . At 6-months follow-up , significant improvement in instrumental activities of daily living ( P = 0.04 ) and outdoor walking ( P = 0.03 ) , and medical condition was found in the primary care intervention group compared with the controls and less utilization of long-stay hospital facilities was displayed in the team patients ( P < 0.001 ) than in the controls . A selection of elderly , dependent patients can be cared for in their homes after short-stay hospital discharge and benefit from this primary home care intervention program in terms of improved medical and functional outcomes and less long-stay hospitalization Inconsistent results in studies of cost-effectiveness of home health care have led to the need for identification of target population s for whom cost-savings can be anticipated if exp and ed home care programs are introduced . This analysis of results of a r and omized controlled study of efficacy of a physician/geriatric nurse practitioner/social worker home care team identifies such a potential target population . The team provides round-the-clock on-call medical services in the home when needed , in addition to usual nursing and other home care services , to home-bound chronically or terminally ill elderly patients . Overall health services utilization and estimated costs were not substantially different for the patients who did not die while in the study ; however , for those who did die , team patients had considerably lower rates of hospitalization and overall cost than controls , and more frequently died at home . Of 21 team and 12 control patients who died but had at least two weeks of utilization experience in the study , team patients had about half the number of hospital days compared with controls during the terminal two weeks , and although they had more home care services , had only 69 per cent of the estimated total health care costs of the controls . Satisfaction with care received was significantly greater among the total group of team patients , and especially among their family caretakers , than among controls . This model is effective in providing appropriate medical care for seriously ill and terminal patients , and in enabling them to die at home if they so wish , while at the same time reducing costs of care during the terminal period In a study comparing two regimens of treatment after intra-articular irradiation of the knee with yttrium-90 one group of patients was allocated to bed rest for 48 hours in hospital and the other to mobilisation at home . Initially a Robert-Jones orthopaedic b and age was applied to the knee in all patients , serving as a semi-rigid splint , but as loss of isotope from the knee was appreciable in the mobilised patients , subsequent patients were sent home with the knee in a plaster-of-Paris cylinder . No difference in extra-articular spread or chromosomal damage was found between the patients sent home with their knee in a rigid splint and those treated by bed rest . Clinical outcome at three months was satisfactory in all three groups . These results show that rigid splinting is essential in reducing extra-articular spread of the isotope but that bed rest is not necessary . Increases in intra-articular pressure associated with quadriceps muscle activity combined with flexion of the knee may be the most important factor affecting extra-articular spread of isotope Abstract Objective : To compare , from the viewpoints of the NHS and social services and of patients , the costs associated with early discharge to a hospital at home scheme and those associated with continued care in an acute hospital . Design : Cost minimisation analysis . Setting : Acute hospital wards and the community in the north of Bristol ( population about 224 000 ) . Subjects : 241 hospitalised but medically stable elderly patients who fulfilled the criteria for early discharge to a hospital at home scheme and who consented to participate . Main outcome measures : Costs to the NHS , social services , and patients over the 3 months after r and omisation . Results : The mean cost for hospital at home patients over the 3 months was £ 2516 , whereas that for hospital patients was £ 3292 . Under all the assumptions used in the sensitivity analysis , the cost of hospital at home care was less than that of hospital care . Only when hospital costs were assumed to be less than 50 % of those used in the initial analysis was the difference equivocal . Conclusions : The hospital at home scheme is less costly than care in the acute hospital . These results may be generalisable to schemes of similar size and scope , operating in a similar context of rising acute admissions . Key messages Some economic evaluations have found that hospital at home care is more costly than acute hospital care in the United Kingdom , and others have found that it is less costly Cost minimisation analysis found a mean cost to the NHS and social services of £ 2516 per hospital at home patient and £ 3292 per hospital patient For every £ 10 000 spent , routine hospital care could be provided for three patients , while early discharge to care in the hospital at home scheme could be provided for four patients Sensitivity analysis ( making differing assumptions for the cost of both services within reasonable boundaries ) does not change the result that hospital at home is less costly than hospital care ; only when hospital costs are assumed to be less than 50 % of the original estimate does the difference become equivocal Costs to patients were similar in the two arms of the The rehabilitation of elderly patients after hip fractures is important : we report a prospect i ve study which compares supported home rehabilitation with management in hospital in two similar groups of patients . Our results show that early discharge from hospital and home rehabilitation produces substantial savings in bed days , and also provides quicker and more effective recovery In a controlled trial of a home-care service available for the first 6 months after acute stroke , 440 patients received the new service and 417 patients were in the control group . The trial group used more hospital bed days , had a slightly higher admission rate , and did not show better emotional adjustment to stroke than the control group . There was no difference between the 2 groups in stress on relatives . Functional recovery was equal in the 2 groups . A quarter of patients managed at home in each group were severely disabled . Providing a new service does not necessarily alter clinical decisions in the short term , and care should be taken before exp and ing domiciliary services to reduce hospital use Alternative systems of care after operations for varicose veins or hernia were compared in a total of 360 selected patients , of whom 121 were allocated to be managed in an acute ward for 48 h , 122 in a convalescent hospital for 48 h and 117 to be discharged directly home to the care of the district nursing sister and general practitioner . There were no deaths or major complications . Anaesthetic or surgical problems caused 5 patients ( 3 convalescent and 2 day care ) to be retained in hospital on the day of operation . Minor complications were recorded in approximately one‐third of the patients . The majority of these were effectively dealt with by the district nursing sister and only one‐third of the complications needed the attention of the general practitioner . Two of the ward patients and 1 of the convalescent patients required readmission to hospital ( 1 per cent in all ) . No significant difference was demonstrated in the medical outcome between the three groups after operation . Day care was the most economical of the three systems of care . Inquiry into the patients ' opinions elicited the highest proportion of favourable responses in the day care group The Home Treatment Team ( HTT ) , a hospital discharge team for elderly patients , was created to provide practical help and promote independence of patients at home for up to 6 weeks after hospital discharge . Patients were those judged to be at particular risk of failing to resettle , and thus being readmitted to hospital or admitted to a residential or nursing home . An open r and omized controlled trial compared patients receiving the HTT ( n = 29 ) with controls ( n = 25 ) receiving appropriate conventional community services . Fewer HTT patients were readmitted ( four by 6 weeks and nine by 12 weeks ) than controls ( nine by 6 weeks and 14 by 12 weeks , p < 0.05 ) and more were at home at 6 weeks ( 24 , 83 % and 10 , 40 % , p < 0.05 ) , 12 weeks ( 21 , 72 % and 11 , 44 % , p < 0.05 ) and 12 months ( 17 , 58 % and 10 , 40 % , p < 0.05 ) . The HTT group spent fewer days in hospital than controls during 12 weeks ( median difference 34 days , 95 % confidence interval 0 - 75 , p < 0.05 ) and more days at home during 12 months ( 90 ; 247 - 0 , p = 0.02 ) . Neither group showed any significant change in mental state or functional abilities over 12 weeks . Potentially confounding factors were considered insufficient explanation for the difference in outcome between the groups . It is concluded that the HTT was of benefit but the mechanism of its effect was not identified Abstract Objective : To determine the effect of early discharge from hospital after surgery for breast cancer on physical and psychological illness . Design : R and omised controlled trial comparing discharge two days after surgery ( before removal of drain ) with st and ard management ( discharge after removal of drain ) . Setting : Regional breast unit . Subjects : 100 women with early breast cancer undergoing mastectomy and axillary node clearance ( 20 ) or breast conservation surgery ( 80 ) . Main outcome measures : Physical illness ( infection , seroma formation , shoulder movement ) and psychological illness ( checklist of concerns , Rotterdam symptom question naire , hospital anxiety and depression scale ) preoperatively and at one month and three months postoperatively . Results : Women discharged early had greater shoulder movement ( odds ratio 0.28 ( 95 % confidence interval 0.08 to 0.95 ) ; P=0.042 ) and less wound pain ( odds ratio 0.28 ( 0.10 to 0.79 ) ; P=0.016 ) three months after surgery compared with women given st and ard management . One month after surgery scores were significantly lower on the Rotterdam symptom question naire in patients who were discharged early ( ratio of geometric mean scores 0.73 ( 0.55 to 0.98 ) ; P=0.035 ) , but rates of psychological illness generally did not differ between groups . Conclusions : Increased rates of physical or psychological illness did not result from early discharge after surgery for breast cancer . This policy can be recommended for patients with support at home This study was design ed to test whether previously untreated patients with head and neck cancer could effectively manage home continuous infusion chemotherapy , and to compare their acceptance and adjustment to home versus inpatient treatment . Twenty-two patients received 3 - 4 cycles of induction chemotherapy and a 5-day continuous intravenous infusion ( CVI ) . Patients were r and omized to receive the CVI portion of cycle 1 either in the hospital via a st and ard chemotherapy delivery device or at home via the Travenol Infusor , a portable and disposable drug delivery system . For their second cycle of chemotherapy , patients crossed over to the alternate drug delivery method . Patients who did not want to receive their treatment at home received their chemotherapy as in patients via the Infusor . Therefore , all patients received treatment with both drug delivery methods . Nineteen patients were evaluable for this study . Eleven patients received at least one cycle of home CVI chemotherapy , and adjusted well to this method of drug delivery . Levels of psychological distress decreased for this group of patients when receiving outpatient chemotherapy compared to their inpatient cycles . The eight patients who received all chemotherapy cycles as in patients ( refused home treatment ) were found to be less educated and reported greater physical impairment prior to study entry than future home CVI acceptors . Levels of psychological distress in this group increased with each inpatient chemotherapy cycle . We conclude that home CVI chemotherapy may be an alternative to inpatient treatment for patients who have had at least one cycle of inpatient chemotherapy . The best c and i date s for home treatment are patients with unimpaired daily functioning and a minimum high school education OBJECTIVES To investigate whether care of elderly and disabled patients could be more cost-effective after a short-term hospital stay , we examined the impact of a primary home care intervention program on functional status , use and costs of care after 6 months . METHODS When clinical ly ready for discharge from the hospital , chronically ill patients with dependence in one to five functions in personal activities of daily living were r and omized to physician-led primary home care with a 24-hour service , and the controls were offered ordinary care . Physical , cognitive , social , and medical functions were assessed in 110 team subjects and 73 controls . Data regarding inpatient days and outpatient visits were collected and converted to costs . RESULTS Team patients demonstrated better instrumental activities of daily living and outdoor walking and significantly fewer diagnoses and drugs at 6 months . They used less inpatient and more outpatient care compared with the control patients . Significant cost reductions were found in the team group . CONCLUSIONS This primary home care intervention program is cost-effective , at least for a selection of patients at risk for long-term hospital care Abstract Objective : To compare effectiveness of patient care in hospital at home scheme with hospital care . Design : Pragmatic r and omised controlled trial . Setting : Leicester hospital at home scheme and the city 's three acute hospitals . Participants : 199 consecutive patients referred to hospital at home by their general practitioner and assessed as being suitable for admission . Six of 102 patients r and omised to hospital at home refused admission , as did 23 of 97 allocated to hospital . Intervention : Hospital at home or hospital inpatient care . Main outcome measures : Mortality and change in health status ( Barthel index , sickness impact profile 68 , EuroQol , Philadelphia geriatric morale scale ) assessed at 2 weeks and 3 months after r and omisation . The main process measures were service inputs , discharge destination , readmission rates , length of initial stay , and total days of care . Results : Hospital at home group and hospital group showed no significant differences in health status ( median scores on sickness impact profile 68 were 29 and 30 respectively at 2 weeks , and 24 and 26 at 3 months ) or in dependency ( Barthel scores 15 and 14 at 2 weeks and 16 for both groups at 3 months ) . At 3 months ' follow up , 26 ( 25 % ) of hospital at home group had died compared with 30 ( 31 % ) of hospital group ( relative risk 0.82 ( 95 % confidence interval 0.52 to 1.28 ) ) . Hospital at home group required fewer days of treatment than hospital group , both in terms of initial stay ( median 8 days v 14.5 days , P=0.026 ) and total days of care at 3 months ( median 9 days v 16 days , P=0.031 ) . Conclusions : Hospital at home scheme delivered care as effectively as hospital , with no clinical ly important differences in health status . Hospital at home result ed in significantly shorter lengths of stay , which did not lead to a higher rate of subsequent admission . Key messages The effectiveness of hospital at home schemes for avoiding hospital admission has not been tested in a trial In this study patients suitable for hospital at home care were r and omised to hospital at home or hospital care and followed up for three months There were no clinical ly or statistically significant differences in outcome as measured by the sickness impact profile 68 , Barthel index , Philadelphia geriatric morale scale , and EuroQol Length of stay in care and total days of care were about 45 % less for patients r and omised to hospital at home For patients who meet the admission criteria , hospital at home schemes can provide an effective and acceptable alternative to hospital BACKGROUND Organised specialist care for stroke improves outcome , but the merits of different methods of organisation are in doubt . This study compares the efficacy of stroke unit with stroke team or domiciliary care . METHODS A single-blind , r and omised , controlled trial was undertaken in 457 acute-stroke patients ( average age 76 years , 48 % women ) r and omly assigned to stroke unit , general wards with stroke team support , or domiciliary stroke care , within 72 h of stroke onset . Outcome was assessed at 3 , 6 , and 12 months . The primary outcome measure was death or institutionalisation at 12 months . Analyses were by intention to treat . FINDINGS 152 patients were allocated to the stroke unit , 152 to stroke team , and 153 to domiciliary stroke care . 51 ( 34 % ) patients in the domiciliary group were admitted to hospital after r and omisation . Mortality or institutionalisation at 1 year were lower in patients on a stroke unit than for those receiving care from a stroke team ( 21/152 [ 14 % ] vs 45/149 [ 30 % ] ; p<0.001 ) or domiciliary care ( 21/152 [ 14 % ] vs 34/144 [ 24 % ] ; p=0.03 ) , mainly as a result of reduction in mortality . The proportion of patients alive without severe disability at 1 year was also significantly higher on the stroke unit compared with stroke team ( 129/152 [ 85 % ] vs 99/149 [ 66 % ] ; p<0.001 ) or domiciliary care ( 129/152 [ 85 % ] vs 102/144 [ 71 % ] ; p=0.002 ) . These differences were present at 3 and 6 months after stroke . INTERPRETATION Stroke units are more effective than a specialist stroke team or specialist domiciliary care in reducing mortality , institutionalisation , and dependence after stroke |
13,869 | 27,034,016 | Analysis by MTC indicated that ablative techniques were typically more effective than topical interventions at completely clearing AGWs at the end of treatment .
The results generated by the MTC are in agreement with consensus opinion that ablative techniques are clinical ly more effective at completely clearing AGWs after treatment .
The results of the economic analysis suggest that podophyllotoxin 0.5 % solution is likely to represent a cost-effective first-line treatment option .
No treatment and podophyllin are unlikely to be considered cost-effective treatment options . | BACKGROUND Typically occurring on the external genitalia , anogenital warts ( AGWs ) are benign epithelial skin lesions caused by human papillomavirus infection .
AGWs are usually painless but can be unsightly and physically uncomfortable , and affected people might experience psychological distress .
The evidence base on the clinical effectiveness and cost-effectiveness of treatments for AGWs is limited .
OBJECTIVES To systematic ally review the evidence on the clinical effectiveness of medical and surgical treatments for AGWs and to develop an economic model to estimate the cost-effectiveness of the treatments .
More expensive effective treatments , such as CO2 laser therapy or surgery , may represent cost-effective second-line treatment options . | The complete treatment of anogenital warts has not been obtained with any combination of methods ; therefore , new methods are still under investigation . In this study the activity and side effects of imiquimod 5 % cream were investigated . The study group consisted of 23 male and 11 female volunteers and the control group of 9 male and 2 female volunteers . Patients applied the cream three times a week , every other day in the evenings for a period of 12 weeks . After the treatment , patients were regularly monitored for six months for recurrences . At the end of the study , 23 ( 69.7 % ) patients ( all of females and 54.5 % of males ) in the study group displayed a complete clearance , 9 patients displayed 50 - 90 % clearance and 1 patient displayed less than 50 % clearance . In the control group , only 1 patient displayed a complete clearance , 1 patient displayed 50 - 90 % clearance , and the other 8 patients showed no alteration in the lesions . These results were statistically significantly different ( p<0.01 ) . In 15 patients in the study group , no side effects were reported ; the most frequently seen side effects were erythema and erosion . In six patients that were observed for a period of six months , recurrences occurred . Imiquimod 5 % cream is a topically applied medicament that should be considered as an effective and reliable medical option in the treatment of anogenital warts Objective . To evaluate if new imiquimod formulations using a shorter treatment duration are safe and efficacious to treat anogenital warts . Methods . In two studies 534 women ≥12 years of age ( mean 33.4 ) with 2–30 warts ( mean 7.9 ) and total wart area ≥10 mm2 ( mean 166.3 ) were r and omized ( 1 : 2 : 2 ) to placebo ( 106 ) , imiquimod 2.5 % ( 212 ) or 3.75 % ( 216 ) creams applied once daily until complete clearance or a maximum of 8 weeks . Results . For placebo , imiquimod 2.5 % and 3.75 % , respectively , complete clearance of all warts was achieved in 14.2 % , 28.3 % , and 36.6 % of women ( intent-to-treat , P = 0.008 imiquimod 2.5 % , and P < 0.001 3.75 % versus placebo ) . Mean changes in wart counts were −10.7 % , −50.9 % , and −63.5 % ( per- protocol , P < 0.001 each active versus placebo ) and safety-related discontinuation rates 0.9 % , 1.4 % , and 2.3 % . Conclusions . Imiquimod 3.75 % applied daily for up to 8 weeks was well tolerated and superior to placebo in treating women with external anogenital warts OBJECTIVES The objectives of this study were to estimate the incidence of genital warts and treatment costs in women consulting gynaecologists in France in 2005 . PATIENTS AND METHODS A prospect i ve observational study was performed through a representative sample of gynaecologists . Investigators enrolled all patients seen with genital warts during a 2-month period . A question naire detailing socio-demographic characteristics , case description , patient 's clinical profile , past/ current management , and treatment of genital warts was completed by the investigators . RESULTS 212 gynaecologists participated in the study . Question naires were completed for 263 patients including 198 ( 75.3 % ) new cases , 53 ( 20.2 % ) recurrent cases and 12 ( 4.5 % ) resistant cases . The overall incidence was estimated at 228.9/100,000 ( female 15 - 65year old population ) corresponding to 47,755 cases annually managed by gynaecologists in France . The average treatment cost was 482.70euro for society and 342.40 euro for third-party payers . The annual direct cost of genital warts management was estimated at 23,051,339euro , of which 16,351,312euro was funded by the French health care system . DISCUSSION AND CONCLUSION The costs of treating genital warts are considerable . The introduction of a quadrivalent ( type 6,11,16,18 ) Human Papillomavirus vaccine including types responsible for 90 % of genital warts could potentially substantially reduce these costs The purpose of this double-blind , placebo-controlled , comparative study was to evaluate the specific clinical efficacy and tolerance of human leukocyte interferon-α ( 2 × l06 IU/g ) and podophyllotoxin 0.5 % incorporated in a hydrophilic cream to cure genital warts . Preselected Asian women ( n=60 ) aged 18–40 years ( mean 22.9 ) , with a clinical and biopsy-confirmed diagnosis of genital warts , harboring 322 lesions ( mean 5.36 ) were r and omly assigned to three parallel groups to receive one of the two test drugs or placebo . Each patient received a preceded tube ( 40 g ) containing either human leukocyte interferon-α , podophyllotoxin , or identically appearing placebo cream for 3 days ' usage . In addition to written instructions , each subject was shown how to apply a minimal amount of trial medication on their lesions thrice daily for 3 consecutive days per week ( maximum nine topical applications per week ) . Patients were examined on a weekly basis , and a cure was considered to be a biopsy-confirmed , total elimination of a lesion . Moreover , patients cured during the study period were spared further therapy , and were requested to return in 16 weeks to monitor for the occurrence of a relapse . The remaining patients ' empty tubes were collected , and similarly precoded replacement tubes were given to continue the treatment ; a total of 214 tubes were used . The study was scheduled for 16 weeks with 4 weeks of active treatment . Individuals were excluded from the study due to pregnancy , breast feeding , or the receiving of any type of antiviral therapy during the 4 weeks preceding enrollment . Better results were obtained with leukocyte interferon-α cream than with podophyllotoxin both in terms of the number of cured patients ( 18/20 vs. 12/20 , or 90 % vs. 60 % ; P<0.0285 ) and the number of eliminated lesions ( 105/110 ) vs. 87/108 , or 95.5 % vs. 80.5 % ; P<0.001 . In the placebo group 4/20 ( 20 % ) patients were cured , indicating lower results . Out of the 60 patients 51 ( 85 % ) complained of no drug-related symptomatic side effects . However , the most frequent non objective adverse symptoms experienced by the patients were mild tenderness 4/60 ( 6.6 % ) , burning sensation 3/60 ( 5 % ) , and transitory increase in body temperature ( > 38 ° C ) accompanied by headache and itching 2/60 ( 3.3 % ) . None of the patients suffering from these side effects elected to discontinue the study . The patients were evaluated for 1 year after the initial visit , and among the 34/60 ( 56.6 % ) cured patients two had a relapse after 9 months . In conclusion , the clinical results of this study demonstrate that leukocyte interferon-α ( 2 × l06 IU/g ) is more efficacious than 0.5 % podophyllotoxin and placebo in hydrophilic cream , and substantiates that along with mild , non objective , transient , localized , adverse symptoms , human leukocyte α-interferon therapy is more effective and better than podophyllotoxin in cream for curing genital warts in PURPOSE Genital warts are a highly prevalent and chronic sexually transmitted disease for which there is no completely satisfactory therapy . Conventional ablative therapy requires repeated treatment , often for months or years . This study was undertaken to evaluate the safety and efficacy of 0.5 % podofilox in patient-administered treatment of penile warts . PATIENTS AND METHODS Thirty-eight men with penile warts were r and omly assigned to double-blind , self-administration of 0.5 % podofilox solution or placebo , twice daily for 3 days per week for 4 weeks . Eleven podofilox and 15 placebo recipients with residual warts then received an additional 4 weeks of open-label treatment . RESULTS By the end of treatment , podofilox recipients had their mean wart number and area reduced to 15.9 % and 5.1 % of baseline values , compared to 97.4 % and 92.9 % in the placebo group ( p = 0.0001 ) . Local adverse reactions were more common in the podofilox group , but were transient . Complete disappearance of warts was observed in 25 ( 53.3 % ) of 45 treatment courses , including open-label treatment . Recurrences of warts after therapy were frequent . Only 21 % of patients remained free of warts 2 weeks after completing treatment , and subsequent recurrences were noted in all patients available for long-term follow-up , which is a common limitation of ablative therapy for genital warts . CONCLUSION Podofilox 0.5 % solution is effective in treating penile warts and is well tolerated in a self-administered regimen . Podofilox 0.5 % offers potential advantages in safety and cost over podophyllin resin therapy of genital warts BACKGROUND Genital warts are a well-recognized clinical entity and a disease of great antiquity that differ from skin warts both histologically and antigenically . It is a common sexually transmitted disease of high prevalence all over the world . Women are more likely to be unaware of such warts because it is harder for them to examine their genitalia . OBJECTIVE The purpose of this multicenter , double-blind , placebo-controlled study was to compare the clinical efficacy and tolerance of 0.3 % and 0.5 % podophyllotoxin in a cream emulsion ( castor oil , BP as vehicle ) to cure genital condylomata in women . METHODS Preselected ( n = 80 ) Asian females ( mean age 23.6 years ) , harboring 544 warts ( mean 6.8 in number ) , ranging from 1 to 9 mm in size ( mean 2.1 mm ) with biopsy-proven diagnosis of condylomata acuminata were r and omly allocated to three groups ( 30 + 30 + 20 ) . At home the patients applied the given trial medication themselves ( using the finger ) twice a day , for 3 consecutive days per week , and if not cured the same course was extended to 3 more weeks , in total 24 topical applications for 4 weeks . The patients were examined on a weekly basis , and a total regression of warts ( biopsy-proven ) was evaluated as complete cure . RESULTS By the end of the study , the placebo group ( 20 patients , bearing 124 warts ) did not show any regression or clinical efficacy , while 41/60 patients ( 68.3 % ) and 349/420 warts ( 83 % ) were cured in the 0.3 % and 0.5 % treatment groups ( placebo vs. active groups p < 0.001 ) . Patients using the 0.5 % active medication had substantially more eliminated warts ( 205/349 , 95.8 % ) than the 0.3 % group ( 70 % ) . Localized adverse symptoms were mild to moderate and were well tolerated by the patients with no dropout . Forty-three patients ( 53.8 % ) did not show any adverse reaction . The most frequent adverse symptoms were tenderness ( 23/80 , 28.8 % ) and burning sensation ( 14/80 , 17.5 % ) . Among 41/80 ( 51.25 % ) cured patients 4 had a relapse after 16 weeks . CONCLUSION Along with mild , tolerable side effects the study demonstrates that 0.5 % podophyllotoxin cream is more efficacious than 0.3 % ( p < 0.01 ) and can be considered as a reliable home-based treatment Background The approximately 1100 medical journals now active in China are publishing a rapidly increasing number of research reports , including many studies identified by their authors as r and omized controlled trials . It has been noticed that these reports mostly present positive results , and their quality and authenticity have consequently been called into question . We investigated the adequacy of r and omization of clinical trials published in recent years in China to determine how many of them met acceptable st and ards for allocating participants to treatment groups . Methods The China National Knowledge Infrastructure electronic data base was search ed for reports of r and omized controlled trials on 20 common diseases published from January 1994 to June 2005 . From this sample , a subset of trials that appeared to have used r and omization methods was selected . Twenty-one investigators trained in the relevant knowledge , communication skills and quality control issues interviewed the original authors of these trials about the participant r and omization methods and related quality -control features of their trials . Results From an initial sample of 37,313 articles identified in the China National Knowledge Infrastructure data base , we found 3137 apparent r and omized controlled trials . Of these , 1452 were studies of conventional medicine ( published in 411 journals ) and 1685 were studies of traditional Chinese medicine ( published in 352 journals ) . Interviews with the authors of 2235 of these reports revealed that only 207 studies adhered to accepted methodology for r and omization and could on those grounds be deemed authentic r and omized controlled trials ( 6.8 % , 95 % confidence interval 5.9–7.7 ) . There was no statistically significant difference in the rate of authenticity between r and omized controlled trials of traditional interventions and those of conventional interventions . R and omized controlled trials conducted at hospitals affiliated to medical universities were more likely to be authentic than trials conducted at level 3 and level 2 hospitals ( relative risk 1.58 , 95 % confidence interval 1.18–2.13 , and relative risk 14.42 , 95 % confidence interval 9.40–22.10 , respectively ) . The likelihood of authenticity was higher in level 3 hospitals than in level 2 hospitals ( relative risk 9.32 , 95 % confidence interval 5.83–14.89 ) . All r and omized controlled trials of pre-market drug clinical trial were authentic by our criteria . Of the trials conducted at university-affiliated hospitals , 56.3 % were authentic ( 95 % confidence interval 32.0–81.0 ) . Conclusion Most reports of r and omized controlled trials published in some Chinese journals lacked an adequate description of r and omization . Similarly , most so called ' r and omized controlled trials ' were not real r and omized controlled trials owing toa lack of adequate underst and ing on the part of the authors of rigorous clinical trial design . All r and omized controlled trials of pre-market drug clinical trial included in this research were authentic . R and omized controlled trials conducted by authors in high level hospitals , especially in hospitals affiliated to medical universities had a higher rate of authenticity . That so many non-r and omized controlled trials were published as r and omized controlled trials reflected the fact that peer review needs to be improved and a good practice guide for peer review including how to identify the authenticity of the study urgently needs to be developed Objectives : To evaluate the efficacy and cost effectiveness of self applied podophyllotoxin 0.5 % solution and podophyllotoxin 0.15 % cream , compared to clinic applied 25 % podophyllin in the treatment of genital warts over 4 weeks . Methods : We conducted a r and omised controlled trial in 358 immunocompetent men and women with genital warts of 3 months ’ duration or less . Results : In the principal analysis both podophyllotoxin solution ( OR 2.93 , 95 % CI 1.56 to 5.50 ) and podophyllotoxin cream ( OR 1.97 , 95 % CI 1.04 to 3.70 ) were associated with significantly increased odds of remission of all warts compared to podophyllin . We performed two further analyses . When subjects defaulting from follow up were assumed to have been cured odds of remission of all warts were also significantly increased both for podophyllotoxin solution ( OR 3.04 , 95 % CI 1.68 to 5.49 ) and for podophyllotoxin cream ( OR 2.46 , 95 % CI 1.38 to 4.40 ) . When subjects defaulting from follow up were assumed not to have been cured odds of remission of all warts were significantly increased for podophyllotoxin solution ( OR 1.92 , 95 % CI 1.13 to 3.27 ) , but not for podophyllotoxin cream ( OR 1.17 , 95 % CI 0.69 to 2.00 ) . Local side effects were seen in 24 % of subjects , and recurrence of warts within 12 weeks of study entry in 43 % of all initially cleared subjects , without statistically significant differences between the treatment groups . Direct , indirect , and total costs were similar across the three treatment groups . Podophyllotoxin solution was the most cost effective treatment , followed by podophyllotoxin cream , with podophyllin treatment being the least cost effective . Conclusions : Self treatment of anogenital warts with podophyllotoxin showed greater efficacy and cost effectiveness than clinic based treatment with podophyllin Abstract Objective : To evaluate the cost-effectiveness and treatment-cost impact of sinecatechins ( Veregen * ) as first-line therapy against its principal comparator , imiquimod ( Aldara† ) , in the treatment of external genital warts ( EGWs ) . Method : A two-stage decision model is proposed to compare sinecatechins with its principal comparator , imiquimod , as a first-line topical therapy in the treatment of EGWs . The model utilizes estimates of sustained clearance from two pivotal sinecatechins trials and from a systematic literature review for imiquimod . Re source inputs are : ( 1 ) trial-based estimates of average drug utilization and ( 2 ) CPT ( Current Procedural Terminology ) codes describing anticipated office visits and utilization of second-line ablative procedures . The analysis considers : ( 1 ) comparative costs of achieving a successful outcome with sinecatechins versus imiquimod , and ( 2 ) comparative cost – consequences of sinecatechins versus imiquimod . As a modeled approach to evaluating comparative product effectiveness , the cl aims made reflect the structure of the model , which focuses on topical products as first-line therapy in EGW interventions and in its reliance on estimates of sustained clearance from pivotal r and omized clinical trials ( RCTs ) . Sustained clearance in this context being defined as the proportion of patients who report initial wart clearance over the RCT period corrected for subsequent recurrence . Results : As first-line therapy , sinecatechins dominates imiquimod as a lower cost treatment with a higher sustained clearance rate ( 51.9 vs. 40.6 % ) . First-line average cost of treatment with sinecatechins is $ 774 compared to imiquimod at $ 930 . Cost per successful outcome with sinecatechins is $ 1,492 , which is lower than $ 2,289 for imiquimod . Taking account of patients failing first-line therapy moving to a second-line ablative therapy yields an average cost of treatment for patients initiated to sinecatechins of $ 943 and $ 1,138 for those initiated to imiquimod . A sensitivity assessment confirmed the position of sinecatechins within the decision-model framework . Conclusion : Sinecatechins yields a lower cost of treatment compared to imiquimod in the treatment of EGW . It also offers cost savings to healthcare systems . This conclusion should be qualified by the limitations of the decision framework within which the assessment has been made . The model focuses on topical preparations as first-line therapies , with estimates of sustained clearance taken from pivotal RCTs . Treatment cost estimates are generated independently , but reflect current product and ancillary costs The clinical effect of imiquimod stems from cytokine-induced activation of the immune system . A r and omized study was conducted to study the efficacy and safety of daily applications of 5 % imiquimod cream in female patients with external genital warts and molluscum contagiosum ( MC ) . The clearance rate of lesions was 75 % in genital MC patients and 50 % in patients with genital warts . Erythema was the commonest adverse reaction seen in 24 % patients with the use of 5 % imiquimod . Other side effects were excoriation seen in 16 % patients , erosions in 10 % patients , excoriation in 6 % patients and pain was seen in 4 % patients Forty-two male patients with ano-genital warts were r and omly allocated to a single-blind study of cryotherapy versus electrocautery . There was no significant difference in the success rates of these two forms of treatment in patients followed for three months . Cryotherapy was qualitatively much more acceptable to the patients than electrocautery . It seems particularly suited to patients with widely scattered warts who are unable to attend for regular treatment BACKGROUND Genital warts are a common sexually transmitted disease caused by human papillomavirus . Imiquimod is a novel immune-response modifier capable of inducing a variety of cytokines , including interferon alfa , tumor necrosis factor-alpha , as well as interleukins 1 , 6 , and 8 . In animal models imiquimod has demonstrated antiviral , antitumor , and adjuvant activity . In vitro , imiquimod has no antiviral or antitumor activity . OBJECTIVE Our purpose was to determine the safety and efficacy of topical imiquimod for the treatment of external genital warts . METHODS This prospect i ve double-blind , placebo-controlled , parallel design clinical trial was performed in three outpatient centers , a public health clinic , a university-based clinic , and a private practice . One hundred eight patients with external genital warts ( predominantly white men ) were entered into the trial . Fifty-one patients were r and omly selected to receive 5 % imiquimod cream ; 57 patients were r and omly chosen to receive placebo cream . Study medication was applied three times weekly for up to 8 weeks . Patients whose warts cleared completely were observed for up to 10 weeks to determine recurrence rates . RESULTS In the intent-to-treat analysis , the warts of 37 % ( 19 of 51 ) of the imiquimod-treated patients and 0 % ( 0 of 57 ) of the placebo group cleared completely ( p < 0.001 ) . In addition , many patients experienced a partial response . A reduction in baseline wart area of 80 % or more was observed in 62 % of imiquimod-treated patients ( 28 of 45 ) and 4 % of the placebo group ( 2 of 50 ) ( p < 0.001 ) ; a 50 % reduction or more in wart area was noted in 76 % of imiquimod-treated patients ( 34 of 45 ) and 8 % of placebo recipients ( 4 of 50 ) ( p < 0.001 ) . Of imiquimod-treated patients whose warts cleared completely and who finished the 10-week follow-up period , 19 % ( 3 of 16 ) experienced recurrences of warts . Imiquimod-treated patients experienced a significantly greater number of local inflammatory reactions than the placebo group . Symptoms and signs associated with the local inflammatory reactions included itching ( 54.2 % ) , erythema ( 33.3 % ) , burning ( 31.3 % ) , irritation ( 16.7 % ) , tenderness ( 12.5 % ) , ulceration ( 10.4 % ) , erosion ( 10.4 % ) , and pain ( 8.3 % ) . There were no differences in systemic reactions or laboratory abnormalities between treatment groups . CONCLUSION Topical 5 % imiquimod cream appears to have a significant therapeutic effect in the treatment of external genital warts Genital condylomata acuminata are nonmalignant human papillomavirus (HPV)-induced tumors in which HPV types 6 and 11 are most commonly found . Usual treatments for condylomata acuminata are nonspecific and are based on the destruction or removal of infected tissue . These procedures are often painful and are characterized by a high relapse rate . We report here what is to our knowledge the first double-blind , placebo-controlled study of the use of cidofovir , a nucleotide analogue , for the treatment of genital papillomavirus infections . Thirty patients were enrolled in the study ; 19 received cidofovir , and 11 received placebo . The median number of warts and the median baseline wart area were comparable for both groups . Nine ( 47 % ) of 19 patients in the cidofovir group had a complete response ( total healing ) , compared with 0 of the patients in the placebo group ( P=.006 ) . None of the patients in the cidofovir group experienced progression of the disease , compared with 5 ( 45 % ) of 11 patients in the placebo group . The side effects recorded for both groups were comparable Summary : Sixty women with genital warts were r and omly allocated to treatment with either weekly application of 20 % podophyllin solution or self-treatment with 0.5 % podophyllotoxin cream twice daily for three days in weekly intervals . After a maximum of 4 treatment cycles a final assessment was carried out after 3 months . Primary clearance after termination of treatment was 82 % for podophyllotoxin and 59 % for podophyllin solution . After excluding relapses at the 3-month follow-up , final clearance for podophyllotoxin ( 71 % ) was significantly better ( P < 0.05 ) than that for podophyllin solution ( 48 % ) . The total frequency of warts eradicated was 94 % with podophyllotoxin and 74 % with podophyllin solution ( P < 0.001 ) . Local adverse effects were generally mild or moderate . Podophyllotoxin cream provides a mode of easy application for women with external genital warts and had in this study a significantly better effect than podophyllin solution OBJECTIVE --To evaluate the efficacy-safety ratio of a new topical podophyllotoxin cream 0.5 % compared with podophyllotoxin solution 0.5 % ( Condyline ) in male patients with genital warts . METHODS --In an observer-blinded controlled study a total of 136 and 133 wart lesions were treated with podophyllotoxin cream 0.5 % and podophyllotoxin solution 0.5 % , respectively . The preparations were applied twice daily for 3 days , repeated with 4 days intervals for a minimum of two and a maximum of four treatment cycles . RESULTS --At the conclusion of the study ( 8 weeks after completion of therapy ) a significant reduction in mean wart area was observed in both the cream group ( 87.7 , SD 8.4 to 20.6 , SD 2.7 ) and in the solution group ( 92.3 , SD 7.5 to 21.5 , SD 2.8 ) ( p < 0.01 ) . At the same time all treated warts had completely cleared in 63 % of patients in both study groups . Mild to moderate side effects occurred to the same extent in both podophyllotoxin cream and podophyllotoxin solution recipients . CONCLUSION --We conclude that podophyllotoxin 0.5 % administered in a cream formulation does not give additional clinical benefits when compared with podophyllotoxin solution 0.5 % in male patients with external genital warts Background Medical therapy for genital warts remains suboptimal . The topical interferon and cytokine inducer , imiquimod , has been proved effective for the treatment of external genital and perianal warts , but there is a substantial difference in the response rates between men and women . When 5 % imiquimod cream is applied three times a week up to 16 weeks , approximately two thirds of women treated with imiquimod achieve complete clearance of genital warts , whereas only about one third of men clear completely . Goal This study was undertaken to determine whether more frequent application of topical imiquimod cream would improve the rate of genital wart clearance in men . Study Design A r and omized treatment trial involving adult men with biopsy-proven genital warts was conducted at nine centers in the United States and Canada using four different application frequencies . Results Complete clearance rates during the 16-week treatment period were as follows for the different imiquimod treatment frequencies : three times a week ( 35 % ) , once daily ( 28 % ) , twice daily ( 24 % ) , and three times a day (27%)(P = 0.88 ) . The four treatment groups all showed comparable reductions in the total lesion area , with a median of more than a 90 % reduction in the lesion area by the end of treatment . There was a significant increase in the incidence and severity of local skin reactions including erythema , vesicle formation , ulceration , and excoriation as the dosing frequency increased from three times a week to three times a day . Conclusions In this study , the optimal dosage regimen was the approved three times a week regimen . More frequent application ( up to three times a day ) did not improve clearance and was associated with an increase in local adverse events 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 determine the safety and efficacy of a new gel formulation of podofilox in the treatment of anogenital warts . DESIGN Double-blind , r and omized , multicenter , vehicle-controlled investigation . SETTING Private dermatology practice s , university clinics ( dermatology , gynecology , and infectious diseases ) , and contract research organizations . PATIENTS Three hundred twenty-six patients with anogenital warts . MAIN OUTCOME MEASURE Number of patients with clearing of all treated warts ( treatment success ) . RESULTS The 0.5 % podofilox gel was significantly better than vehicle gel for successfully eliminating and reducing the number and size of anogenital warts . In the intent-to-treat population , 62 ( 37.1 % ) of 167 patients treated with 0.5 % podofilox gel had complete clearing of the treated areas ( treatment successes ) compared with 2 ( 2.3 % ) of 86 patients who had clearing of warts with the vehicle gel ( P < .001 ) after 4 weeks . Nineteen additional patients treated with 0.5 % podofilox gel and 2 patients treated with vehicle gel had clearing of warts with continued treatment up to 8 weeks . After 8 weeks , 35.9 % of the baseline anogenital warts treated with 0.5 % podofilox gel remained ; this was significantly fewer than in the vehicle-treated group ( 88.4 % of the baseline number ) ( P = .001 ) . The 0.5 % podofilox gel was generally well tolerated , with predominantly mild or moderate local adverse reactions occurring in the majority of patients . Only 7 patients ( 3.2 % ) , all receiving 0.5 % podofilox gel , discontinued study treatment because of drug-related local reactions . CONCLUSIONS The results demonstrated that 0.5 % podofilox gel is safe and significantly more effective than vehicle gel in the treatment of anogenital warts OBJECTIVE : To compare the effectiveness and cost of self treatment of penile warts with a commercial preparation of podophyllotoxin 0.5 % ( PDX 0.5 % ) with podophyllin 0.5 % and podophyllin 2.0 % source d from Podophyllum emodii . DESIGN : A prospect i ve double blind r and omised study . SUBJECTS : 315 patients with penile warts attending two departments of genitourinary medicine . MAIN OUTCOME MEASURES : Absence of warts , cessation of treatment due to severe side effects at 5 weeks . RESULTS : Of the 315 patients , 244 conformed to the protocol . Analysis was on an intention to treat basis . At 5 weeks no significant differences were found in the extent of healing of warts or in side effects for the three treatment groups . The costs of drug treatment ( excluding staff time ) are at least pounds 10.00 less for podophyllin than podophyllotoxin . A fourfold variation in the active constituents of the podophyllin preparations did not produce appreciably different clinical responses . In a sub analysis no evidence of deterioration in effectiveness of podophyllin over time was demonstrated . CONCLUSIONS : Penile warts in selected cases can be safely treated with 0.5 - 2.0 % podophyllin self applied by the patient at a fraction of the cost of commercially available podophyllotoxin . The shelf life of the podophyllin extracts is at least 3 months . These findings may be especially relevant in countries where re sources for health care are limited Objective To evaluate the efficacy of surgical-cidofovir ( SCT ) , surgical ( ST ) and cidofovir ( CT ) treatment of genital warts in HIV-infected patients . Design Open r and omized prospect i ve pilot study . Setting Out patients attending the sexually transmitted disease service of the II Dept of Infectious Diseases , L Sacco Hospital , Milan-Italy . Patients Consenting HIV-positive patients with anal – genital warts recruited from January 2000 to March 2001 . Interventions Three treatment arms : surgical excision by electrocautery , topical 1 % cidofovir-gel ( 5 days per week , maximum 6 weeks ) and electrocautery – cidofovir treatment with 1 % cidofovir-gel applied within 1 month of surgical treatment ( 5 days per week for 2 weeks ) . Main outcome measures Rate of wart clearance and time and rate of relapses within a 6-month follow-up period . Results Complete response was achieved in 93.1 % of 29 patients treated by ST , 76.2 % of 26 treated by CT and in 100 % of 19 patients treated by SCT ( P = 0.0033 ) . The relapse rate in 49 patients followed-up was 73.68 % in ST , 35.29 % in CT and 27.27 % in SCT patients ( P = 0.018 ) . Median time to relapses in ST patients was 66 days ( Kaplan – Meyer , P = 0.0012 ) . Human papillomavirus DNA was cleared in 52.63 % of 19 patients evaluated . The rate of clearance of high risk and low risk genotypes was 0 % and 57.14 % 25 % and 50 % 100 % and 71.42 % in ST , CT and SCT patients , respectively . Conclusions A combination of surgical and medical treatment was most effective in clearing lesions completely and in reducing the relapse rate . Human papillomavirus DNA clearance can be attributed to the antiviral effect of cidofovir and could explain the low relapse rate observed . Larger studies are required to determine the most appropriate medical treatment for viral eradication after surgery Background and Objectives : To evaluate and compare the efficacy and adverse effects of trichloracetic acid and cryotherapy ( using liquid nitrogen ) in the treatment of external genital warts . Study Design : Eighty‐six patients were enrolled into a r and omized clinical trial in the Genitourinary Medicine Department of the Coventry and Warwickshire Hospital ( Coventry ) between November 1990 and June 1991 . External genital warts were treated with either trichloracetic acid or cryotherapy ( using liquid nitrogen ) on a once weekly basis . They received up to six treatments of either therapy . Results : Complete clearance of warts in patients who received up to six treatments of cryotherapy were observed in 86 % of cases and in 70 % of patients who received up to six treatments of trichloracetic acid . Thirty percent of patients who were treated with trichloracetic acid developed ulcerations at the site of its application . Conclusion : In this study we found that cryotherapy ( using liquid nitrogen ) is more effective than that of trichloracetic acid for the treatment of external genital warts . It is also less likely to cause ulceration Seventy-three patients with anogenital warts were r and omly allocated to a double-blind comparison of treatment with trichloracetic acid ( 50 % ) and podophyllin ( 25 % ) versus podophyllin ( 25 % ) alone . There was no significant difference in the resolution of warts in the two treatment groups among patients followed for three months . Of patients free of warts at six weeks , treatment with trichloracetic acid/podophyllin required significantly fewer applications ( mean 2.9 ) compared with podophyllin alone ( mean 4.0 ) . Five ( 17 % ) patients in the former group reported side effects but none in the latter group Four hundred and fifty patients were enrolled into a r and omised clinical trial in a public sexually transmitted diseases clinic to evaluate the efficacy of podophyllin , cryotherapy , and electrodesiccation for treatment of external genital warts . Complete clearance of warts was observed in 41 % , 79 % , and 94 % of patients who received up to six weekly treatments of podophyllin , cryotherapy , and electrodesiccation , respectively . Relapses occurred in 25 % of all patients , yielding 3 month clearance rates of 17 % , 55 % , and 71 % for podophyllin , cryotherapy , and electrodesiccation , respectively . Wart volume and duration did not influence treatment outcome . Response to therapy was greater in women than in men , and did not differ by treatment modality . Electrodesiccation and cryotherapy were more effective than podophyllin for the treatment of external genital warts , but none of these three treatments were highly successful In a double-blind , placebo-controlled study , self-treatment with a 0.5 % podophyllotoxin cream was evaluated among 60 women afflicted solely with outer vulvoanal warts ; 12 women received treatment with placebo cream and 48 women with active substance , administered twice daily in 3-day cycles once weekly for up to 3 weeks . Patients who were not completely cured after three cycles were classified as treatment failures . Four patients treated with podophyllotoxin cream were excluded : two were considered drop-outs , another patient was concurrently afflicted with intraanal warts , and a fourth patient refused further therapy with the cream due to the severity of local side effects occurring from the first course of therapy . Of the remaining 44 patients treated with active substance , the primary cure rates were 43 % , 66 % , and 91 % after 1 , 2 , and 3 treatment cycles , respectively . Within a 3-month follow-up period , 6 ( 14 % ) patients who were originally considered cured exhibited some degree of either " recurrence " or " reoccurrence " . Thus , a complete and permanent cure from podophyllotoxin cream occurred in 38 out of 44 patients ( 77 % ) . Placebo lacked therapeutic influence . A slight-to-moderate tenderness , pain , burning , or all of the above in the treated areas was noted by more than 60 % of the women who were treated with the podophyllotoxin cream BACKGROUND We evaluated the impact of a quadrivalent human papillomavirus ( HPV ) vaccine on infection and cervical disease related to 10 nonvaccine HPV types ( 31 , 33 , 35 , 39 , 45 , 51 , 52 , 56 , 58 , and 59 ) associated with > 20 % of cervical cancers . The population evaluated included HPV-naive women and women with preexisting HPV infection and /or HPV-related disease at enrollment . METHODS Phase 3 efficacy studies enrolled 17,622 women aged 16 - 26 years . Subjects underwent cervicovaginal sampling and Pap testing on day 1 and then at 6 - 12-month intervals for up to 4 years . HPV typing was performed on sample s from enrollment and follow-up visits , including sample s obtained for diagnosis or treatment of HPV-related disease . All subjects who received 1 dose and returned for follow-up were included . RESULTS Vaccination reduced the rate of HPV-31/33/45/52/58 infection by 17.7 % ( 95 % confidence interval [ CI ] , 5.1 % to 28.7 % ) and of cervical intraepithelial neoplasia ( CIN ) 1 - 3 or adenocarcinoma in situ ( AIS ) by 18.8 % ( 95 % CI , 7.4 % to 28.9 % ) . Vaccination also reduced the rate of HPV-31/58/59-related CIN1 - 3/AIS by 26.0 % ( 95 % CI , 6.7 % to 41.4 % ) , 28.1 % ( 95 % CI , 5.3 % to 45.6 % ) , and 37.6 % ( 95 % CI , 6.0 % to 59.1 % ) , respectively . Although a modest reduction in HPV-31/33/45/52/58-related CIN2 or worse was observed , the estimated reduction was not statistically significant . CONCLUSIONS These cross-protection results complement the vaccine 's prophylactic efficacy against disease associated with HPV-6 , -11 , -16 , and -18 . Long-term monitoring of vaccinated population s are needed to fully ascertain the population -based impact and public health significance of these findings . TRIAL REGISTRATION Clinical Trials.gov identifiers : NCT00092521 , NCT00092534 , and NCT00092482 Background Treatment options for anogenital warts in patients with HIV-1 are unsatisfactory because they fail to eradicate latent human papillomavirus . Goal To determine tolerability and efficacy of topical 1 % cidofovir cream for the treatment of external anogenital warts in HIV-infected patients . Study Design A r and omized , placebo-controlled , single-blind , crossover pilot study of either 1 % cidofovir cream or placebo applied once daily 5 days a week for 2 weeks followed by 2 weeks of observation was performed . Results Six patients were r and omized to 1 % cidofovir cream and six to placebo . The latter patients eventually received 1 % cidofovir cream . Thus , 12 treatment rounds of cidofovir were compared with six rounds of placebo . A reduction of more than 50 % in the total wart area achieved by seven cidofovir treatments ( 58 % ) , as compared with no placebo regimen ( P = 0.02 ) . Local reactions occurred in 10 of the 12 patients treated with cidofovir , as compared with 0 of the 6 subjects in the placebo group ( P < 0.001 ) . Conclusions For the initial clearance of anogenital warts in HIV-infected patients , 1 % cidofovir cream is significantly more effective than vehicle cream . Local mucosal erosion is a common side effect OBJECTIVE --To evaluate the clinical efficacy of a 0.15 % and a 0.3 % cream formulation of podophyllotoxin in comparison with the 0.5 % solution in the treatment of condylomata acuminata and to compare the treatment modalities regarding side effects . DESIGN --The study was design ed as an open r and omised trial . Ninety male patients with signs of penile HPV infection , with either acuminate or papular lesions , were r and omised into three parallel treatment groups . The study medication comprised 0.15 % and 0.3 % cream and 0.5 % solution of podophyllotoxin . The patients treated themselves twice daily for three consecutive days and if total regression of the warts was not achieved after this first treatment cycle , further treatment cycles at 7-day intervals were to be repeated up to a maximum of four treatments . SETTING --The study was carried out in three outpatient clinics : two STD clinics , Department of Dermatology and Venereology , University Hospital ( 45 patients ) and Institut Antoine Fournier , Paris ( 30 patients ) , and one military hospital , S1/FO 47/48 , Sjukhusenheten , Enköping ( 15 patients ) . RESULTS --Statistical evaluation of the treatment effect was based on a " Response rate " calculation at each visit . The number of completely responding patients after the first , second , third and fourth cycle were 40 ( 44 % ) , 61 ( 68 % ) , 67 ( 74 % ) and 70 ( 78 % ) , respectively . There was no statistically significant difference between the three treatments after four treatment cycles . However , the 0.15 % cream had a significantly slower onset of efficacy as compared with the 0.3 % cream and 0.5 % solution . Adverse effects were less severe and less frequent with the 0.15 % cream than with the other treatment modalities . Severe adverse effects were reported by 12 patients , of whom two were treated with 0.15 % cream , five with 0.3 % cream and five with 0.5 % solution . Thirty-one patients were completely free from adverse effects . CONCLUSION --In this open r and omised study with three parallel treatment groups , two cream formulations of 0.15 % and 0.3 % podophyllotoxin and a 0.5 % solution of the same drug all showed an equally good response rate after four treatment cycles . Reported adverse effects were few and mild . The convenience of having different formulations to offer when prescribing treatment for condylomata must be considered Podophyllotoxin solution 0.5 is licensed for use in the treatment of condylomata acuminata genital warts in men in a number of European countries . In some countries , approval also extends to treatment of genital warts in women . This controlled r and omized prospect i ve study evaluated the efficacy and safety of a cream formulation of podophyllotoxin at 2 concentrations 0.15 and 0.3 , using 0.5 podophyllotoxin solution as a reference treatment . Two separate studies were initiated , to assess the 3 treatment groups in a male patients , and b female patients . Statistical evaluation was based on a ' response rate ' calculated at each clinic visit . The mean ' response rates ' in the male patient study at 4 weeks were 75.1 , 79.0 and 85.6 in the 0.15 cream , 0.3 cream and 0.5 solution groups , respectively . The corresponding ' response rates ' for the female patient study were 86.2 , 92.6 , and 93.1 , respectively . The relapse rates for both male and female patients were 6.0 in the 0.15 cream group , 8.6 in the 0.3 cream group and 8.6 in the 0.5 solution group . The results show that there were no statistically significant differences between the 3 treatments with regard to both efficacy and safety . This was true for both the male and female patient groups Objectives : To determine the average cost of a case of genital warts , for both males and females , with a view to informing the current debate as to which Human papillomavirus vaccine would have maximum cost-effectiveness in the Irish population . Methods : Contact time between patients and healthcare professionals was prospect ively measured at five genitourinary medicine clinics in the south-west of Irel and , over a period of 3 weeks . By identifying all those with genital warts , it was possible to calculate the proportion of total time taken by patients with this condition , and from this to calculate a cost per incident case , by gender . Results : A total of 25.5 % of attendances were for genital warts , and these patients used 26.2 % of total clinic time ( CI 25.4 to 27.0 % ) . The average cost calculated for genital warts was € 335 per incident case , and by gender € 300 per male case and € 366 per female case . Conclusions : There are considerable costs associated with the treatment of genital warts , with female cases representing a higher cost than males . By vaccinating with the quadrivalent HPV vaccine , there are significant savings to be made The efficacy and safety of topical treatment for external condylomata acuminata with either self-applied 0.5 % podophyllotoxin ( PT ) or hospital-applied 25 % podophyllin ( PODO ) solution was compared in 138 males and 67 females in an open multicentre study . After one week of treatment , wart clearance was observed in 53 % of males and 37 % of females in the PT group as compared with 19 % of males and 19 % of females in the PODO group ( P < 0.001 in males ; P = 0.13 in females ) . At 5 weeks after commencing treatment , clearance of warts had been achieved in 86 % males and 72 % females in the PT group as compared with 78 % of males and 62 % females in the PODO group ( P = 0.08 in males ; P = 0.14 in females ) . Treatment had cleared 81 % of 180 treated sites in all PT recipients as compared with 61 % of 95 treated sites in all PODO recipients ( P < 0.001 ) . The increased speed of action of PT was associated with an increased incidence of symptoms and signs of inflammation at treatment sites in both males and females ( P < 0.001 ) . These were generally mild , did not interfere with continuing treatment , and were more frequent in those patients whose warts were eradicated most rapidly . Home-based treatment with 0.5 % podophyllotoxin lotion in appropriately instructed patients of either sex is superior in efficacy to outpatient applied 25 % podophyllin and has the potential to reduce the number of hospital attendances required in genital wart eradication Background : Little non-clinic-based data are available on incident genital warts rates and related healthcare use . Goal : The goal of this study was to describe the incidence and predictors of genital warts and associated healthcare utilization patterns among a group of privately insured patients in the United States . Study : Health cl aims were evaluated prospect ively from 5,914,107 privately insured individuals . Results : The rate of new genital warts cl aims per 100,000 person-years at risk , age-st and ardized to the 2001 U.S. privately insured population , increased from 117.8 in 1998 to 205.0 in 2001 . The highest rates were among 20- to 29-year-olds . The majority of cl aims came from dermatology and obstetrics/gynecology . Conclusions : The incidence of genital warts , as measured by the rate of new cl aims , appears to be rising . Age associations with the rate of new genital warts cl aims differed by gender ; these associations may be influenced by changes in health-seeking behavior , potentially driven by health awareness One hundred and forty male patients with ano-genital warts were r and omly allocated to a double-blind study of 10 % and 25 % podophyllin in tincture of benzoin compound . One hundred and nine patients attended for a three-month period of surveillance . Only 24 ( 22 % ) patients were free of warts after having podophyllin treatment alone , 12 each after treatment with 10 % and 25 % podophyllin . There was no significant difference in the number of applications needed with each treatment . Neither hypersensitivity nor chemical ulceration occurred Purpose Despite the increasing incidence of condylomata acuminate , optimal treatment of anal warts is still undecided . This prospect i ve , r and omized study was design ed to compare the efficacy of combined argon plasma coagulation and imiquimod cream vs. argon plasma coagulation alone in the management of intra-anal warts . Methods From October 2002 to March 2005 , 49 patients with intra-anal warts were r and omly assigned to argon plasma coagulation plus imiquimod cream ( n = 24 ) vs. argon plasma coagulation alone ( n = 25 ) . Therapeutic sessions were repeated until the elimination of the warts . Efficacy of therapy was defined as the time needed for eradication . All patients were followed up for a mean period of 12 months for signs of recurrence . Results Elimination of warts was achieved earlier in patients receiving combination therapy compared with those receiving monotherapy with argon plasma coagulation ( 62.5 ± 5.4 days vs. 91.2 ± 6.4 days ; P = 0.0016 ) . A subgroup analysis performed in HIV-positive patients showed similar results ( combination therapy 95 ± 22.6 days ; monotherapy 124.3 ± 20.7 days ; P = 0.033 ) ; however , in HIV-positive patients warts were eradicated later compared with HIV-negative patients ( 110.8 ± 25.7 days vs. 65 ± 25.4 days ; P < 0.0001 ) . No major complications were observed in our study population . After the follow-up period , recurrence of warts was evident in 22.7 percent of patients in the combination group compared with 34.7 percent of patients in the monotherapy group ( P = 0.51 ) . Recurrence was significantly higher in HIV-positive patients compared with HIV-negative patients ( P = 0.0039 ) . Conclusions Combination therapy with argon plasma coagulator plus imiquimod cream results in earlier clearance of intra-anal warts in both immunocompetent and immunocompromised patients ; however , it does not affect the rate of recurrence BACKGROUND The incidence of overt genital warts , a common sexually transmitted disease of high prevalence , has been on the rise for the last few years . The infection is caused by several types of human papillomaviruses ( HPVs ) , some of which have been accepted as a factor in the pathogenesis of genital squamous-cell carcinomas . OBJECTIVE The aim of this double-blind , placebo-controlled study was to compare and evidence differences in clinical efficacy and tolerance between human leukocyte interferon-alpha ( 2 x 10(6 ) IU/g ) and podophyllotoxin ( 0.5 % ) , incorporated in a hydrophilic cream base to cure genital warts in Asian males . METHODS Sixty patients , circumcised , who ranged in age from 18 to 40 years ( mean 25.0 ) , diagnosed with the evidence of penoscopy and HPV DNA ( Southern dot blot ) as harboring 396 lesions ( mean 6.6 ) , were r and omized to three parallel groups . Each subject was allocated a precoded tube ( 40 g ) containing one of two trial preparations or matching placebo for 3 days ' ( consecutive ) usage , thrice daily . The study lasted 16 weeks with 4 weeks of active treatment . The patients were examined on a weekly basis , and a clinical ly and HPV-DNA-confirmed total regression of lesions was recorded as cured . Patients cured during the treatment were spared further therapy and were requested to visit us as scheduled for post study follow-up . RESULTS Findings indicated that patients treated with leukocyte interferon-alpha cream had shown comparatively better results than the podophyllotoxin-treated group ( 90 vs. 55 % , p < 0.0285 ) or the placebo group ( 15 % ) . Mild and transient localized erythema ( 8.3 % ) , burning sensation ( 6.6 % ) and transitory increase in body temperature ( > 38 degrees C ; 6.6 % ) were the most frequent adverse symptoms with no dropout . The study was followed up for 1 year , and out of 32/60 ( 53.3 % ) cured patients 3 had a relapse after 10 months . CONCLUSION Leukocyte interferon-alpha ( 2 x 10(6 ) IU/g ) has shown comparatively better results than 0.5 % podophyllotoxin and placebo in a hydrophilic cream base , thus leukocyte interferon-alpha in cream may provide an alternative and effective regimen to treat genital warts in males OBJECTIVE To assess the safety of imiquimod , an immune response modifier , in the topical treatment of external anogenital warts in HIV-infected patients . SETTING Clinical sites in the United Kingdom ( eight ) and the United States ( five ) . DESIGN A prospect i ve , r and omized , double-blind , vehicle-controlled study of imiquimod 5 % cream or vehicle applied for 8+/-2 h three times per week for a maximum of 16 weeks in HIV-seropositive males ( n = 97 ) and females ( n = 3 ) aged 18 years or more with clinical ly diagnosed external anogenital warts , CD4 T lymphocyte count of > or = 100 x 10(6 ) cells/l and Karnofsky score > or = 70 . MAIN OUTCOME MEASURES Safety was assessed through the incidence and severity of local skin reactions and other adverse events , and through clinical laboratory tests . Wart clearance was documented by two-dimensional measurements of warts and by photography . RESULTS Among the patients treated with imiquimod ( n = 65 ) and vehicle ( n = 35 ) , the most common local skin reaction was erythema , ( 41.9 and 26.7 % , respectively ) and the incidence of patients reporting at least one adverse event was 69.2 and 65.7 % , respectively . No clinical ly meaningful differences or changes in laboratory values were observed between treatment groups , nor were drug-related adverse effects observed in regard to HIV disease . While there was no significant difference between treatment groups in the number of patients who totally cleared their baseline warts ( imiquimod 11 % versus vehicle 6 % , P = 0.488 ) , more imiquimod-treated patients experienced a > or = 50 % reduction in baseline wart area ( 38 % versus 14 % , P = 0.013 ) . CONCLUSION Most local skin reactions were mild and no adverse effects on HIV disease were observed . Topically applied imiquimod 5 % cream reduced wart area and may have clinical utility in treating external anogenital warts in some HIV-infected patients BACKGROUND The aim of this interim analysis of a large , international phase III study was to assess the efficacy of an AS04 adjuvanted L1 virus-like-particle prophylactic c and i date vaccine against infection with human papillomavirus ( HPV ) types 16 and 18 in young women . METHODS 18,644 women aged 15 - 25 years were r and omly assigned to receive either HPV16/18 vaccine ( n=9319 ) or hepatitis A vaccine ( n=9325 ) at 0 , 1 , and 6 months . Of these women , 88 were excluded because of high- grade cytology and 31 for missing cytology results . Thus , 9258 women received the HPV16/18 vaccine and 9267 received the control vaccine in the total vaccinated cohort for efficacy , which included women who had prevalent oncogenic HPV infections , often with several HPV types , as well as low- grade cytological abnormalities at study entry and who received at least one vaccine dose . We assessed cervical cytology and subsequent biopsy for 14 oncogenic HPV types by PCR . The primary endpoint -- vaccine efficacy against cervical intraepithelial neoplasia ( CIN ) 2 + associated with HPV16 or HPV18 - -was assessed in women who were seronegative and DNA negative for the corresponding vaccine type at baseline ( month 0 ) and allowed inclusion of lesions with several oncogenic HPV types . This interim event-defined analysis was triggered when at least 23 cases of CIN2 + with HPV16 or HPV18 DNA in the lesion were detected in the total vaccinated cohort for efficacy . Analyses were done on a modified intention-to-treat basis . This trial is registered with the US National Institutes of Health clinical trial registry , number NCT00122681 . FINDINGS Mean length of follow-up for women in the primary analysis for efficacy at the time of the interim analysis was 14.8 ( SD 4.9 ) months . Two cases of CIN2 + associated with HPV16 or HPV18 DNA were seen in the HPV16/18 vaccine group ; 21 were recorded in the control group . Of the 23 cases , 14 ( two in the HPV16/18 vaccine group , 12 in the control group ) contained several oncogenic HPV types . Vaccine efficacy against CIN2 + containing HPV16/18 DNA was 90.4 % ( 97.9 % CI 53.4 - 99.3 ; p<0.0001 ) . No clinical ly meaningful differences were noted in safety outcomes between the study groups . INTERPRETATION The adjuvanted HPV16/18 vaccine showed prophylactic efficacy against CIN2 + associated with HPV16 or HPV18 and thus could be used for cervical cancer prevention Our objective was to determine the optimal duration of treatment with imiquimod for external genital warts over 4 , 8 , 12 or 16 weeks . A total of 120 women with a history of genital warts for a median of 3–6 months and prior alternative treatments in 73 % were evaluated for total clearance rates . There was no statistically significant difference in complete clearance rates after 16-week follow-up across treatment groups : four weeks ( 40.0 % ) , eight weeks ( 48.4 % ) , 12 weeks ( 39.3 % ) and 16 weeks ( 51.6 % ) . Imiquimod was well tolerated , and in those treated for four weeks there was a lower incidence of local skin reactions such as erythema and erosion , and no incidences of pain . These preliminary results suggest that a four-week treatment course of imiquimod applied thrice weekly for women with external genital warts may provide a reasonable approach with comparable efficacy and compliance , and minimal adverse events , drug costs and clinic visits The purpose of this r and omized , double-blind , placebo-controlled study was to determine the clinical efficacy and tolerability of an analog of imiquimod (2%)in cream to cure genital warts in women . Sixty preselected women , ranging between 18 and 45 years of age ( mean 24.3 ) and having 411 lesions ( mean 6.8 ) with clinical , histopathological and polymerase chain reaction ( PCR ) confirmed diagnosis of human papilloma virus ( HPV ) infection were r and omized to two parallel groups . Each patient received a precoded 40-g tube and instructions on how to apply the trial medication to their lesions at home two times daily for five consecutive days per week . The active treatment period was six weeks . Patients were evaluated on a weekly basis . A clinical ly and PCR established total clearance of target warts was recorded as a cure . By the end of the treatment , 43.3 % of patients and 42.8 % of warts were cured . Code disclosure revealed that imiquimod cream had cured 83.3 % of the treated patients and 84.3 % of the tested warts , while the placebo healed one subject and four warts ( p < 0.0001 ) . Eight patients ( 13.3 % ) in the imiquimod group experienced mild to moderate , non- objective , drug-induced symptoms with no dropouts . Among the 26 cured patients , five had a relapse after 11 months . In conclusion , the data presented demonstrate that 2 % imiquimod in cream with mild to moderate subjective side effects is significantly more effective than placebo in eliminating genital warts in women We describe a prospect i ve study design ed to assess the effectiveness of the commonly used clinic-based treatments for genital warts individually and in combination . Patients presenting with new or recurrent genital warts were r and omly allocated to one of five treatments on a weekly basis . The clinical endpoint was wart clearance or eight treatments , whichever occurred sooner . If there was not a good response by the eighth treatment , an alternate modality was offered . Four hundred and nine individuals were enrolled in the study . Almost no patients withdrew in any group due to adverse effects . Three-quarters of patients treated with podophyllin 25 % and cryotherapy concurrently required only two treatments to clear their warts . All had clearance in less than eight treatments . Single therapy with either trichloracetic acid or podophyllin 25 % result ed in longer time to wart clearance , and more persistent warts OBJECTIVES 1 ) To determinate the presence of human papillomavirus ( HPV ) in women with cervical condylomas after the trichloroacetic acid application by the polymerase chain reaction ( PCR ) test , and 2 ) to vali date the colposcopy test versus the PCR ( gold st and ard ) . PATIENTS AND METHODS A selected sample of 28 women of 18 to 45 years old with cervical condyloma acuminate , without evidence of cervical neoplasic lesion and with positive diagnosis of HPV with PCR was included . beta-globin gene was used as internal control and as DNA integrity marker . Women included in this study were divided in : treated group ( n = 14 ) , which were treated just one time with trichloroacetic acid to 90 % in the cervix , the cul de sacs and the vagina areas , and placebo group ( n = 14 ) , which were treated with physiological saline . After eight weeks of being applied the treatment , each one of the 28 women was HPV diagnosed again by colposcopy and PCR . RESULTS All women amplified for the beta-globin gene . In the treated group , 11/14 ( 78 % ) patients did not show amplification . The colposcopy showed two negative false , five positive false , one positive true and six negative true tests , revealing sensitivity of 33.33 % and specificity of 54.54 % . CONCLUSIONS From the molecular point of view , this study showed that the trichloroacetic acid application causes physical destruction of the infected tissue , without detecting DNA damage due to the cellular desquamation . On the other h and , the colposcopy regarding the PCR is not an appropriate test for the diagnosis and follow-up of the HPV infection Our objective was to assess the technical characteristics , side effects , complications , and effectiveness of electrosurgery vs continuous wave CO2 laser in the treatment of genital warts . This open clinical trial was made up of 208 evaluable patients ( 135 women and 73 men ) with vaginal and external anogenital condylomas . To avoid selection bias , in each patient half of the lesions measuring 2 cm2 or greater total linear area were treated with loop electroexcision and ball electrofulguration , and the other half were treated with CO2 laser excision and vaporization in a continuous wave mode spot welding . All patients were followed for at least 6 months ( maximum 18 months , mean 8 months ) after the last treatment received . The average operative time was 6 min for electrosurgery and 8 min for laser . Healing was completed in 95 % of patients with a lesional area of 5 cm2 or less and 100 % of patients with 5 cm2 or larger by the third and sixth postoperative week , respectively . Severe discomfort occurred in 12 % of patients , and 4 % of patients developed delayed complications , including vitiligo and scarring , irrespective of treatment modalities used . Complete clearance of warts in women and men after a single ( 51 % and 38 % ) and multiple ( 75 % and 64 % ) treatments were similar in areas treated with electrosurgery and CO2 laser . Electrosurgery appears to be as effective as continuous wave CO2 laser for treating vaginal and external anogenital condylomas , particularly those limited to a 5 cm2 or less area In a double-blind trial , 0.5 % podofilox ( podophyllotoxin ) or placebo was applied by patients to their own genital warts in up to four treatment cycles . At some time during the study , 25 of the 56 podofilox treated patients and none of the 53 placebo group were completely wart-free . At the end of the treatment , 73.6 % of the original warts in podofilox treated patients were gone compared with only 8.3 % of those in the placebo group ( mean percentage of total original wart area was reduced by 82.3 % compared with 4.2 % ) . 82 % of the treated warts in the podofilox group and 13 % in the placebo group had resolved at 6 weeks . Recurrence was observed in 34 % of the previously resolved warts . Consistent with this rate of recurrence , new warts developed in a third of the subjects in each group at sites remote from the treatment site . There were no systemic adverse reactions , although transient inflammation , erosion , pain , and burning were common Department of Obstetrics and Gynecology , The Uni ersity of Tennessee Medical Center at Knox ille , Knox ille , TN , USA Department of Pathology , Jewish General Hospital , , Quebec , Montreal , Canada Department of Medicine , Indiana Uni ersity School of Medicine , Indianapolis , IN , USA Department of Microbiology and Immunology , Indiana Uni ersity School of Medicine , Indianapolis , IN , USA Department of Pathology , Indiana Uni ersity School of Medicine , Indianapolis , IN , The cost effectiveness of 25 % podophyllin resin and 0.5 % podophyllotoxin solution in the treatment of genital warts in Genitourinary Medicine Clinic attenders was studied . Although the average treatment cost for a course of podophyllotoxin was more than that for podophyllin resin ( £ 20.75 v. £ 14.95 respectively ) the overall cure rate with podophyllotoxin was 66 % as opposed to 34.6 % with podophyllin . When the costing of secondary treatment options was considered the cost per patient cured of warts with podophyllin resin was £ 27.15 compared with £ 25.73 for podophyllotoxin solution ( not significant ) AIM The aims of this study were to : 1 ) ascertain if podophyllin resin in 0.5 % [ PE(0.5 % ) ] and 0.25 % [ PE(0.25 % ) ] in ethanol ( PE ) self-applied sequentially for 3 days with 4 days break cycle is as effective as supervised podophyllin 25 % in tincture benzoin ( PB ) applied in the clinic biweekly in treating penile warts and 2 ) ascertain if PE causes less skin irritation than PB . METHODS AND RESULTS The clearance rate of penile warts was 36.4 % ( 4/11 ) in PE ( 0.5 % ) treated group , 66.7 % ( 4/6 ) in the PE ( 0.25 % ) treated group and 33.3 % ( 6/18 ) for PB treated group after 1 week ( ns ) . The wart clearance rate at 6 weeks for PE ( 0.5 % ) treated group , PE ( 0.25 % ) treated group and PB treated group were 81.8 % ( 9/11 ) , 100 % ( 6/6 ) and 83.3 % ( 15/17 ) respectively ( ns ) . There were 47 individual warts on the penis of the 17 patients in the PE treated group and 58 individual warts on the penis of the 18 patients in the PB treated group . Based on the response of individual warts to the 2 treatment regimens , the clearance rate was 42.6 % ( 20/47 ) for the PE treated group and 25 % ( 15/56 ) for the PB treated group after 1 week treatment ( ns ) . At 6 weeks follow-up , the clearance rate for the PE treated group and the PB treated group were 85.1 % ( 40/47 ) and 73.2 % ( 41/56 ) respectively ( ns ) . Skin irritation including superficial erosions , pain and itch were observed in 47 % ( 8/17 ) in patients treated with PE compared to 38.9 % ( 7/18 ) in patients treated with PB ( ns ) during the 6 weeks follow-up period . The clearance rate of patients treated with PE ( 0.25 % ) was compared to those treated with PE ( 0.5 % ) . Four out of six of PE ( 0.25 % ) treated patients had clearance of warts after 1 week and 100 % clearance at the end of 6 weeks . None experienced any skin irritation . CONCLUSION This study demonstrates that 0.5 % podophyllin ( and possibly 0.25 % podophyllin ) in ethanol is effective in eradicating penile warts . It can be used by patients for self-treatment at home with greater convenience and is more cost effective than the conventional podophyllin 25 % in tincture benzoin paint OBJECTIVE The purpose of this double-blind , placebo-controlled study was to evaluate the safety , clinical efficacy and tolerability of imiquimod ( 2 % ) in cream to cure external genital warts in males . METHODS Preselected male patients ( n=60 ) ranging between 18 and 50 years of age ( mean 24.2 ) harbouring 558 lesions ( mean 9.3 ) with clinical , histopathological and polymerase chain reaction ( PCR ) confirmed diagnosis of human papilloma virus ( HPV ) infection were r and omized to two parallel groups . Each patient was allocated a precoded 25 g tube , and instructions on how to apply the trial medication to their lesions at home once daily for three consecutive days per week ( max . 12 application in 4 weeks ) . To evaluate the safety , clinical efficacy and tolerance , patients were exa-mined on a weekly basis . Cure was defined as the total elimination of treated warts with PCR , and Southern blot hybridization confirmed negative HPV DNA . RESULTS By the end of the treatment , 40 % ( 24/60 ) patients and 49.8 % ( 278/558 ) warts were cured . Breaking the code revealed that imiquimod cream had cured 70 % ( 21/30 ) patients and 86.8 % of warts , while placebo healed three subjects and 28 warts ( P=0.0001 ) . Eleven patients ( 18.3 % ) , predominantly in the imiquimod cream group , experienced mild to moderate , non- objective , drug-related side effects with no dropouts . The study was followed up for 18 months from the first day of the treatment , and among the 26 cured patients , one in the imiquimod cream group and two in the placebo had a relapse after 14 months . CONCLUSION The study demonstrated that 2 % imiquimod in cream with mild non- objective side effects is safe , tolerable and significantly more effective than placebo in curing external genital warts in males Background : The burden of anogenital warts will be a determining factor when making decisions about the type of human papillomavirus ( HPV ) vaccine to be used ( bivalent or quadrivalent ) and whether to vaccinate males . We conducted a multicenter prospect i ve study to ( 1 ) describe the impact of anogenital warts on quality of life and ( 2 ) estimate the quality -adjusted life-years ( QALYs ) lost due to anogenital warts . Methods : Between September 2006 and February 2008 , 272 patients with a first or recurrent episode of anogenital warts were recruited from the clinical practice s of 42 physicians across Canada . Quality of life was measured at recruitment , and 2 and 6 months later with the EuroQol , Short Form-12 , short Spielberg State-Trait Anxiety Inventory , and HPV impact profile . The duration of an episode and QALYs lost due to anogenital warts were estimated among 51 incident cases recruited within 90 days of disease onset . Results : Anogenital warts had a significant impact on the quality of life . This negative impact was similar for first and recurrent episodes , and lasted as long as lesions persisted . Anogenital warts had the greatest negative impact on usual activities , pain/discomfort , and anxiety/depression , and on self-image , sexual activity , and partner issues and possible transmission . The median duration of a first anogenital wart episode amongst incident cases was 125 days and result ed in QALYs lost of 0.017 to 0.041 , which is equivalent to 6 to 15 days of healthy life lost . Conclusions : The burden of anogenital warts is substantial and should be considered by physicians and public health officials when making recommendations about HPV vaccination In an observer blind comparative study , 130 men with penile warts were r and omly allocated to treatment with either cryotherapy or trichloroacetic acid ( TCAA ) . There was no significant difference in response to treatment , side effects , or recurrence rates between the two treatments . Warts resolved in 81 % of patients treated with TCAA compared with 88 % of those treated with cryotherapy . Early recurrence occurred in 36 % of patients treated with TCAA and in 39 % of those treated with cryotherapy ABSTRACT Genital human papillomavirus infection is one of the most common sexually transmitted diseases . Imiquimod is a new agent , an immune-response modifier , that has been demonstrated to have potent in vivo antiviral and antitumor effects in animal models . The present prospect i ve , multicenter , double-blind , r and omized , vehicle-controlled trial evaluated the efficacy and safety of daily patient-applied imiquimod for up to 16 weeks for the treatment of external genital warts . Wart recurrence was investigated during a 12-week treatment-free follow-up period . In the intent-to-treat analysis , baseline warts cleared from 49 of 94 ( 52 % ) patients treated with 5 % imiquimod cream , 13 of 90 ( 14 % ) patients treated with 1 % imiquimod cream , and 3 of 95 ( 4 % ) vehicle-treated patients ; the differences between the groups treated with vehicle and imiquimod were significant ( P < 0.0001 ) . For subjects who completed the follow-up period , recurrence rates after a complete response were 19 % ( 9 of 48 patients ) in the 5 % imiquimod cream group , 17 % ( 2 of 12 ) in the 1 % imiquimod cream group , and 0 % ( 0 of 3 ) in the vehicle-treated group . There were no systemic reactions , although local skin reactions ( generally of mild or moderate severity ) were common , particularly in the 5 % imiquimod cream group . Local reactions caused two patients to discontinue treatment . The most frequently reported local skin reactions were erythema , excoriation or flaking , and erosion . Patient-applied 5 % imiquimod cream is effective for the treatment of external genital warts and has a favorable safety profile In this prospect i ve study , three groups of patients were enrolled : group 1 , patients with high grade squamous intraepithelial lesions ( CIN 2 and 3 ) and carcinoma in situ ( n = 56 ) ; group 2 , patients with benign vulvar and perineal human papillomavirus lesions ( n = 83 ) ; and group 3 , patients with disseminated foci of penile shaft condylomatous lesions ( n = 65 ) . Each of the groups was r and omly equally divided into two subgroups . One subgroup was treated with a laser beam with an output of 60 W and a spot size of 1 - 1.5 mm , creating high power density ( HPD ) ranging between 3,4000 and 7,640 W/cm2 , while the other was treated with low power density ( LPD ) with an output of 20 W and the same spot sizes , creating an LPD ranging between 1,136 and 2,547 W/cm2 . In group 1 , the time to complete treatment was shorter using the HPD technique ( P < .0003 ) , and more satisfactory histologic edges were available ( P < .007 ) . HPD was also associated with a significantly shorter healing time and improved cosmetic results in groups 2 and 3 ( P = .001 ) . No difference was found in the time to complete therapy or the occurrence of infection when the different modalities were compared . The results of this study suggest that for specific disease entities , HPD is associated with better treatment outcomes than is LPD R and omized clinical trials are currently examining the efficacy of a nonavalent human papillomavirus ( HPV ) vaccine , including HPV-types 6/11/16/18/31/33/45/52/58 . Evidence on the cost-effectiveness of the nonavalent is required for timely policy-decisions . We compared the potential cost-effectiveness of the nonavalent and quadrivalent HPV vaccines . We used a multi-type individual-based transmission-dynamic model of HPV infection and diseases , 70-year time-horizon , 3 % discount rate and healthcare payer perspective . We calibrated the model to Canadian sexual behavior and epidemiologic data , and estimated Quality -Adjusted Life-Years ( QALYs ) lost and costs ( $ CAN 2010 ) from the literature . Under base-case assumptions ( vaccinating 10-year-old girls , 80 % coverage , 95$/dose , vaccine-type efficacy = 95 % , cross-protection for the quadrivalent vaccine , duration of vaccine-type protection ( cross-protection ) = 20 ( 10 ) years ) , using the quadrivalent and nonavalent vaccines is estimated to cost $ 15,528 [ 12,056 ; 19,140 ] and $ 12,203 [ 9,331 ; 17,292 ] per QALY-gained , respectively . At equal price , the nonavalent vaccine is more cost-effective than the quadrivalent vaccine , even when assuming both shorter duration of protection ( nonavalent = 20 years vs. quadrivalent = lifelong ) and lower vaccine-type efficacy ( nonavalent = 85 % vs. quadrivalent = 95 % ) . However , the additional cost per dose of the nonavalent vaccine should not exceed $ 11 to remain more cost-effective than the quadrivalent vaccine , and $ 24 to represent a cost-effective alternative to the quadrivalent vaccine ( using a $ 40,000/QALY-gained threshold ) . The nonavalent vaccine can be a cost-effective alternative to the quadrivalent vaccine , even in scenarios where nonavalent vaccine efficacy is 85 % . However , because most cervical cancers are caused by HPV-16/18 , it is unlikely that the nonavalent would be used if its efficacy against these types is lower than current HPV vaccines Objectives : To compare the efficacy and safety of combination therapy with cryotherapy and podophyllotoxin 0.15 % cream versus cryotherapy alone in the treatment of anogenital warts . Methods : A r and omised , double-blind , multicentre controlled trial . Patients received podophyllotoxin cream or placebo twice daily for 3 days/week for up to 4 weeks , with weekly cryotherapy continued to week 12 if required . Further treatment from week 12 to 24 was discretionary . Patients were stratified by sex and history of warts . HIV positivity , warts treated in the past 4 months , or warts with a combined area of less than 10 mm2 were exclusion criteria . Primary endpoints were clearance at weeks 4 and 12 . Results : 70 patients per group were r and omly assigned and started treatment ; 101 first-episode warts , 91 male . No treatment-related serious adverse events were reported . Follow-up at week 12 was 85 % . By intention-to-treat analysis , clearances at 4 and 12 weeks were higher in the combination group ( 60.0 % and 60.0 % , respectively ) than with cryotherapy alone ( 45.7 % , 45.7 % ) although not statistically significant ( RR 1.31 , 95 % CI 0.95to 1.81 ) . By week 24 there was no difference between the groups ( 68.6 % and 64.3 % , respectively ; RR 1.07 , CI 0.84 to 1.35 ) . At week 4 , wart clearance was higher in men ( p = 0.001 ) and those with a past history of warts ( p = 0.009 ) , but these differences were not detected at week 12 . There was some evidence for a higher relapse rate in the group receiving cryotherapy alone . Conclusions : Initial combination therapy with podophyllotoxin/cryotherapy was well tolerated and may have result ed in earlier clearance in some patients , compared with cryotherapy alone ; however , overall differences in clearance rates were not statistically significant OBJECTIVE --To compare the efficacy of 0.50 % and 0.25 % podophyllotoxin preparations against previously untreated penile warts . DESIGN --The study was performed as a double-blind , placebo-controlled investigation on 57 males r and omly allocated to one of three groups of 19 males in each , receiving either the placebo solution ( 70 % ethanolic vehicle ) or one of the two podophyllotoxin preparations for 1 - 2 self-treatment courses b.i.d . for three days , separated by a one-week drug-free interval . SETTING --The STD out-patient clinic of the Department of Dermatovenereology at Southern Hospital of Stockholm , Sweden . RESULT --The placebo solution merely exerted a marginal influence on the warts while a primary cure was documented in 72 % ( 13/18 ) and 81 % ( 13/16 ) of altogether 34 evaluable men who treated their warts with 0.25 % and 0.50 % podophyllotoxin , respectively . Follow-up investigation ( range 5 - 23 weeks ) was possible for 24 of 26 podophyllotoxin treated men who were primarily cured . Some degree of relapse occurred in nine of them ( 38 % ) . Of these relapses , warts occurred on previously untreated sites only in three cases ( 33 % ) , and in another four ( 44 % ) relapse was associated with regrowth on treated sites as well as on new sites . When analysing the debulking potential of podophyllotoxin , it appeared that 0.25 % podophyllotoxin eradicated 184 of originally 217 warts ( 85 % ) ; the corresponding figure for 0.50 % podophyllotoxin was as high as 130 of 135 lesions ( 96 % ) . Side effects were generally mild-moderate and well tolerated . CONCLUSION --The results underscore the potential usefulness of low-dose podophyllotoxin preparations as first-line chemotherapy of condylomata acuminata for home-treatment . The efficacy from topical use of 0.25 % podophyllotoxin detected in the study is certainly of a magnitude signifying that podophyllotoxin concentrations lower than 0.50 % deserve further investigation if the drug may be incorporated into alternative vehicles such as creams or ointments 60 patients with first-episode perianal condylomata acuminata were r and omly assigned to podophyllin application or surgical excision . 58 % of the male patients were homosexual and 33 % of the female patients regularly had anal intercourse . Podophyllin completely cleared warts from 23 of 30 ( 76.6 % ) patients compared with 28 of 30 ( 93.3 % ) for surgical excision . After wart clearance the cumulative recurrence rates were 18 % for surgical excision and 43 % for podophyllin at 3 months ( p less than 0.05 ) , 22 % and 56 % at 6 months ( p less than 0.01 ) , 26 % and 56 % at 9 months ( p less than 0.01 ) , and 29 % and 65 % at 12 months ( p less than 0.01 ) . All patients were treated as out patients and all surgical procedures were carried out under local anaesthesia . Both regimens were well tolerated Patient-applied formulations of 0.5 % podofilox ( podophyllotoxin ) were evaluated for the treatment of external genital warts in a double-blind , placebo-controlled study . Seventytwo women were enrolled and , using a r and omized , computer-generated list , assigned to receive either active drug or placebo in a 2:1 ratio . Patients were instructed to apply the medication to their external warts twice each day for 3 consecutive days , followed by 4 days without treatment . This cycle was repeated at weekly intervals for a maximum of 4 weeks ( and a minimum of 2 weeks ) . Patients were evaluated weekly for the first month and then at weeks 6 and 10 . The number of warts present was recorded and the overall improvement was assessed . The treated area was examined , the patients were question ed about any adverse effects , and st and ard hematologic/biochemical studies were conducted . The final results showed that podofilox cleared 74 % of the total wart count , compared with an 18 % regression in the placebo group ( P<.001 ) . The investigators ' assessment s of improvement correctly distinguished active drug from placebo at every observation point . Local untoward effects were minor and transient . There was no evidence of systemic effects . It is concluded that patientapplied podofilox is a safe and effective therapy for genital condylomata in women . When available , this drug will simplify the treatment of genital warts by providing a patient-applied alternative therapy Imiquimod , an immune response modifier , has been demonstrated to be safe and effective in the treatment of external genital and perianal warts caused by human papillomavirus ( HPV ) . To identify the molecular mechanism(s ) by which condylomata acuminata clear during topical treatment with imiquimod , wart skin biopsies were taken from patients before treatment , at treatment week 6 , and at the end of treatment . Tissues were analyzed for HPV DNA and for mRNA of several cytokines and HPV gene products . Wart clearance was associated with evidence of tissue production of interferon-alpha , -beta , and -gamma and tumor necrosis factor-alpha . Regression of warts was strongly associated with a decrease in HPV DNA and in mRNA expression for both early and late viral proteins . Thus , topical imiquimod treatment of anogenital warts led to significant increases in local production of multiple interferon mRNAs and a significant reduction in virus load as measured by decreases in HPV DNA and mRNA for early HPV proteins OBJECTIVE To evaluate the effectiveness of sleeve circumcision of prepuce and coronary sulcus skin in the treatment of patients with multiple condyloma acuminatum ( CA ) of coronary sulcus of penis . METHODS In a r and omized clinical control study , 35 patients were r and omized to the treatment group and received sleeve circumcision of prepuce and coronary sulcus skin . 34 patients were r and omized to the control group , received electric cauterization of verrucae plus the general circumcision . The recurrence of CA was evaluated in follow-up visit within three months after the treatment . RESULTS The stitches were taken out 10.2 days after operation in the treatment group , and 8.1 days in the control group . There were no complication in the treatment group , the average healing time of electric cauterization wound was 19.4 days in the control group . There was a statistically significant difference in the recurrence rate of CA between the treatment group and the control group ( 5.7 % vs 26.5 % , P < 0.05 ) . CONCLUSIONS The sleeve circumcision of prepuce and coronary sulcus skin is more effective than electric cauterization of verrucae plus the general circumcision in the treatment of patients with multiple condyloma acuminatum of coronary sulcus of penis Background : Anogenital warts are a common sexually transmitted disease caused by human papillomaviruses . Despite the fact , that imiquimod and podophyllotoxin represent common topical agents , direct comparative studies lack . This work compares the effectiveness and safety of self-applied imiquimod 5 % cream and podophyllotoxin 0.5 % solution . Methods : Within 2 years , consecutive patients presenting with untreated anogenital warts were included in a r and omized , open label trial . The primary endpoint was complete clearance at the end of treatment ( 4 weeks after the start with podophyllotoxin , 16 weeks after the start of imiquimod therapy ) . Side effects were evaluated as a secondary endpoint . Results : A total of 45 patients , 7 women and 35 men , of whom 5 were circumcised , concluded the treatment and were eligible for evaluation . The rates of clearance of baseline warts among treatment groups were 72 % ( 95 % confidence interval [ CI ] , 52%–86 % ) in the podophyllotoxin group and 75 % ( 95 % CI , 53%–98 % ) in the imiquimod group . Statistically , clearance rates were identical ( P = 1 ) . The differences in side effects between treatment groups were statistically not significant ( P = 0.24 ) . Conclusions : The current study , a direct comparison of both , confirms the previously obtained mathematical data , that imiquimod 5 % cream and podophyllotoxin 0.5 % solution have an identical beneficial effect on anogenital warts and are associated with identical and acceptable side effects . Both substances constitute effective and safe treatments of untreated anogenital warts in immunocompetent individuals BACKGROUND Human papillomavirus (HPV)-6/11/16/18 vaccine reduces the risk of HPV-6/11/16/18-related cervical intraepithelial neoplasia ( CIN ) 1 - 3 or adenocarcinoma in situ ( AIS ) . Here , its impact on CIN1 - 3/AIS associated with nonvaccine oncogenic HPV types was evaluated . METHODS We enrolled 17,622 women aged 16 - 26 years . All underwent cervicovaginal sampling and Pap testing at regular intervals for up to 4 years . HPV genotyping was performed for biopsy sample s , and histological diagnoses were determined by a pathology panel . Analyses were conducted among subjects who were negative for 14 HPV types on day 1 . Prespecified analyses included infection of 6 months ' duration and CIN1 - 3/AIS due to the 2 and 5 most common HPV types in cervical cancer after HPV types 16 and 18 , as well as all tested nonvaccine types . RESULTS Vaccination reduced the incidence of HPV-31/45 infection by 40.3 % ( 95 % confidence interval [ CI ] , 13.9 % to 59.0 % ) and of CIN1 - 3/AIS by 43.6 % ( 95 % CI , 12.9 % to 64.1 % ) , respectively . The reduction in HPV-31/33/45/52/58 infection and CIN1 - 3/AIS was 25.0 % ( 95 % CI , 5.0 % to 40.9 % ) and 29.2 % ( 95 % CI , 8.3 % to 45.5 % ) , respectively . Efficacy for CIN2 - 3/AIS associated with the 10 nonvaccine HPV types was 32.5 % ( 95 % CI , 6.0 % to 51.9 % ) . Reductions were most notable for HPV-31 . CONCLUSIONS HPV-6/11/16/18 vaccine reduced the risk of CIN2 - 3/AIS associated with nonvaccine types responsible for approximately 20 % of cervical cancers . The clinical benefit of cross-protection is not expected to be fully additive to the efficacy already observed against HPV-6/11/16/18-related disease , because women may have > 1 CIN lesion , each associated with a different HPV type . TRIAL REGISTRATION Clinical Trials.gov identifiers : NCT00092521 , NCT00092534 , and NCT00092482 |
13,870 | 30,995,309 | RESULTS The results showed that the degree of processing influences the health effects of fruit-based products .
Fresh and dried fruits appeared to have a neutral or protective effect on health , 100 % fruit juices had intermediary effects , and high consumption of canned fruit and sweetened fruit juice was positively associated with the risk of all-cause mortality and type 2 diabetes , respectively . | CONTEXT The degree of fruit processing is rarely considered in epidemiological studies of fruit consumption .
OBJECTIVE Pooled analyses and meta-analyses of cohort studies and r and omized controlled trials that linked fruit consumption with the risk of chronic disease and metabolic deregulation were review ed systematic ally to examine the effects of fruit processing . | Because fruits and vegetables are rich in bioactive compounds with potential cancer-preventive actions , increased consumption may reduce the risk of ovarian cancer . Evidence on the association between fruit and vegetable intake and ovarian cancer risk has not been consistent . We analyzed and pooled the primary data from 12 prospect i ve studies in North America and Europe . Fruit and vegetable intake was measured at baseline in each study using a vali date d food-frequency question naire . To summarize the association between fruit and vegetable intake and ovarian cancer , study -specific relative risks ( RR ) were estimated using the Cox proportional hazards model , and then combined using a r and om-effects model . Among 560,441 women , 2,130 cases of invasive epithelial ovarian cancer occurred during a maximum follow-up of 7 to 22 years across studies . Total fruit intake was not associated with ovarian cancer risk — the pooled multivariate RR for the highest versus the lowest quartile of intake was 1.06 [ 95 % confidence interval ( 95 % CI ) , 0.92 - 1.21 ; P value , test for trend = 0.73 ; P value , test for between- studies heterogeneity = 0.74 ] . Similarly , results for total vegetable intake indicated no significant association ( pooled multivariate RR , 0.90 ; 95 % CI , 0.78 - 1.04 , for the highest versus the lowest quartile ; P value , test for trend = 0.06 ; P value , test for between- studies heterogeneity = 0.31 ) . Intakes of botanically defined fruit and vegetable groups and individual fruits and vegetables were also not associated with ovarian cancer risk . Associations for total fruits and vegetables were similar for different histologic types . These results suggest that fruit and vegetable consumption in adulthood has no important association with the risk of ovarian cancer Background A series of recent reports from large-scale cohort studies involving more than 100,000 subjects reported no or only very small inverse associations between fruit and vegetable intake and overall cancer incidence , despite having sufficient power to do so . To date , however , no such data have been reported for Asian population s. Objective To provide some indication of the net impact of fruit and vegetable consumption on overall cancer prevention , we examined these associations in a pooled analysis of large-scale cohort studies in Japanese population s. Methods We analyzed original data from four cohort studies that measured fruit and vegetable consumption using vali date d question naires at baseline . Hazard ratios ( HRs ) in the individual studies were calculated , with adjustment for a common set of variables , and combined using a r and om-effects model . Results During 2,318,927 person-years of follow-up for a total of 191,519 subjects , 17,681 cases of overall cancers were identified . Consumption of fruit or vegetables was not associated with decreased risk of overall cancers : corresponding HRs for the highest versus lowest quartiles of intake for men and women were 1.03 ( 95 % CI , 0.97–1.10 ; trend p = 1.00 ) and 1.03 ( 95 % CI , 0.95–1.11 ; trend p = 0.97 ) , respectively , for fruit and 1.07 ( 95 % CI , 1.01–1.14 ; trend p = 0.18 ) and 0.98 ( 95 % CI , 0.91–1.06 ; trend p = 0.99 ) , respectively , for vegetables , even in analyses stratified by smoking status and alcohol drinking . Conclusions The results of this pooled analysis do not support inverse associations of fruit and vegetable consumption with overall cancers in the Japanese population Abstract Objective To assess the prospect i ve associations between consumption of ultra-processed food and risk of cancer . Design Population based cohort study . Setting and participants 104 980 participants aged at least 18 years ( median age 42.8 years ) from the French NutriNet-Santé cohort ( 2009 - 17 ) . Dietary intakes were collected using repeated 24 hour dietary records , design ed to register participants ’ usual consumption for 3300 different food items . These were categorised according to their degree of processing by the NOVA classification . Main outcome measures Associations between ultra-processed food intake and risk of overall , breast , prostate , and colorectal cancer assessed by multivariable Cox proportional hazard models adjusted for known risk factors . Results Ultra-processed food intake was associated with higher overall cancer risk ( n=2228 cases ; hazard ratio for a 10 % increment in the proportion of ultra-processed food in the diet 1.12 ( 95 % confidence interval 1.06 to 1.18 ) ; P for trend<0.001 ) and breast cancer risk ( n=739 cases ; hazard ratio 1.11 ( 1.02 to 1.22 ) ; P for trend=0.02 ) . These results remained statistically significant after adjustment for several markers of the nutritional quality of the diet ( lipid , sodium , and carbohydrate intakes and /or a Western pattern derived by principal component analysis ) . Conclusions In this large prospect i ve study , a 10 % increase in the proportion of ultra-processed foods in the diet was associated with a significant increase of greater than 10 % in risks of overall and breast cancer . Further studies are needed to better underst and the relative effect of the various dimensions of processing ( nutritional composition , food additives , contact material s , and neoformed contaminants ) in these associations . Study registration Clinical trials.gov NCT03335644 OBJECTIVE Assumptions have linked orange juice ( OJ ) consumption with weight gain and adverse effects on health due to its sugar content ; however , epidemiologic studies have not shown increased risk for overweight or obesity with the consumption of 100 % OJ . The aim of this study was to verify whether the combination of a reduced-calorie diet ( RCD ) and 100 % OJ contribute to weight loss , promote changes in glucose and lipid metabolism , and improve diet quality in obese individuals . METHODS A r and omized controlled trial with 78 obese patients ( age 36 ± 1 y , body mass index [ BMI ] 33 ± 3 kg/m2 ) were enrolled in two groups : Individuals in the OJ group su bmi tted to an RCD that included OJ ( 500 mL/d ) , and individuals in the control group su bmi tted to an RCD without OJ . Body composition , biochemical biomarkers , and dietary intake were analyzed over a 12-wk period . RESULTS Both treatments had similar outcomes regarding body weight ( -6.5 kg ; P = 0.363 ) , BMI ( -2.5 kg/m2 ; P = 0.34 ) , lean mass ( -1 kg ; P = 0.29 ) , fat mass ( -5 kg ; P = 0.58 ) , body fat ( -3 % ; P = 0.15 ) , and waist-to-hip ratio ( -0.1 ; P = 0.79 ) . Insulin levels in the OJ group decreased by 18 % ( P = 0.05 ) , homeostasis model assessment -insulin resistance by 33 % ( P = 0.04 ) , total cholesterol by 24 % ( P = 0.004 ) , low-density lipoprotein cholesterol by 24 % ( P ≤ 0.001 ) , and high-sensitivity C-reactive protein levels by 33 % ( P = 0.001 ) compared with the control group . Consumption of energy and nutrients was similar between the two groups , but vitamin C and folate increased by 62 % ( P ≤ 0.015 ) and 39 % ( P = 0.033 ) , respectively , after OJ intervention . CONCLUSION When consumed concomitantly with an RCD , OJ does not inhibit weight loss ; ameliorate the insulin sensitivity , lipid profile , or inflammatory status , or contribute nutritionally to the quality of the diet The association between drinking 100 % fruit juice and long-term weight gain is controversial and has been investigated in few studies . We examined whether 100 % fruit juice consumption was associated with weight change in a large prospect i ve cohort of postmenopausal women . We analyzed data from 49,106 postmenopausal women in the United States enrolled in the Women 's Health Initiative between 1993 and 1998 . Food frequency question naires at baseline and year 3 assessed food and beverage intake . Body weight was measured at in-person clinic visits . We used linear mixed effects modeling to determine the association between change in 100 % fruit juice consumption and 3-year weight change over the same time period . Covariates of interest included age , demographic factors , smoking , body mass index , hormone replacement therapy , lifestyle factors , change in whole fruit intake , and change in sugar-sweetened beverage intake . The mean weight change was 3.2 lbs . over 3 years . In multivariable adjusted analyses , each 1 serving/day increase in 100 % fruit juice intake was associated with a 3-year weight gain of 0.39 lbs . ( 95 % confidence interval : 0.10 , 0.69 ) . In conclusion , an increase in 100 % fruit juice consumption was associated with a small amount of long-term weight gain in postmenopausal women The importance of vegetable and fruit intakes for the prevention of fracture in older women is not well understood . Few studies have explored vegetable and fruit intakes separately , or the associations of specific types of vegetables and fruits with fracture hospitalisations . The objective of this study was to examine the associations of vegetable and fruit intakes , separately , and specific types of vegetables and fruits with fracture-related hospitalisations in a prospect i ve cohort of women aged ≥70 years . Vegetable and fruit intakes were assessed at baseline ( 1998 ) in 1468 women using a food frequency question naire . The incidence of fracture-related hospitalisations over 14.5 years of follow-up was determined using the Hospital Morbidity Data Collection , linked via the Western Australian Data Linkage System . Fractures were identified in 415 ( 28.3 % ) women , of which 158 ( 10.8 % ) were hip fractures . Higher intakes of vegetables , but not fruits , were associated with lower fracture incidence . In multivariable-adjusted models for vegetable types , cruciferous and allium vegetables were inversely associated with all fractures , with a hazard ratio ( HR ) ( 95 % confidence interval ) of 0.72 ( 0.54 , 0.95 ) and 0.66 ( 0.49 , 0.88 ) , respectively , for the highest vs. lowest quartiles . Increasing vegetable intake , with an emphasis on cruciferous and allium vegetables , may prevent fractures in older postmenopausal women Dietary recommendations to promote health include fresh , frozen and tinned fruit , but few studies have examined the health benefits of tinned fruit . We therefore studied the association between tinned fruit consumption and mortality . We followed up participants from three prospect i ve cohorts in the United Kingdom : 22,421 participants from the European Prospect i ve Investigation into Cancer and Nutrition (EPIC)-Norfolk cohort ( 1993–2012 ) , 52,625 participants from the EPIC-Oxford cohort ( 1993–2012 ) , and 7440 participants from the Whitehall II cohort ( 1991–2012 ) , all reporting no history of heart attack , stroke , or cancer when entering these studies . We estimated the association between frequency of tinned fruit consumption and all cause mortality ( primary outcome measure ) using Cox regression models within each cohort , and pooled hazard ratios across cohorts using r and om-effects meta- analysis . Tinned fruit consumption was assessed with vali date d food frequency question naires including specific questions about tinned fruit . During 1,305,330 person years of follow-up , 8857 deaths occurred . After adjustment for lifestyle factors and risk markers the pooled hazard ratios ( 95 % confidence interval ) of all cause mortality compared with the reference group of tinned fruit consumption less often than one serving per month were : 1.05 ( 0.99 , 1.12 ) for one to three servings per month , 1.10 ( 1.03 , 1.18 ) for one serving per week , and 1.13 ( 1.04 , 1.23 ) for two or more servings per week . Analysis of cause-specific mortality showed that tinned fruit consumption was associated with mortality from cardiovascular causes and from non-cardiovascular , non-cancer causes . In a pooled analysis of three prospect i ve cohorts from the United Kingdom self-reported tinned fruit consumption in the 1990s was weakly but positively associated with mortality during long-term follow-up . These findings raise questions about the evidence underlying dietary recommendations to promote tinned fruit consumption as part of a healthy diet 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 OBJECTIVE : To examine the long-term relationship between changes in water and beverage intake and weight change . SUBJECTS : Prospect i ve cohort studies of 50 013 women aged 40–64 years in the Nurses ’ Health Study ( NHS , 1986–2006 ) , 52 987 women aged 27–44 years in the NHS II ( 1991–2007 ) and 21 988 men aged 40–64 years in the Health Professionals Follow-up Study ( 1986–2006 ) without obesity and chronic diseases at baseline . MEASURES : We assessed the association of weight change within each 4-year interval , with changes in beverage intakes and other lifestyle behaviors during the same period . Multivariate linear regression with robust variance and accounting for within-person repeated measures were used to evaluate the association . Results across the three cohorts were pooled by an inverse-variance-weighted meta- analysis . RESULTS : Participants gained an average of 1.45 kg ( 5th to 95th percentile : −1.87 to 5.46 ) within each 4-year period . After controlling for age , baseline body mass index and changes in other lifestyle behaviors ( diet , smoking habits , exercise , alcohol , sleep duration , TV watching ) , each 1 cup per day increment of water intake was inversely associated with weight gain within each 4-year period ( −0.13 kg ; 95 % confidence interval ( CI ) : −0.17 to −0.08 ) . The associations for other beverages were : sugar-sweetened beverages ( SSBs ) ( 0.36 kg ; 95 % CI : 0.24–0.48 ) , fruit juice ( 0.22 kg ; 95 % CI : 0.15–0.28 ) , coffee ( −0.14 kg ; 95 % CI : −0.19 to −0.09 ) , tea ( −0.03 kg ; 95 % CI : −0.05 to −0.01 ) , diet beverages ( −0.10 kg ; 95 % CI : −0.14 to −0.06 ) , low-fat milk ( 0.02 kg ; 95 % CI : −0.04 to 0.09 ) and whole milk ( 0.02 kg ; 95 % CI : −0.06 to 0.10 ) . We estimated that replacement of 1 serving per day of SSBs by 1 cup per day of water was associated with 0.49 kg ( 95 % CI : 0.32–0.65 ) less weight gain over each 4-year period , and the replacement estimate of fruit juices by water was 0.35 kg ( 95 % CI : 0.23–0.46 ) . Substitution of SSBs or fruit juices by other beverages ( coffee , tea , diet beverages , low-fat and whole milk ) were all significantly and inversely associated with weight gain . CONCLUSION : Our results suggest that increasing water intake in place of SSBs or fruit juices is associated with lower long-term weight gain OBJECTIVE : To examine the changes in intake of fruits and vegetables in relation to risk of obesity and weight gain among middle-aged women . DESIGN : Prospect i ve cohort study with 12 y of follow-up conducted in the Nurses ' Health Study .SUBJECTS : A total of 74 063 female nurses aged 38–63 y , who were free of cardiovascular disease , cancer , and diabetes at baseline in 1984 . MEASUREMENTS : Dietary information was collected using a vali date d food frequency question naire , and body weight and height were self-reported . RESULTS : During the 12-y follow-up , participants tended to gain weight with aging , but those with the largest increase in fruit and vegetable intake had a 24 % of lower risk of becoming obese ( BMI ≥30 kg/m2 ) compared with those who had the largest decrease in intake after adjustment for age , physical activity , smoking , total energy intake , and other lifestyle variables ( relative risk ( RR ) , 0.76 ; 95 % confidence interval ( CI ) , 0.69–0.86 ; P for trend < 0.0001 ) . For major weight gain ( ≥25 kg ) , women with the largest increase in intake of fruits and vegetables had a 28 % lower risk compared to those in the other extreme group ( RR , 0.72 ; 95 % CI , 0.55–0.93 ; P=0.01 ) . Similar results were observed for changes in intake of fruits and vegetables when analyzed separately . CONCLUSIONS : Our findings suggest that increasing intake of fruits and vegetables may reduce long-term risk of obesity and weight gain among middle-aged women Several dietary factors have been studied in relation to prostate cancer ; however , most studies have not reported on subtypes of fruit and vegetables or tumor characteristics , and results obtained so far are inconclusive . This study aim ed to examine the prospect i ve association of total and subtypes of fruit and vegetable intake with the incidence of prostate cancer overall , by grade and stage of disease , and prostate cancer death . Lifestyle information for 142,239 men participating in the European Prospect i ve Investigation into Cancer and Nutrition from 8 European countries was collected at baseline . Multivariable Cox regression models were used to estimate hazard ratios ( HRs ) and 95 % confidence intervals ( CIs ) . After an average follow‐up time of 13.9 years , 7,036 prostate cancer cases were identified . Compared with the lowest fifth , those in the highest fifth of total fruit intake had a significantly reduced prostate cancer risk ( HR = 0.91 ; 95 % CI = 0.83–0.99 ; p‐trend = 0.01 ) . No associations between fruit subtypes and prostate cancer risk were observed , except for citrus fruits , where a significant trend was found ( HR = 0.94 ; 95 % CI = 0.86–1.02 ; p‐trend = 0.01 ) . No associations between total and subtypes of vegetables and prostate cancer risk were observed . We found no evidence of heterogeneity in these associations by tumor grade and stage , with the exception of significant heterogeneity by tumor grade ( p heterogeneity<0.001 ) for leafy vegetables . No significant associations with prostate cancer death were observed . The main finding of this prospect i ve study was that a higher fruit intake was associated with a small reduction in prostate cancer risk . Whether this association is causal remains unclear Background Epidemiological evidence for the impact of fruit and vegetable intake on breast cancer risk among the Japanese population s is scarce . Objective The purpose of this study was to evaluate the association between fruit and vegetable intake and breast cancer risk among 47,289 Japanese women . Design The study was conducted under a population -based prospect i ve cohort design . Dietary assessment was performed using a vali date d food frequency question naire . A Cox proportional hazards regression model was used to calculate relative risks ( RRs ) and their corresponding 95 % confidence intervals ( CIs ) . Results During an average of 10.2 years of follow-up , 452 cases of breast cancer were newly diagnosed . No association with breast cancer risk was seen for intake of total fruits and vegetables , cruciferous vegetables , green-leaf vegetables , yellow vegetables , or tomato products in overall or postmenopausal women . Cruciferous vegetable intake was associated with a statistically significant decrease in risk of premenopausal breast cancer [ multivariable-RRQ4 vs. Q1 = 0.64 ( 95 % CI = 0.38–1.10 ; ptrend = .046 ) ] and showed a marginally inverse association with ER+ PR+ tumors [ RRper 100 g increment = 0.64 ( 95 % CI = 0.41–1.00 ) ] . In contrast , positive associations were seen between intake of total fruits and citrus fruits and breast cancer risk in overall and premenopausal women . However , these associations for fruit were all attenuated with additional adjustment for vitamin C intake . Conclusions Our results suggest an overall null association between total fruit and vegetable intake and breast cancer risk . Intake of cruciferous vegetable showed a statistically significant association with a decreased risk of breast cancer among premenopausal women Background Medical nutrition therapy is recognized as an important treatment option in type 2 diabetes . Most guidelines recommend eating a diet with a high intake of fiber-rich food including fruit . This is based on the many positive effects of fruit on human health . However some health professionals have concerns that fruit intake has a negative impact on glycemic control and therefore recommend restricting the fruit intake . We found no studies addressing this important clinical question . The objective was to investigate whether an advice to reduce the intake of fruit to patients with type 2 diabetes affects HbA1c , bodyweight , waist circumference and fruit intake . Methods This was an open r and omized controlled trial with two parallel groups . The primary outcome was a change in HbA1c during 12 weeks of intervention . Participants were r and omized to one of two interventions ; medical nutrition therapy + advice to consume at least two pieces of fruit a day ( high-fruit ) or medical nutrition therapy + advice to consume no more than two pieces of fruit a day ( low-fruit ) . All participants had two consultations with a registered dietitian . Fruit intake was self-reported using 3-day fruit records and dietary recalls . All assessment s were made by the “ intention to treat ” principle . Results The study population consisted of 63 men and women with newly diagnosed type 2 diabetes . All patients completed the trial . The high-fruit group increased fruit intake with 125 grams ( CI 95 % ; 78 to 172 ) and the low-fruit group reduced intake with 51 grams ( CI 95 % ; -18 to −83 ) . HbA1c decreased in both groups with no difference between the groups ( diff . : 0.19 % , CI 95 % ; -0.23 to 0.62 ) . Both groups reduced body weight and waist circumference , however there was no difference between the groups . Conclusions A recommendation to reduce fruit intake as part of st and ard medical nutrition therapy in overweight patients with newly diagnosed type 2 diabetes result ed in eating less fruit . It had however no effect on HbA1c , weight loss or waist circumference . We recommend that the intake of fruit should not be restricted in patients with type 2 diabetes . Trial registration http://www . clinical trials.gov ; Identifier : NCT01010594 Ten normal subjects ingested test meals based on apples , each containing 60 g available carbohydrate . Fibre-free juice could be consumed eleven times faster than intact apples and four times faster than fibre-disrupted purée . Satiety was assessed numerically . With the rate of ingestion equalised , juice was significantly less satisfying than purée , and purée than apples . Plasma-glucose rose to similar levels after all three meals . However , there was a striking rebound fall after juice , and to a lesser extent after purée , which was not seen after apples . Serum-insulin rose to higher levels after juice and purée than after apples . The removal of fibre from food , and also its physical disruption , can result in faster and easier ingestion , decreased satiety , and disturbed glucose homoeostasis which is probably due to inappropriate insulin release . These effects favour overnutrition and , if often repeated , might lead to diabetes mellitus Objective To evaluate the association between fruit and vegetable intake during adolescence and early adulthood and risk of breast cancer . Design Prospect i ve cohort study . Setting Health professionals in the United States . Participants 90 476 premenopausal women aged 27 - 44 from the Nurses ’ Health Study II who completed a question naire on diet in 1991 as well as 44 223 of those women who completed a question naire about their diet during adolescence in 1998 . Main outcome measure Incident cases of invasive breast cancer , identified through self report and confirmed by pathology report . Results There were 3235 cases of invasive breast cancer during follow-up to 2013 . Of these , 1347 cases were among women who completed a question naire about their diet during adolescence ( ages 13 - 18 ) . Total fruit consumption during adolescence was associated with a lower risk of breast cancer . The hazard ratio was 0.75 ( 95 % confidence interval 0.62 to 0.90 ; P=0.01 for trend ) for the highest ( median intake 2.9 servings/day ) versus the lowest ( median intake 0.5 serving/day ) fifth of intake . The association for fruit intake during adolescence was independent of adult fruit intake . There was no association between risk and total fruit intake in early adulthood and total vegetable intake in either adolescence or early adulthood . Higher early adulthood intake of fruits and vegetables rich in α carotene was associated with lower risk of premenopausal breast cancer . The hazard ratio was 0.82 ( 0.70 to 0.96 ) for the highest fifth ( median intake 0.5 serving/day ) versus the lowest fifth ( median intake 0.03 serving/day ) intake . The association with adolescent fruit intake was stronger for both estrogen and progesterone receptor negative cancers than estrogen and progesterone receptor positive cancers ( P=0.02 for heterogeneity ) . For individual fruits and vegetables , greater consumption of apple , banana , and grapes during adolescence and oranges and kale during early adulthood was significantly associated with a reduced risk of breast cancer . Fruit juice intake in adolescence or early adulthood was not associated with risk . Conclusion There is an association between higher fruit intake and lower risk of breast cancer . Food choices during adolescence might be particularly important Squamous head and neck cancers include cancers of the oral cavity , pharynx and larynx are the sixth leading cause of cancer mortality worldwide , result ing in more than 350,000 deaths annually . Intake of fruit and vegetables may protect against head and neck cancer incidence , although few prospect i ve studies have examined this association . We investigated this relation in 490,802 United States participants of the NIH-AARP Diet and Health cohort using Cox proportional hazard models adjusted for potential confounders . During 2,193,751 person years of follow-up from 1995/1996 - 2000 , 787 participants were diagnosed with head and neck cancer . We found an inverse association between total fruit and vegetable intake and head and neck cancer risk ( per serving/day/1,000 calories , Hazard Ratio , 95 % Confidence interval : 0.94 , 0.89 - 0.99 ) . In models mutually adjusted for fruit and vegetable intake , the association was stronger for vegetables ( fifth vs. first quintile : 0.65 , 0.50 - 0.85 ) than for fruits ( fifth vs. first quintile : 0.87 , 0.68 - 1.11 ) . When further subclassified into botanical groups , those in the highest tertile of leguminosae ( dried beans , string beans and peas , 0.80 , 0.67 - 0.96 ) , rosaceae ( apples , peach , nectarines , plums , pears and strawberries , 0.60 , 0.49 - 0.73 ) , solanaceae ( peppers and tomatoes , 0.82 , 0.69 - 0.98 ) and umbelliferae ( carrots , 0.73 , 0.60 - 0.89 ) had decreased risk of head and neck cancer , but no significant associations were seen for 9 other botanical groups . Results from this large prospect i ve observational study are consistent with previous case-control studies and support the hypothesis that total fruit and vegetable intake is associated with reduced risk of head and neck cancer BACKGROUND Because of differences in processing and nutrients , brown rice and white rice may have different effects on risk of type 2 diabetes mellitus . We examined white and brown rice consumption in relation to type 2 diabetes risk prospect ively in the Health Professionals Follow-up Study and the Nurses ' Health Study I and II . METHODS We prospect ively ascertained and up date d diet , lifestyle practice s , and disease status among 39,765 men and 157,463 women in these cohorts . RESULTS After multivariate adjustment for age and other lifestyle and dietary risk factors , higher intake of white rice ( > or = 5 servings per week vs < 1 per month ) was associated with a higher risk of type 2 diabetes : pooled relative risk ( 95 % confidence interval [ CI ] ) , 1.17 ( 1.02 - 1.36 ) . In contrast , high brown rice intake ( > or = 2 servings per week vs < 1 per month ) was associated with a lower risk of type 2 diabetes : pooled relative risk , 0.89 ( 95 % CI , 0.81 - 0.97 ) . We estimated that replacing 50 g/d ( cooked , equivalent to one-third serving per day ) intake of white rice with the same amount of brown rice was associated with a 16 % ( 95 % CI , 9%-21 % ) lower risk of type 2 diabetes , whereas the same replacement with whole grains as a group was associated with a 36 % ( 30%-42 % ) lower diabetes risk [ corrected ] . CONCLUSIONS Substitution of whole grains , including brown rice , for white rice may lower risk of type 2 diabetes . These data support the recommendation that most carbohydrate intake should come from whole grains rather than refined grains to help prevent type 2 diabetes Background / Objectives : Prospect i ve cohort studies have shown that high fruit and vegetable consumption is related to a lower risk of stroke . Whether food processing affects this association is unknown . We evaluated the associations of raw and processed fruit and vegetable consumption independently from each other with 10-year stroke incidence and stroke subtypes in a prospect i ve population -based cohort study in the Netherl and s . Subjects/ Methods : We used data of 20 069 men and women aged 20–65 years and free of cardiovascular diseases at baseline who were enrolled from 1993 to 1997 . Diet was assessed using a vali date d 178-item food frequency question naire . Hazard ratios ( HRs ) were calculated for total , ischemic and hemorrhagic stroke incidence using multivariable Cox proportional hazards models . Results : During a mean follow-up time of 10.3 years , 233 incident stroke cases were documented . Total and processed fruit and vegetable intake were not related to incident stroke . Total stroke incidence was 30 % lower for participants with a high intake of raw fruit and vegetables ( Q4 : > 262 g/day ; HR : 0.70 ; 95 % confidence intervals ( 95 % CIs ) : 0.47–1.03 ) compared with those with a low intake ( Q1 : ⩽92 g/day ) and the trend was borderline significant ( P for trend=0.07 ) . Raw vegetable intake was significantly inversely associated with ischemic stroke ( > 27 vs ⩽27 g/day ; HR : 0.50 ; 95 % CI : 0.34–0.73 ) , and raw fruit borderline significantly with hemorrhagic stroke ( > 120 vs ⩽120 g/day ; HR : 0.53 ; 95 % CI : 0.28–1.01 ) . Conclusions : High intake of raw fruit and vegetables may protect against stroke . No association was found between processed fruit and vegetable consumption and incident stroke The unique composition of green kiwifruit has the potential to benefit CVD risk . The aim of the present study was to investigate the effect of consuming two green kiwifruits daily in conjunction with a healthy diet on plasma lipids and other metabolic markers and to examine response according to APOE genotype in hypercholesterolaemic men . After undergoing a 4-week healthy diet , eighty-five hypercholesterolaemic men ( LDL-cholesterol ( LDL-C ) > 3.0 mmol/l and TAG < 3 mmol/l ) completed an 8-week r and omised controlled cross-over study of two 4-week intervention sequences of two green kiwifruits per d plus healthy diet ( intervention ) or healthy diet alone ( control ) . Anthropometric measures , blood pressure ( BP ) and fasting blood sample s ( plasma lipids , serum apoA1 and apoB , insulin , glucose , high-sensitivity C-reactive protein ( hs-CRP ) ) were taken at baseline , and at 4 and 8 weeks . After the kiwifruit intervention , plasma HDL-cholesterol ( HDL-C ) concentrations were significantly higher ( mean difference 0.04 ; 95 % CI 0.01 , 0.07 mmol/l ; P = 0.004 ) and the total cholesterol (TC):HDL-C ratio was significantly lower ( mean difference 20.5 ; 95 % CI 20.24 , 20.05 mmol/l ; P = 0.002 ) compared with the control . In carriers of the APOE4 allele , TAG decreased significantly ( mean difference -0.18 ; 95 % CI -0.34 , -0.02 mol/l ; P = 0.03 ) with kiwifruit compared with control . There were no significant differences between the two interventions for plasma TC , LDL-C , insulin , glucose , hs-CRP and BP . The small but significant increase in HDL-C and decrease in TC : HDL-C ratio and TAG ( in APOE4 carriers ) suggest that the regular inclusion of green kiwifruit as part of a healthy diet may be beneficial in improving the lipid profiles of men with high cholesterol Although dietary risk factors may differ between localized and advanced prostate cancer , data on associations between the consumption of fruits and vegetables and risk of localized and advanced cancers are limited . We examined associations between fruit and vegetable consumption and risk of prostate cancer in a Japanese population . During 1995–1998 , a vali date d food frequency question naire was administered to 43,475 men aged 45–74 yr . During 321,061 person-years of follow-up until the end of 2004 , 339 cases of prostate cancer were identified . Consumption of fruits or total vegetables was not associated with a decreased risk of total prostate cancer , with corresponding multivariate hazard ratios of the highest vs. lowest quartiles of 1.09 ( 95 % CI = 0.77–1.53 ; trend P = 0.39 ) for fruits and 1.33 ( 95 % CI = 0.93–1.91 ; trend P = 0.52 ) for total vegetables . Also , no association was observed for intake of either fruits or vegetables ( total or any subtype ) with localized or advanced prostate cancer . This prospect i ve cohort study suggests that consumption of fruits or vegetables may not be associated with the risk of either localized or advanced prostate cancer in Japanese men . However , the possibility of confounding by detection bias on the risk of localized cancer could not be totally ruled out BACKGROUND Recent human studies have evaluated the effect of daily apple consumption on plasma cholesterol level , which is recognized as an important risk factor for cardiovascular disease ( CVD ) . Nevertheless , slightly significant effects have been generally registered although consuming more than two apples a day for several weeks . RESULTS This study describes the influence of daily consumption of Annurca apples on the cholesterol levels of mildly hypercholesterolaemic healthy subjects . A monocentric , r and omized , parallel-group , placebo-controlled , 4-month study was conducted . The subjects ( n = 250 ) were r and omly assigned to five treatment groups ( each one of 50 subjects : 28 men and 22 women ) . Four groups were administered one apple per day among the following : Red Delicious , Granny Smith , Fuji , Golden Delicious . The fifth group was asked to consume two Annurca apples per day , since the weight of this cultivar is on average half that of the commercial ones considered in this study . Comparing results , Annurca led to the most significant outcome , allowing a reduction in total and low-density lipoprotein cholesterol levels by 8.3 % and 14.5 % , respectively , and an increase in high-density lipoprotein cholesterol levels by 15.2 % ( all P < 0.001 ) . CONCLUSION Our data would reasonably indicate Annurca apple as a useful tool to contribute to the prevention of CVD risk through normal diet . © 2016 Society of Chemical Industry Epidemiological findings on the association between fruit and vegetable consumption and gastric cancer risk remain inconsistent . The present analysis included 810 prospect ively ascertained non-cardia gastric cancer cases and 1,160 matched controls from the Helicobacter pylori Biomarker Cohort Consortium , which collected blood sample s , demographic , lifestyle , and dietary data at baseline . Conditional logistic regression adjusting for total energy intake , smoking , and H. pylori status , was applied to calculate odds ratios ( ORs ) and 95 % confidence intervals ( CIs ) for gastric cancer risk across cohort- and sex-specific quartiles of fruit and vegetable intake . Increasing fruit intake was associated with decreasing risk of non-cardia gastric cancer ( OR = 0.71 , 95 % CI : 0.52 - 0.95 , p trend = 0.02 ) . Compared to low-fruit consumers infected with CagA-positive H. pylori , high-fruit consumers without evidence of H. pylori antibodies had the lowest odds for gastric cancer incidence ( OR = 0.12 , 95 % CI : 0.06 - 0.25 ) , whereby the inverse association with high-fruit consumption was attenuated among individuals infected with CagA-positive H. pylori ( OR = 0.82 , 95 % CI : 0.66 - 1.03 ) . To note , the small number of H. pylori negative individuals does influence this finding . We observed a weaker , nondose-response suggestion of an inverse association of vegetable intake with non-cardia gastric cancer risk . High fruit intake may play a role in decreasing risk of non-cardia gastric cancer in Asia Many of the flavonoids found in grapes and grape products such as juice or wine have been known to exert antioxidant , anti‐inflammatory , platelet inhibitory and arterial relaxing effects either in vitro , in animal studies and in human trials . This study was design ed to test the effect of Concord grape juice consumption on altering blood pressure in hypertensive patients . Forty subjects were given 5.5 ml/kg body weight/day of either Concord grape juice ( CGJ ) or a calorie‐matched placebo drink every day for 8 weeks . Blood pressure ( BP ) was measured on weeks 0 , 4 and 8 . Compared to baseline , in the CGJ group systolic BP was reduced on average by 7.2 mm Hg ( p = 0.005 ) and diastolic BP was reduced on average by 6.2 mm Hg ( p = 0.001 ) at the end of 8 weeks . Comparable changes in the group getting the placebo product were ‐3.5 mm Hg ( NS ) and ‐3.2 mm Hg ( p = 0.05 ) Consuming Concord grape juice , which is high in polyphenolic compounds , may favorably affect BP in hypertensive individuals Fruit and vegetable ( F&V ) intake is considered as probably protective against overall cancer risk , but results in previous studies are not consistent for thyroid cancer ( TC ) . The purpose of this study is to examine the association between the consumption of fruits , vegetables , fruit juices and differentiated thyroid cancer risk within the European Prospect i ve Investigation into Cancer and Nutrition ( EPIC ) study . The EPIC study is a cohort including over half a million participants , recruited between 1991 and 2000 . During a mean follow‐up of 14 years , 748 incident first primary differentiated TC cases were identified . F&V and fruit juice intakes were assessed through vali date d country‐specific dietary question naires . Hazard ratios ( HRs ) and 95 % confidence intervals ( CIs ) were estimated using Cox regression models adjusted for potential confounding factors . Comparing the highest versus lowest quartile of intake , differentiated TC risk was not associated with intakes of total F&V ( HR : 0.89 ; 95 % CI : 0.68–1.15 ; p‐trend = 0.44 ) , vegetables ( HR : 0.89 ; 95 % CI : 0.69–1.14 ; p‐trend = 0.56 ) , or fruit ( HR : 1.00 ; 95 % CI : 0.79–1.26 ; p‐trend = 0.64 ) . No significant association was observed with any individual type of vegetable or fruit . However , there was a positive borderline trend with fruit juice intake ( HR : 1.23 ; 95 % CI : 0.98–1.53 ; p‐trend = 0.06 ) . This study did not find any significant association between F&V intakes and differentiated TC risk ; however a positive trend with fruit juice intake was observed , possibly related to its high sugar content |
13,871 | 31,574,022 | In patients treated with ICIs , irAEs predict survival and response .
Although this correlation can not be fully explained , it may be related to the strongest T-cell activation | Immune-related adverse events ( irAEs ) are autoimmune-toxic effects associated with immune checkpoint inhibitors ( ICIs ) used for the treatment of advanced solid tumors .
We performed a systematic review and meta- analysis of the published literature to assess the outcome for cancer patients treated with ICIs who develop irAEs . | BACKGROUND Blockade of programmed death 1 ( PD-1 ) , an inhibitory receptor expressed by T cells , can overcome immune resistance . We assessed the antitumor activity and safety of BMS-936558 , an antibody that specifically blocks PD-1 . METHODS We enrolled patients with advanced melanoma , non-small-cell lung cancer , castration-resistant prostate cancer , or renal-cell or colorectal cancer to receive anti-PD-1 antibody at a dose of 0.1 to 10.0 mg per kilogram of body weight every 2 weeks . Response was assessed after each 8-week treatment cycle . Patients received up to 12 cycles until disease progression or a complete response occurred . RESULTS A total of 296 patients received treatment through February 24 , 2012 . Grade 3 or 4 drug-related adverse events occurred in 14 % of patients ; there were three deaths from pulmonary toxicity . No maximum tolerated dose was defined . Adverse events consistent with immune-related causes were observed . Among 236 patients in whom response could be evaluated , objective responses ( complete or partial responses ) were observed in those with non-small-cell lung cancer , melanoma , or renal-cell cancer . Cumulative response rates ( all doses ) were 18 % among patients with non-small-cell lung cancer ( 14 of 76 patients ) , 28 % among patients with melanoma ( 26 of 94 patients ) , and 27 % among patients with renal-cell cancer ( 9 of 33 patients ) . Responses were durable ; 20 of 31 responses lasted 1 year or more in patients with 1 year or more of follow-up . To assess the role of intratumoral PD-1 lig and ( PD-L1 ) expression in the modulation of the PD-1-PD-L1 pathway , immunohistochemical analysis was performed on pretreatment tumor specimens obtained from 42 patients . Of 17 patients with PD-L1-negative tumors , none had an objective response ; 9 of 25 patients ( 36 % ) with PD-L1-positive tumors had an objective response ( P=0.006 ) . CONCLUSIONS Anti-PD-1 antibody produced objective responses in approximately one in four to one in five patients with non-small-cell lung cancer , melanoma , or renal-cell cancer ; the adverse-event profile does not appear to preclude its use . Preliminary data suggest a relationship between PD-L1 expression on tumor cells and objective response . ( Funded by Bristol-Myers Squibb and others ; Clinical Trials.gov number , NCT00730639 . ) Treating advanced or recurrent melanoma remains a challenge . Cancer cells can evade the immune system by blocking T‐cell activation through overexpression of the inhibitory receptor programmed death 1 ( PD‐1 ) lig and s. The PD‐1 inhibitor nivolumab blocks the inhibitory signal in T cells , thus overcoming the immune resistance of cancer cells . Nivolumab has shown promising anticancer activity in various cancers . We carried out a single‐arm , open‐label , multicenter , phase II study to investigate the efficacy and safety of nivolumab in previously untreated Japanese patients with advanced melanoma . Twenty‐four patients with stage III/IV or recurrent melanoma were enrolled and received i.v . nivolumab 3 mg/kg every 2 weeks until disease progression or unacceptable toxicity . The primary endpoint was overall response rate evaluated by an independent radiology review committee . The independent radiology review committee‐assessed overall response rate was 34.8 % ( 90 % confidence interval , 20.8–51.9 ) , and the overall survival rate at 18 months was 56.5 % ( 90 % confidence interval , 38.0–71.4 ) . Treatment‐related adverse events ( AEs ) of grade 3 or 4 only occurred in three patients ( 12.5 % ) . Two patients discontinued nivolumab because of AEs , but all AEs were considered manageable by early diagnosis and appropriate treatment . Subgroup analyses showed that nivolumab was clinical ly beneficial and tolerable regardless of BRAF genotype , and that patients with treatment‐related select AEs and with vitiligo showed tendency for better survival . In conclusion , nivolumab showed favorable efficacy and safety profiles in Japanese patients with advanced or recurrent melanoma , with or without BRAF mutations . ( Trial registration no. JapicCTI‐142533 . Objectives To evaluate the prevalence and type of rheumatic immune-related adverse events ( irAEs ) in patients receiving immune checkpoint inhibitors ( ICIs ) , as well as the correlation with tumour response . Methods This was a single-centre prospect i ve observational study including all cancer patients receiving ICIs . The occurrence of irAEs and tumour response was assessed on a regular basis . Patients who experienced musculoskeletal symptoms were referred to the department of rheumatology for clinical evaluation and management . Results From September 2015 to May 2017 , 524 patients received ICIs and 35 were referred to the department of rheumatology ( 6.6 % ) . All but one of the rheumatic irAEs occurred with anti-programmed cell death protein 1(PD-1)/PD-1 lig and 1(PD-L1 ) antibodies , with a median exposure time of 70 days . There were two distinct clinical presentations : ( 1 ) inflammatory arthritis ( 3.8 % ) mimicking either rheumatoid arthritis ( n=7 ) , polymyalgia rheumatica ( n=11 ) or psoriatic arthritis ( n=2 ) and ( 2 ) non-inflammatory musculoskeletal conditions ( 2.8 % ; n=15 ) . One patient with rheumatoid arthritis was anti-cyclic citrullinated peptide ( anti-CCP ) positive . Nineteen patients required glucocorticoids , and methotrexate was started in two patients . Non-inflammatory disorders were managed with non-steroidal anti-inflammatory drugs , analgesics and /or physiotherapy . ICI treatment was pursued in all but one patient . Patients with rheumatic irAEs had a higher tumour response rate compared with patients without irAEs ( 85.7 % vs 35.3 % ; P<0.0001 ) . Conclusion Since ICIs are used with increasing frequency , knowledge of rheumatic irAEs and their management is of major interest . All patients were responsive either to low-to-moderate doses of prednisone or symptomatic therapies and did not require ICI discontinuation . Furthermore , tumour response was significantly higher in patients who experienced rheumatic irAEs Background Programmed cell death protein-1 ( PD-1 ) blockade therapies have demonstrated durable responses and prolonged survival in a variety of malignancies . Treatment is generally well tolerated although immune-related adverse events ( irAEs ) can occur . Autoimmune thyroid dysfunction is among the most common irAE , but an assessment of the clinical , mechanistic , and immunologic features has not been previously described . Patient and methods Patients with advanced non-small-cell lung cancer ( NSCLC ) treated with pembrolizumab at Memorial Sloan Kettering Cancer Center ( n = 51 ) as part of KEYNOTE-001 ( NCT01295827 ) were included . Thyroid function test and anti-thyroid antibodies were assessed prospect ively at each study visit , beginning before the first treatment . Frequency of development of thyroid dysfunction , association with anti-thyroid antibodies , clinical course , and relationship with progression-free survival and overall survival to treatment with pembrolizumab was evaluated . Results Of 51 patients treated , 3 were hypothyroid and 48 were not at baseline . Ten of 48 [ 21 % , 95 % confidence interval ( CI ) 10 % to 35 % ] patients developed thyroid dysfunction requiring thyroid replacement . Anti-thyroid antibodies were present in 8 of 10 patients who developed thyroid dysfunction , compared with 3 of 38 who did not ( 80 % versus 8 % , P < 0.0001 ) . Thyroid dysfunction occurred early ( median , 42 days ) in the pembrolizumab course , and a majority ( 6 of 10 patients ) experienced brief , transient hyperthyroidism preceding the onset of hypothyroidism ; no persistent hyperthyroidism occurred . Both hyperthyroidism and hypothyroidism were largely asymptomatic . Overall survival with pembrolizumab was significantly longer in subjects who developed thyroid dysfunction ( hazard ratio , 0.29 ; 95 % CI 0.09 - 0.94 ; P = 0.04 ) . Conclusions Thyroid dysfunction during pembrolizumab treatment of NSCLC is common and is characterized by early-onset , frequently preceded by transient hyperthyroidism , closely associated with anti-thyroid antibodies , and may be associated with improved outcomes . The presence of antibody-mediated toxicity in T-cell-directed therapy suggests an under-recognized impact of PD-1 biology in modulating humoral immunity BACKGROUND Atezolizumab is a humanised antiprogrammed death-lig and 1 ( PD-L1 ) monoclonal antibody that inhibits PD-L1 and programmed death-1 ( PD-1 ) and PD-L1 and B7 - 1 interactions , reinvigorating anticancer immunity . We assessed its efficacy and safety versus docetaxel in previously treated patients with non-small-cell lung cancer . METHODS We did a r and omised , open-label , phase 3 trial ( OAK ) in 194 academic or community oncology centres in 31 countries . We enrolled patients who had squamous or non-squamous non-small-cell lung cancer , were 18 years or older , had measurable disease per Response Evaluation Criteria in Solid Tumors , and had an Eastern Cooperative Oncology Group performance status of 0 or 1 . Patients had received one to two previous cytotoxic chemotherapy regimens ( one or more platinum based combination therapies ) for stage IIIB or IV non-small-cell lung cancer . Patients with a history of autoimmune disease and those who had received previous treatments with docetaxel , CD137 agonists , anti-CTLA4 , or therapies targeting the PD-L1 and PD-1 pathway were excluded . Patients were r and omly assigned ( 1:1 ) to intravenously receive either atezolizumab 1200 mg or docetaxel 75 mg/m2 every 3 weeks by permuted block r and omisation ( block size of eight ) via an interactive voice or web response system . Co primary endpoints were overall survival in the intention-to-treat ( ITT ) and PD-L1-expression population TC1/2/3 or IC1/2/3 ( ≥1 % PD-L1 on tumour cells or tumour-infiltrating immune cells ) . The primary efficacy analysis was done in the first 850 of 1225 enrolled patients . This study is registered with Clinical Trials.gov , number NCT02008227 . FINDINGS Between March 11 , 2014 , and April 29 , 2015 , 1225 patients were recruited . In the primary population , 425 patients were r and omly assigned to receive atezolizumab and 425 patients were assigned to receive docetaxel . Overall survival was significantly longer with atezolizumab in the ITT and PD-L1-expression population s. In the ITT population , overall survival was improved with atezolizumab compared with docetaxel ( median overall survival was 13·8 months [ 95 % CI 11·8 - 15·7 ] vs 9·6 months [ 8·6 - 11·2 ] ; hazard ratio [ HR ] 0·73 [ 95 % CI 0·62 - 0·87 ] , p=0·0003 ) . Overall survival in the TC1/2/3 or IC1/2/3 population was improved with atezolizumab ( n=241 ) compared with docetaxel ( n=222 ; median overall survival was 15·7 months [ 95 % CI 12·6 - 18·0 ] with atezolizumab vs 10·3 months [ 8·8 - 12·0 ] with docetaxel ; HR 0·74 [ 95 % CI 0·58 - 0·93 ] ; p=0·0102 ) . Patients in the PD-L1 low or undetectable subgroup ( TC0 and IC0 ) also had improved survival with atezolizumab ( median overall survival 12·6 months vs 8·9 months ; HR 0·75 [ 95 % CI 0·59 - 0·96 ] ) . Overall survival improvement was similar in patients with squamous ( HR 0·73 [ 95 % CI 0·54 - 0·98 ] ; n=112 in the atezolizumab group and n=110 in the docetaxel group ) or non-squamous ( 0·73 [ 0·60 - 0·89 ] ; n=313 and n=315 ) histology . Fewer patients had treatment-related grade 3 or 4 adverse events with atezolizumab ( 90 [ 15 % ] of 609 patients ) versus docetaxel ( 247 [ 43 % ] of 578 patients ) . One treatment-related death from a respiratory tract infection was reported in the docetaxel group . INTERPRETATION To our knowledge , OAK is the first r and omised phase 3 study to report results of a PD-L1-targeted therapy , with atezolizumab treatment result ing in a clinical ly relevant improvement of overall survival versus docetaxel in previously treated non-small-cell lung cancer , regardless of PD-L1 expression or histology , with a favourable safety profile . FUNDING F. Hoffmann-La Roche Ltd , Genentech , OBJECTIVES Patients treated with nivolumab often experience its unique adverse events , called immune-related adverse events ( irAEs ) . Regarding the mechanisms of immune-checkpoint inhibitors ( ICIs ) , the occurrence of irAEs may also reflect antitumor responses . Here , we report the clinical correlation between irAEs and efficacy in NSCLC patients treated with nivolumab . MATERIAL S AND METHODS Between December 2015 and February 2017 , 38 advanced NSCLC patients were treated in our institution . All the patients were enrolled in our single-institutional , prospect i ve , observational cohort study ( UMIN000024414 ) . IrAEs were defined as having a potential immunological basis that required more frequent monitoring and potential intervention . We divided the patients into two groups ( irAEs group or no-irAEs group ) and evaluated the objective response rate ( ORR ) and progression-free survival ( PFS ) . RESULTS The median age of the patients was 68.5 years ( range 49 - 86 years ) ; male/female ratio was 28/10 ; squamous/non-squamous cell carcinoma cases were 10/28 ; performance status was 0 - 1/2/3 , 7/26/5 . Among the overall population , ORR was 23.7 % and median PFS was 91days . At the data cutoff , 14 irAEs were observed . The most common irAE was interstitial pneumonia ( n=5 ) . Other irAEs were hypothyroidism ( n=4 ) , hyperthyroidism , hypopituitarism , liver dysfunction , rash , and elevated thyroid stimulating hormone levels ( n=1 , each ) . Patients with irAEs had significantly higher ORRs compared with no-irAE patients ( 63.6 % versus 7.4 % , p < 0.01 ) . Similarly , the PFS among irAE patients was longer ( median : not reached [ 95 % confidence interval { CI } : 91days to not applicable ] ) than no-irAE patients ( median 49days [ 95 % CI : 36 - 127days ] , hazard ratio [ HR ] 0.10 [ 95 % CI : 0.02 - 0.37 , p<0.001 ] ) . L and mark analysis of patients who achieved PFS ≥60days demonstrated similar tendencies , but this was not significant ( HR 0.28 [ 95 % CI : 0.04 - 1.46 ] , p=0.13 ) . CONCLUSION There was a correlation between irAE and efficacy in NSCLC patients treated with nivolumab Patients with metastatic renal cell cancer and metastatic melanoma treated with high-dose interleukin-2-based immunotherapy were prospect ively evaluated for the development of vitiligo . All patients seen in the Surgery Branch , NCI Immunotherapy Clinic , who had been followed for at least 1 year were evaluated . Of 104 patients with metastatic renal cancer none developed vitiligo , though vitiligo was seen in 11 of 74 ( 15 % ) patients with metastatic melanoma ( p2 = 0.0001 ) . No vitiligo was seen in 27 patients who did not respond to immunotherapy , although vitiligo was seen in 11 of 43 ( 26 % ) melanoma patients who had an objective response to IL-2-based immunotherapy ( p2 = 0.0002 ) . These findings provide further evidence that the presence of a growing melanoma can sensitize patients to melanocyte-differentiation antigens and that the immune response against these antigens is associated with cancer regression in patients undergoing immunotherapy Breast cancer has not previously been considered a highly immunogenic cancer . Observations of tumour-infiltrating lymphocytes ( TILs ) in and around neoplastic cells in tumour sample s , and associations with improved pathological complete response and clinical survival end points have changed our perspective on this . Lymphocytic infiltrates have long been observed in breast cancer ; however , more recently , retrospective analysis of prospect ively collected tissue sample s from clinical trials has demonstrated the potential role of host immunosurveillance in influencing the biology of breast cancer . This association appears to be strongest in triple negative and HER2 positive breast cancer subtypes . Contrastingly , the association in luminal tumours is less clear , and is potentially limited by substantial tumoural heterogeneity . Several method ologies have been employed to quantify , and describe the composition of TILs , each with its own advantages and disadvantages . The results of these analyses have been generally consistent , and valuable efforts are currently underway to st and ardise the evaluation of TILs toward a universal approach . More technical methods of TIL characterisation remain important in the research setting . The evaluation of TILs becomes increasingly relevant with the emerging role of immunotherapy in breast cancer . Early phase trials of checkpoint blockade show promising results ; however , it is likely that some patients will require combination treatments to maximise therapeutic benefits . Equally , some patients may not derive any benefit from immunotherapies . This underscores the importance of the development of relevant predictive biomarkers . As a key representative of the immune interaction between host and tumour , lymphocytic infiltrates are ideally placed for continued research into the determinants of immunogenicity , and response to immunotherapeutic approaches . In this review , we will discuss the current method ologies of evaluation , and the clinical relevance of TILs . Additionally , we discuss the emerging role of immunotherapy in breast cancer , and the future of TIL characterisation in this context OBJECTIVES To assess inter-rater reliability and validity of the Newcastle Ottawa Scale ( NOS ) used for method ological quality assessment of cohort studies included in systematic review s. STUDY DESIGN AND SETTING Two review ers independently applied the NOS to 131 cohort studies included in eight meta-analyses . Inter-rater reliability was calculated using kappa ( κ ) statistics . To assess validity , within each meta- analysis , we generated a ratio of pooled estimates for each quality domain . Using a r and om-effects model , the ratios of odds ratios for each meta- analysis were combined to give an overall estimate of differences in effect estimates . RESULTS Inter-rater reliability varied from substantial for length of follow-up ( κ = 0.68 , 95 % confidence interval [ CI ] = 0.47 , 0.89 ) to poor for selection of the nonexposed cohort and demonstration that the outcome was not present at the outset of the study ( κ = -0.03 , 95 % CI = -0.06 , 0.00 ; κ = -0.06 , 95 % CI = -0.20 , 0.07 ) . Reliability for overall score was fair ( κ = 0.29 , 95 % CI = 0.10 , 0.47 ) . In general , review ers found the tool difficult to use and the decision rules vague even with additional information provided as part of this study . We found no association between individual items or overall score and effect estimates . CONCLUSION Variable agreement and lack of evidence that the NOS can identify studies with biased results underscore the need for revisions and more detailed guidance for systematic review ers using the NOS Purpose Approximately 40 % of patients with advanced melanoma who received nivolumab combined with ipilimumab in clinical trials discontinued treatment because of adverse events ( AEs ) . We conducted a retrospective analysis to assess the efficacy and safety of nivolumab plus ipilimumab in patients who discontinued treatment because of AEs . Methods Data were pooled from phase II and III trials of patients who received nivolumab 1 mg/kg plus ipilimumab 3 mg/kg , every 3 weeks for four doses , followed by nivolumab monotherapy 3 mg/kg every 2 weeks ( N = 409 ) . Efficacy was assessed in all r and omly assigned patients who discontinued because of AEs during the induction phase ( n = 96 ) and in those who did not discontinue because of AEs ( n = 233 ) . Safety was assessed in treated patients who discontinued because of AEs ( n = 176 ) at any time and in those who did not discontinue because of AEs ( n = 231 ) . Results At a minimum follow-up of 18 months , median progression-free survival was 8.4 months for patients who discontinued treatment because of AEs during the induction phase and 10.8 months for patients who did not discontinue because of AEs ( P = .97 ) . Median overall survival had not been reached in either group ( P = .23 ) . The objective response rate was 58.3 % for patients who discontinued because of AEs during the induction phase and 50.2 % for patients who did not discontinue . The vast majority of grade 3 or 4 AEs occurred during the induction phase , with most resolving after appropriate management . Conclusion Efficacy outcomes seemed similar between patients who discontinued nivolumab plus ipilimumab treatment because of AEs during the induction phase and those who did not discontinue because of AEs . Therefore , even after discontinuation , many patients may continue to derive benefit from combination therapy Background : Cutaneous adverse events are common with programmed death 1 (PD‐1)/programmed death lig and 1 ( PD‐L1 ) inhibitors . However , the nature of the specific cutaneous adverse event of dermatitis has not been investigated across various PD‐1/PD‐L1 inhibitors . Oncologic outcomes potentially associated with dermatitis are not well characterized . Objective : To assess the nature of dermatitis after exposure to a PD‐1/PD‐L1 inhibitor and oncologic outcomes associated with dermatitis . Methods : Retrospective , matched , case‐control study conducted at a single academic center . Results : The most common histologic patterns were lichenoid dermatitis ( 50 % ) and spongiotic dermatitis ( 40 % ) . The overall tumor response rate was 65.0 % for the case patients and 17.0 % for the controls ( P = .0007 ) ( odds ratio , 7.3 ; 95 % confidence interval , 2.3‐23.1 ) . The progression‐free survival and overall survival times were significantly longer for the case patients than for the controls by Kaplan‐Meier analysis ( P < .0001 and .0203 , respectively ) . Limitations : The retrospective design and relatively small sample size precluded matching for all cancer types . Conclusions : Lichenoid and spongiotic dermatitis associated with PD‐1/PD‐L1 inhibitors could be a sign of robust immune response and improved oncologic outcomes . The value of PD‐1/PD‐L1–related dermatitis in predicting cancer outcomes awaits investigation through prospect i ve multicenter studies for specific cancer types R and omized prospect i ve studies on patients with metastatic non‐small‐cell lung cancers ( NSCLCs ) showed that anti‐programmed death‐1 ( PD‐1 ) agents notably improved 2‐year overall survival ( OS ) rates , compared to docetaxel . NSCLC patients now receive nivolumab and irradiation , concurrently or not . However , little is known about the safety of this combination , even though the pre clinical model suggested a possible synergic effect . We analyzed NSCLC patients treated with radiotherapy and nivolumab according to former 's timing BACKGROUND Immune checkpoint inhibitors ( ICIs ) are available for first- and further lines of treatment of patients with advanced non-small-cell lung cancer ( NSCLC ) . These treatments are associated with adverse events called immune-related adverse events ( IRAEs ) . The incidence , diagnosis , and treatment of IRAEs are quite acknowledged ; however , the link between IRAEs and the efficacy of ICIs requires further clarification . The objectives of this study were to assess the association between IRAEs incidence and severity and ICIs efficacy in patients with advanced NSCLC . METHODS In this retrospective study , clinical , biological , treatment , and outcome data were collected from patients with advanced NSCLC who received at least 1 cycle of ICIs from April 2013 to February 2017 . The primary endpoint was to assess the association of IRAEs incidence with overall survival ( OS ) . Secondary endpoints were the association of IRAEs with progression-free survival ( PFS ) , objective response rate ( ORR ) , and disease control rate ( DCR ) . RESULTS Overall , 270 patients were studied . The median OS was 14 months , median PFS was 2.6 months , ORR was 13 % , and DCR was 51 % . OS , PFS , and ORR were significantly better for patients with IRAEs compared with patients with no IRAEs , translating to median OS not reached versus 8.21 months , respectively ( hazard ratio , 0.29 ; 95 % confidence interval [ CI ] , 0.18 - 0.46 ; P < .001 ) ; PFS was 5.2 versus 1.97 months ( hazard ratio , 0.42 ; 95 % CI , 0.32 - 0.57 ; P < .001 ) ; and ORR was 212.9 % versus 5.7 % ( odds ratio , 4.9 ; 95 % CI , 2.18 - 11.05 ; P < .001 ) . CONCLUSIONS This report presents the largest case series showing longer OS and PFS and better ORR when IRAEs occurred in a population of patients with advanced NSCLC treated with ICIs . The biological background for this phenomenon is being explored prospect ively BACKGROUND Programmed death 1 ( PD-1 ) protein , a T-cell coinhibitory receptor , and one of its lig and s , PD-L1 , play a pivotal role in the ability of tumor cells to evade the host 's immune system . Blockade of interactions between PD-1 and PD-L1 enhances immune function in vitro and mediates antitumor activity in pre clinical models . METHODS In this multicenter phase 1 trial , we administered intravenous anti-PD-L1 antibody ( at escalating doses ranging from 0.3 to 10 mg per kilogram of body weight ) to patients with selected advanced cancers . Anti-PD-L1 antibody was administered every 14 days in 6-week cycles for up to 16 cycles or until the patient had a complete response or confirmed disease progression . RESULTS As of February 24 , 2012 , a total of 207 patients --75 with non-small-cell lung cancer , 55 with melanoma , 18 with colorectal cancer , 17 with renal-cell cancer , 17 with ovarian cancer , 14 with pancreatic cancer , 7 with gastric cancer , and 4 with breast cancer -- had received anti-PD-L1 antibody . The median duration of therapy was 12 weeks ( range , 2 to 111 ) . Grade 3 or 4 toxic effects that investigators considered to be related to treatment occurred in 9 % of patients . Among patients with a response that could be evaluated , an objective response ( a complete or partial response ) was observed in 9 of 52 patients with melanoma , 2 of 17 with renal-cell cancer , 5 of 49 with non-small-cell lung cancer , and 1 of 17 with ovarian cancer . Responses lasted for 1 year or more in 8 of 16 patients with at least 1 year of follow-up . CONCLUSIONS Antibody-mediated blockade of PD-L1 induced durable tumor regression ( objective response rate of 6 to 17 % ) and prolonged stabilization of disease ( rates of 12 to 41 % at 24 weeks ) in patients with advanced cancers , including non-small-cell lung cancer , melanoma , and renal-cell cancer . ( Funded by Bristol-Myers Squibb and others ; Clinical Trials.gov number , NCT00729664 . ) |
13,872 | 25,479,008 | AUTHORS ' CONCLUSIONS Based on high quality evidence from studies whose overall risk of bias is low , intravenous prophylactic antibiotics for cesarean administered preoperatively significantly decreases the incidence of composite maternal postpartum infectious morbidity as compared with administration after cord clamp .
There were no clear differences in adverse neonatal outcomes reported .
Women undergoing cesarean delivery should receive antibiotic prophylaxis preoperatively to reduce maternal infectious morbidities . | BACKGROUND Given the continued rise in cesarean birth rate and the increased risk of surgical site infections after cesarean birth compared with vaginal birth , effective interventions must be established for prevention of surgical site infections .
Prophylactic intravenous ( IV ) antibiotic administration 60 minutes prior to skin incision is recommended for abdominal gynecologic surgery ; however , administration of prophylactic antibiotics has traditionally been withheld until after neonatal umbilical cord clamping during cesarean delivery due to the concern for potential transfer of antibiotics to the neonate .
OBJECTIVES To compare the effects of cesarean antibiotic prophylaxis administered preoperatively versus after neonatal cord clamp on postoperative infectious complications for both the mother and the neonate . | BACKGROUND Independent risk factors for surgical site infection ( SSI ) after cesarean section have not been well documented , despite the large number of cesarean sections performed and the relatively common occurrence of SSI . OBJECTIVE To determine independent risk factors for SSI after low transverse cesarean section . DESIGN Retrospective case-control study . SETTING Barnes-Jewish Hospital , a 1,250-bed tertiary care hospital . PATIENTS A total of 1,605 women who underwent low transverse cesarean section during the period from July 1999 to June 2001 . METHODS Using the International Classification of Diseases , Ninth Revision , Clinical Modification diagnosis codes for SSI or wound complication and /or data on antibiotic use during the surgical hospitalization or at readmission to the hospital or emergency department , we identified potential cases of SSI in a cohort of patients who underwent a low transverse cesarean section . Cases of SSI were verified by chart review using the definitions from the Centers for Disease Control and Prevention 's National Nosocomial Infections Surveillance System . Control patients without SSI or endomyometritis were r and omly selected from the population of patients who underwent cesarean section . Independent risk factors for SSI were determined by logistic regression . RESULTS SSIs were identified in 81 ( 5.0 % ) of 1,605 women who underwent low transverse cesarean section . Independent risk factors for SSI included development of subcutaneous hematoma after the procedure ( adjusted odds ratio [ aOR ] , 11.6 [ 95 % confidence interval [ CI ] , 4.1 - 33.2 ] ) , operation performed by the university teaching service ( aOR , 2.7 [ 95 % CI , 1.4 - 5.2 ] ) , and a higher body mass index at admission ( aOR , 1.1 [ 95 % CI , 1.0 - 1.1 ] ) . Cephalosporin therapy before or after the operation was associated with a significantly lower risk of SSI ( aOR , 0.2 [ 95 % CI , 0.1 - 0.5 ] ) . Use of staples for skin closure was associated with a marginally increased risk of SSI . CONCLUSIONS These independent risk factors should be incorporated into approaches for the prevention and surveillance of SSI after surgery OBJECTIVE The purpose of this prospect i ve study was to determine whether the timing of prophylactic antibiotics at cesarean delivery influences maternal/neonatal infectious morbidity . STUDY DESIGN In this double-blind placebo-controlled trial , cefazolin was given at skin incision ( group A ) or at cord clamping ( group B ) . Patients were eligible for the trial if they had labored and required a cesarean delivery . RESULTS Over a 30-month period 303 patients with singleton pregnancies entered the trial ; 153-group A , 149-group B. Demographics , indication for cesarean delivery ( P = .54 ) , and operative time ( P = .999 ) , as well as rates of endometritis ( RR 0.67 , 95 % CI 0.42 - 1.07 ) , wound infection ( RR 0.84 , 95 % CI 0.45 - 1.55 ) , neonatal sepis ( RR 1.28 , 95 % CI 0.91 - 1.79 ) , and NICU admissions ( RR 1.28 , 95 % CI 0.91 - 1.79 ) were similar between the 2 groups . CONCLUSION There was no difference in maternal infectious morbidity whether antibiotics were given before skin incision or at cord clamping In an ongoing prospect i ve study at 2 hospitals , 114 cesarean section patients were studied to determine whether giving ampicillin after umbilical cord clamping is as effective as perioperative ampicillin in reducing maternal postoperative morbidity . The same patients have also been studied to determine the effect of prophylactic cesarean section ampicillin on the newborn . Results have shown that prophylactic ampicillin initiated after cord clamping is as effective in reducing maternal morbidity as ampicillin initiated prior to the surgery . There is also no evidence from our study that the transplacental passage of prophylactic ampicillin increases immediate or delayed neonatal infections CONTEXT Perioperative antibiotic prophylaxis during elective cesarean delivery at term to reduce postoperative maternal infectious morbidity is generally used but may not be effective on the basis of the available data . Also , the optimal timing of prophylactic antibiotic administration is unclear . OBJECTIVE To compare the effectiveness of cefazolin administered before skin incision vs cefazolin administered after umbilical cord clamping vs placebo in a 3-arm r and omized trial . The primary objective of the study was to compare postoperative infectious morbidity , defined as wound infection , endometritis , or urinary tract infection ( primary end point ) , in women with cefazolin vs placebo . The comparison between the 2 arms administering cefazolin before skin incision vs after umbilical cord clamping was a secondary end point . DESIGN Double-blind , prospect i ve , r and omized , placebo-controlled trial . SETTING The Department of Obstetrics and Gynecology , Medical University of Vienna , Vienna , Austria . PATIENTS We recruited 1112 women undergoing elective cesarean delivery at term from March 1 , 2004 , through January 31 , 2010 . INTERVENTIONS In group 1 , cefazolin ( 2 g ) was administered 20 to 30 minutes before skin incision . In group 2 , cefazolin ( 2 g ) was administered immediately after clamping of the cord . In group 3 , placebo was administered before skin incision . RESULTS The primary outcome was observed in 18 of 370 women in group 1 ( 4.9 % ) and in 14 of 371 women in group 2 ( 3.8 % ) , whereas it was noted in 45 of 371 women in group 3 ( 12.1 % ) ( P < .001 for group 1 plus group 2 vs group 3 ) . The number needed to treat to avoid 1 primary outcome was 13 ( 95 % CI , 9 to 24 ) . Between groups 1 and 2 , there was no statistically significant difference regarding postoperative infectious morbidity ( P = .60 ) . CONCLUSION We were able to demonstrate the usefulness in elective cesarean delivery of prophylactic cefazolin vs placebo in reducing postoperative maternal infectious morbidity Objective The aim of this study was to determine whether the timing of prophylactic antibiotics at cesarean delivery influences maternal and neonatal infectious morbidity . Study design This was a prospect i ve , r and omized trial . Four hundred patients that underwent elective cesarean section between June and December 2007 formed the study population . Eleven patients were excluded from the study because they needed transfusion during the cesarean section . The population was divided into two groups : Group A , antibiotic prophylaxis was applied to 194 women before skin incision and Group B , antibiotic prophylaxis was applied to 195 women after umbilical cord clamping . The occurrence of endomyometritis/endometritis , wound infection , febrile morbidity , total infectious morbidity , and neonatal complications were compared . Results There were 389 patients enrolled . No demographic differences were observed between groups . No significant difference was found between the groups for total infectious morbidity [ relative risk ( RR ) 1.39 , 95 % confidence interval ( CI ) 0.71–2.69 ] and endometritis ( RR 1.40 , 95 % CI 0.43–4.51 ) . There was no increase in neonatal sepsis ( RR 1.47 , 95 % CI 0.61–3.53 ) , sepsis workup ( RR 1.35 , 95 % CI 0.75–2.42 ) , need for neonatal intensive care ( RR 1.77 , 95 % CI 0.51–6.16 ) , and intensive care stay period ( P = 0.16 ) . Conclusions Time of antibiotic prophylaxis application does not change maternal infectious morbidity in cesarean section deliveries . Preoperative prophylaxis application does not affect neonate morbidity rates as stated in literature OBJECTIVE To assess whether changing the entire surgical team 's gloves intraoperatively , after delivery of the placenta , would reduce the rate of postcesarean wound infection . STUDY DESIGN Women who underwent cesarean delivery were r and omized to a group where the surgical team changed the surgical gloves after delivery of the placenta or to a control group , where surgical gloves were not changed during the cesarean procedure . RESULTS Ninety-two patients were r and omized to 2 groups of 46 patients each . The group where the surgical team changed their gloves had significantly less serosanguineous drainage 24 hours after surgery ( 3 vs. 8 patients , 8.3 % vs. 22.2 % , P = .2 , RR 2.7 , CI 0.7 , 12.4 ) and fewer wound infections ( 2 vs. 9 women , 5.5 % vs. 25 % , P = .05 , RR 4.5 , CI 0.982 , 29.8 ) . CONCLUSION Obstetricians may decrease the number of postcesarean wound infections by having the entire team change surgical gloves after delivery of the placenta We compared maternal and neonatal outcomes in women who received prophylactic antibiotics prior to skin incision to those who received antibiotics at cord clamp . We performed a r and omized clinical trial at two sites . Eligible women included those undergoing nonemergency cesarean at 36 weeks ' gestation or greater . Subjects were r and omized ( permuted blocks ) into one of two treatments : " preoperative antibiotics " ( cefazolin 1 g given < 30 minutes prior to skin incision ) or " intraoperative antibiotics " ( cefazolin 1 g at cord clamping ) . Patients who reported an allergy to penicillin received clindamycin 900 mg . The trial primary outcome was a composite of maternal infectious morbidities , defined as having any one of the following : ( 1 ) postoperative fever ( defined as oral temperature > 38 ° C on two separate occasions more than 6 hours apart , after the initial 24-hour postoperative period ) ; ( 2 ) wound infection ( defined as purulent discharge from the incision ) ; ( 3 ) endomyometritis ( defined as fundal tenderness and fever malodorous lochia , fever ) ; ( 4 ) urinary tract infection ( defined as fever , positive urine culture ) . We enrolled a total of 434 subjects in this study , with 217 in each group . Overall , we found no difference in composite maternal infectious morbidity between those who received antibiotics preoperatively and those who received antibiotics at cord clamp ( relative risk = 1.2 , 95 % confidence interval 0.7 to 1.5 ) . Neonatal outcomes were also similar between the two intervention arms . The rate of suspected sepsis was similar between the two groups . There were no cases of antibiotic resistance in the neonates . Either preoperative antibiotic therapy or antibiotic administration after cord clamp is a reasonable clinical method for reducing the risk of postcesarean infectious morbidity The objective of this study was to test the hypothesis that 1 g of cefazolin administered preoperatively is no more effective than the same dose administered after cord clamping in preventing postcesarean infectious morbidity . Ninety consecutive laboring subjects undergoing cesarean delivery at > or = 37 weeks gestation were r and omized by computer to receive 1 g of cefazolin intravenously preoperatively or after cord clamping in a double-blinded , placebo-controlled study . The 2 groups were compared for differences in maternal and neonatal demographics , and intrapartum and operative characteristics associated with postcesarean infection . Primary maternal outcome variables were endometritis or wound infection . Secondary outcomes included intra-abdominal abscess formation , septic pelvic thrombophlebitis , pneumonia , or urinary tract infection . Neonatal outcomes included sepsis screens , sepsis , pneumonia , and meningitis . Subjects were followed 6 weeks postoperatively for late complications . Subjects receiving cefazolin preoperatively or after cord clamping had similar maternal and neonatal demographics , and intrapartum and operative characteristics . One patient in the former group experienced both endometritis and wound infection . In the latter group , 2 wound infections and 1 case of endometritis occurred ( P = 0.35 ) . There were no secondary maternal infections . Two infants treated for pneumonia and 2 other infants readmitted with febrile illnesses were born to mothers receiving cefazolin preoperatively . Overall , 8 neonates were evaluated for suspected sepsis and all had negative studies . Six of these infants ' mothers received cefazolin preoperatively ( P = 0.28 ) . In conclusion , 1 gram of cefazolin preoperatively is no more effective than the same dose administered after cord clamping in preventing postcesarean infectious morbidity , but is associated with a trend toward increased suspected sepsis in the newborn . However , this trend may be related to differences between the study groups ' risk factors for infection Objective : The purpose was to determine the effect of the timing of prophylactic antibiotics for cesarean section on post-operative infectious complications . Study Design : This was a prospect i ve , double-blinded , r and omized controlled trial in which patients were r and omized to receive cefazolin or clindamycin either before skin incision or after cord clamp . The primary outcome was maternal infectious morbidity at 6 weeks postpartum , a composite infectious outcome , which included endometritis , urinary tract infection , wound infection and pneumonia . Result : Data on 896 women were analyzed ; 449 r and omized to skin incision , 447 to cord clamp . Postpartum infections were seen in a total of 8.4 % of patients . Timing of antibiotic administration did not significantly affect any maternal postpartum infection rates or selected neonatal outcomes . Conclusion : Our results suggest that , in a largely non-laboring population , the timing of prophylactic antibiotic administration does not impact post-operative infectious complications of the mother . Despite being one of the largest r and omized controlled trials to address this question , our study still lacked sufficient power to make definitive conclusions Objective To compare the influence on caesarean section morbidity of uterine exteriorisation or Purpose To compare the efficacy of ceftriaxone before skin incision and after cord clamping in preventing post-operative infectious morbidity and neonatal outcome in elective caesarean section and to determine the effect of antibiotic prophylaxis before skin incision on neonatal outcome . Methods Our study was a r and omised controlled trial conducted among 874 women undergoing elective caesarean section from October 2010 to July 2012 . These women were r and omly categorised into two groups with 437 women in each group . Group 1 received single dose of ceftriaxone 1 g intravenously 15–45 min before skin incision . Group 2 received the antibiotic after cord clamping . Primary outcome measures were maternal post-operative infectious morbidities like surgical site wound infection , febrile morbidity , endometritis , urinary tract infections and neonatal sepsis . Results were analysed using Chi-square test and unpaired t test . Results Surgical site wound infection occurred in 3 women in group 1 ( 0.7 % ) and 6 women in group 2 ( 1.4 % ) . Fever occurred in 9 women in group 1 ( 2.1 % ) and 5 in group 2 ( 1.1 % ) with the p value of 0.419 , not statistically significant . Urinary tract infection occurred in 9 women in group 1 ( 2.1 % ) and 7 women in group 2 ( 1.6 % ) with the p value of 0.801 . None of the women in either group developed endometritis . About 20 neonates [ 10 neonates ( 2.3 % ) in group 1 and 10 neonates ( 2.3 % ) in group 2 ] required NICU admission after caesarean delivery . The reasons for admission were respiratory distress , prematurity and congenital anomaly . About 0.9 % of neonates in group 1 and 1.8 % in group 2 developed neonatal sepsis with positive blood culture ( p = 0.388 ) . Conclusion Timing of administration of prophylactic antibiotics for elective caesarean section either before skin incision or after cord clamping did not have significant difference in the occurrence of post-operative infectious morbidity . No adverse neonatal outcome was observed in women who received the antibiotic before skin incision OBJECTIVE The objective of the study was to determine whether the administration of cefazolin prior to skin incision was superior to administration at the time of umbilical cord clamping for the prevention of postcesarean infectious morbidity . STUDY DESIGN This was a prospect i ve , r and omized , double-blind , placebo-controlled trial . Study subjects received cefazolin 15 - 60 minutes prior to incision and controls received cefazolin at the time of cord clamping . The occurrence of endomyometritis , wound infection , total infectious morbidity , and neonatal complications were compared . RESULTS There were 357 subjects enrolled . No demographic differences were observed between groups . There were decreased total infectious morbidity in the study group ( relative risk [ RR ] = 0.4 , 95 % confidence interval [ CI ] 0.18 to 0.87 ) , decreased endometritis ( RR = 0.2 , 95 % CI 0.15 to 0.94 ) . No increase in neonatal sepsis ( P = .99 ) , sepsis workups ( P = .96 ) , or length of stay ( P = .17 ) was observed . CONCLUSION Administration of prophylactic cefazolin prior to skin incision result ed in a decrease in both endomyometritis and total postcesarean infectious morbidity , compared with administration at the time of cord clamping . This dosing did not result in increased neonatal septic workups or complications AIM Cesarean delivery is associated with a significantly higher postoperative infection rate than that following vaginal birth and other surgical procedures . This study compared whether antibiotic prophylaxis administered preoperatively was more effective in preventing infectious morbidity following cesarean delivery than administration at cord clamping . MATERIAL AND METHODS In a r and omized comparative trial , 953 women with a period of gestation of more than 34 weeks , scheduled to have cesarean section , were r and omly assigned to the prophylactic single-dose antibiotic administration either preoperatively ( study group ) or at cord clamping ( control group ) . Primary outcome measure was postoperative maternal infectious morbidity and secondary outcome measures were neonatal complications , and postoperative maternal hospital stay and stay of neonates in the neonatal intensive care unit . RESULTS Wound complications in the form of in duration s , erythema and discharge , were significantly fewer in the study group as compared to the control group ( 10/476 vs 25/477 , P = 0.010 , conditional maximum likelihood estimate of odds ratio = 0.388 and 95 % confidence interval = 0.175 - 0.805 ) . Women in the study group also had fewer incidents of endomyometritis when compared to the control group ( 1.47 % vs 3.56 % ; P = 0.041 ; conditional maximum likelihood estimate of odds ratio = 0.404 ) . There was no significant difference in neonatal outcomes between the two groups . Mean postoperative stay of mothers in hospital was significantly shorter in the study group ( P = 0.009 , 95 % confidence interval = -0.368 to -0.052 ) but neonatal intensive care unit stay of neonates was similar in both groups . CONCLUSION Administration of prophylactic antibiotic at 30 - 60 min before skin incision result ed in better maternal outcome when infectious morbidity and postoperative hospital stay were concerned , without influencing the neonatal outcome Objective : To determine the impact of two skin preparation methods and two techniques of pelvic irrigation on the incidence of post-cesarean endometritis and wound infection in an indigent patient population . Methods : A r and omized study was performed in 100 cesarean patients . Subjects were assigned to one of four groups , involving either st and ard skin preparation ( povidone- iodine [ 7.5 % ] scrub followed by povidone-iodine [ 10 % ] solution ) or special skin preparation ( 5-minute scrub with parachlorometaxylenol followed by povidone scrub and solution ) , and either normal saline or antibiotic ( cefazolin sodium , 1 g in 500 mL normal saline ) irrigation of the pelvis and subcutaneous tissue at uterine and fascial closure . Four groups of patients were formed : st and ard skin preparation plus normal saline irrigation , st and ard preparation plus antibiotic irrigation , special preparation plus normal saline irrigation , and special preparation plus antibiotic irrigation . Results : Endometritis occurred significantly more often in the combined groups that did not include antibiotic irrigation than in the combined groups involving antibiotic irrigation ( P < .001 ) . In contrast , comparison of skin preparation methods between povidone-iodine alone versus preparation including parachlorometaxylenol indicated no significant difference ( P = .22 ) . Conclusion : Skin preparation with an antibacterial scrub in addition to st and ard povidone-iodine scrub and solution does not appear to play as significant a role in the reduction of post-cesarean endometritis or wound infection as does intraoperative pelvic irrigation with antibiotic solution BACKGROUND R and omized , controlled trials have shown that prophylactic antibiotics are effective in preventing surgical-wound infections . However , it is uncertain how the timing of antibiotic administration affects the risk of surgical-wound infection in actual clinical practice . METHODS We prospect ively monitored the timing of antibiotic prophylaxis and studied the occurrence of surgical-wound infections in 2847 patients undergoing elective clean or " clean-contaminated " surgical procedures at a large community hospital . The administration of antibiotics 2 to 24 hours before the surgical incision was defined as early ; that during the 2 hours before the incision , as preoperative ; that during the 3 hours after the incision , as perioperative ; and that more than 3 but less than 24 hours after the incision , as postoperative . RESULTS Of the 1708 patients who received the prophylactic antibiotics preoperatively , 10 ( 0.6 percent ) subsequently had surgical-wound infections . Of the 282 patients who received the antibiotics perioperatively , 4 ( 1.4 percent ) had such infections ( P = 0.12 ; relative risk as compared with the preoperatively treated group , 2.4 ; 95 percent confidence interval , 0.9 to 7.9 ) . Of 488 patients who received the antibiotics postoperatively , 16 ( 3.3 percent ) had wound infections ( P less than 0.0001 ; relative risk , 5.8 ; 95 percent confidence interval , 2.6 to 12.3 ) . Finally , of 369 patients who had antibiotics administered early , 14 ( 3.8 percent ) had wound infections ( P less than 0.0001 ; relative risk , 6.7 ; 95 percent confidence interval , 2.9 to 14.7 ) . Stepwise logistic-regression analysis confirmed that the administration of antibiotics in the preoperative period was associated with the lowest risk of surgical-wound infection . CONCLUSIONS We conclude that in surgical practice there is considerable variation in the timing of prophylactic administration of antibiotics and that administration in the two hours before surgery reduces the risk of wound infection Objectives . The aim of this study was to document the true incidence of post‐cesarean surgical site infections ( SSI ) , according to the definition of the US Centers for Disease Control and Prevention ( CDC ) , and to identify independent risk factors for infection . Design . Prospect i ve population ‐based cohort study in Norway . Setting . Sykehuset Asker og Bærum HF , a secondary community hospital , associated with the University of Oslo ( UiO ) , Norway , accounting for 2,000 deliveries per year . Participants . All cesarean deliveries during a 12‐month period from September 2003 . Main outcome measures . Rate and risk factors for SSI . Results . The total rate of SSI was 8.9 % , with an observation period of 30 days post‐operatively , compared to 1.8 % registered at hospital discharge . The total response rate was 100 % . There was no significant difference in SSI rate in elective or emergency cesarean section ( CS ) , respectively . All SSI were superficial . We found 2 significant independent risk factors : operating time ≥38 min and body mass index ( BMI ) > 30 . Conclusion . The rate of SSI is underestimated if the observation time is limited to the hospital stay . Operating time exceeding 38 min substantially increases the risk of SSI . The finding of no significant difference in SSI rate between elective and emergency CS should lead to a different approach concerning the use of antibiotics : subgroup at risk ( operating time ≥38 min and BMI > 30 ) may benefit from antibiotics in relation to the operation , whether the CS is an emergency or elective operation Preoperative skin preparation before cesarean section using a one-minute alcohol wash followed by application of an iodophor-impregnated adhesive film was evaluated in a prospect i ve , r and omized , controlled study of 79 patients . The iodophor film was as effective as the five-minute iodophor scrub followed by an iodophor wash , as determined by a reduction in skin bacterial counts . Clinical infectious morbidity was no different between the treatment and control groups , although the study was too small to draw statistically significant conclusions in this respect . This study demonstrated the antimicrobial effectiveness of a new , more rapid method of pre-operative skin preparation before cesarean section as compared to a longer , traditional method . This new , rapid method offers advantages for many patients undergoing abdominal delivery The efficacy of two r and omized antibiotic prophylactic schedules with ceftazidime ( group A : single preoperative 2 g intramuscular dose ; group B : 3 perioperative 1 g intramuscular doses every 6 h ) was evaluated in 200 pregnant women undergoing cesarean section . Postoperative complications were observed in 9 cases ( 4 in group A and 5 in group B ; p = NS ) . Analysis of possible risk factors revealed 1 ) a relationship between postoperative morbidity and overweight ( body mass index above 30 ) in group A only ; 2 ) a possible contributory effect of duration of labor ( more than 6 h ) in group A ; and 3 ) a possible effect of duration of rupture of the membranes ( more than 6 h ) in group B only . The results obtained lead to the conclusion that single-dose prophylaxis with ceftazidime is as effective as short-term 3-dose ceftazidime prophylaxis in preventing post-cesarean complications Abstract Objective : To determine the best time to administer prophylactic antibiotics at Cesarean delivery in order to reduce the postoperative maternal infectious morbidity in a low re source setting . Material and Methods : One hundred term primigravidae with singleton pregnancy were recruited and r and omly allocated to two equal groups . Each woman received 2 g intravenous Cefazoline . Women in Group I received it prior to skin incision while those in Group II had it immediately after cord clamping . We measured the following outcome parameters : ( 1 ) Surgical site wound infection ; ( 2 ) Endometritis and ( 3 ) Urinary tract infection . Results : There was no significant difference in any of the patients ’ characteristics between both groups . In Group I , three cases developed surgical site infections but four in Group II ( p > 0.05 ) . In Group I , the infected cases had Cesarean because of malpresentations while in Group II , two cases had Cesarean because of patients ’ request , one because of maternal heart disease and one due to intra-uterine growth restriction . Seven and nine cases had urinary tract infection in Groups I and II , respectively , ( p > 0.05 ) . Conclusion : Prophylactic antibiotic administration either prior to surgery or after cord clamping is probably equally effective in reducing the postoperative infectious morbidity after Cesarean in low re source setting |
13,873 | 32,249,144 | There appeared to be no difference in mean time to union and mean Disabilities of the Arm , Shoulder and H and scores between the treatment groups .
No difference was found between effect estimates form observational studies and RCTs .
This systematic review shows that satisfactory results can be achieved with both conservative and operative management ; however , operative treatment reduces the risk of nonunion compared with conservative treatment , with comparable reintervention rates ( for indications other than nonunion ) .
Furthermore , operative treatment results in a similar permanent radial nerve palsy rate , despite its inherent additional surgery-related risks . | BACKGROUND This meta- analysis aim ed to compare conservative vs. operative treatment for humeral shaft fractures in terms of the nonunion rate , reintervention rate , permanent radial nerve palsy rate , and functional outcomes .
Secondarily , effect estimates from observational studies were compared with estimates of r and omized clinical trials ( RCTs ) . | BACKGROUND Humeral shaft fractures account for 1 - 3 % of all fractures and 20 % of the fractures involving the humerus . The aim of the current study was to compare the outcome after operative and non-operative treatment of humeral shaft fractures , by comparing the time to radiological union and the rates of delayed union and complications . METHODS All patients aged 16 years or over treated for a humeral shaft fracture during a 5-year period were included in this retrospective analysis ; periprosthetic and pathological fractures were excluded . Radiographs and medical charts were retrieved and review ed in order to collect data on fracture classification , time to radiographic consolidation and the occurrence of adverse events . RESULTS A total of 186 patients were included ; 91 were treated non-operatively and 95 were treated operatively . Mean age was 58.7 ± 1.5 years and 57.0 % were female . In 83.3 % of the patients , only the humerus was affected . A fall from st and ing height was the most common cause of the fracture ( 72.0 % ) . Consolidation time varied from a median of 11 - 28 weeks . The rate of radial nerve palsy in both groups was similar : 8.8 % versus 9.5 % . In 5.3 % of the operatively treated patients , the palsy result ed from the operation . Likewise , delayed union rates were similar in both groups : 18.7 % following non-operative treatment versus 18.9 % following surgery . CONCLUSION The data indicated that consolidation time and complication rates were similar after operative and non-operative treatment . A prospect i ve r and omised clinical trial comparing non-operative with operative treatment is needed in order to examine other aspects of outcome , meaning shoulder and elbow function , postoperative infection rates , trauma-related quality of life and patient satisfaction Background : Nonoperative treatment has historically been considered the st and ard for fractures of the shaft of the humerus . Minimally invasive bridge-plate osteo synthesis for isolated humeral shaft fractures has been proven to be a safe technique , with good and reproducible results . This study was design ed to compare clinical and radiographic outcomes between patients who had been treated with bridge plate osteo synthesis and those who had been managed nonoperatively with a functional brace . Methods : A prospect i ve r and omized trial was design ed and included 110 patients allocated to 1 of 2 groups : surgery with a bridge plate or nonoperative treatment with a functional brace . The primary outcome was the Disabilities of the Arm , Shoulder and H and ( DASH ) score at 6 months . The score on the Short Form-36 ( SF-36 ) life- quality question naire , complications of treatment , Constant-Murley score for the shoulder , pain level , and radiographic results were assessed as secondary outcomes . Participants were assessed at 2 weeks ; 1 , 2 , and 6 months ; and 1 year after the interventions . Results : The mean DASH score of the bridge plate group was statistically superior to that of the functional brace group ( mean scores , 10.9 and 16.9 , respectively ; p = 0.046 ) only at 6 months . The bridge plate group also had a significantly more favorable nonunion rate ( 0 % versus 15 % ) and less mean residual angular displacement seen on the anteroposterior radiograph ( 2.0 ° versus 10.5 ° ) ( both p < 0.05 ) . No difference between the groups was detected with regard to the SF-36 score , pain level , Constant-Murley score , or angular displacement seen on the lateral radiograph . Conclusions : This trial demonstrates that , compared with functional bracing , surgical treatment with a bridge plate has a statistically significant advantage , of uncertain clinical benefit , with respect to self-reported outcome ( DASH score ) at 6 months , nonunion rate , and residual deformity in the coronal plane as seen on radiographs . Level of Evidence : Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence Background : Because of specific method ological difficulties in conducting r and omized trials , surgical research remains dependent predominantly on observational or non‐r and omized studies . Few vali date d instruments are available to determine the method ological quality of such studies either from the reader 's perspective or for the purpose of meta‐ analysis . The aim of the present study was to develop and vali date such an instrument 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 PURPOSE The aim of this study is to examine the demographic factors , functional outcome and radiological data to predict the outcome of humeral diaphyseal fractures . METHODS We performed a prospect i ve study on a consecutive series of 110 patients of 16 years or over , who had sustained a humeral diaphyseal fracture . There were 42 males and 68 females , with an average age of 59 years ( range 16 - 93 years ) . A total of 72 % sustained low-energy injuries , and 89 patients ( 81 % ) were primarily treated non-operatively . Shoulder function was assessed using the Neer 's and Constant 's scores at 8 weeks , 3 months , 6 months and 1 year after injury . Muscle strength was determined isokinetically using a Biodex System 2 dynamometer . Non-union was defined as a failure to bridge at least three cortices and persistence of tenderness or mobility at the fracture site 16 weeks after fracture . RESULTS Sixteen patients ( 17 % ) had non-union at 16 weeks , while 80 had achieved union and a further 14 were lost to follow-up . After stepwise multiple linear regression was performed to isolate independent factors affecting outcome , only the presence of a proximal diaphyseal fracture was found to predict non-union along with a poor Neer 's score at 8 and 12 weeks . Poor Neer 's scores could be predicted at 26 weeks by age ( P<0.05 ) , previous stroke ( P<0.001 ) and non-union ( P<0.001 ) . At 52 weeks both age ( P<0.01 ) and previous stroke ( P<0.01 ) were independently predictive of poorer Neer 's scores . Malunion of any degree had no detectable effect on function . CONCLUSIONS Our results indicate that non-union of humeral diaphyseal fractures can be predicted in the presence of a proximal third fracture with a Neer 's score of less than 45 by 12 weeks after fracture . Early surgery improves early function , but this is not a lasting effect . Poor shoulder function is predicted by increasing age , proximal third fractures and non-union . We recommend that surgery to promote union be considered at 12 weeks after fracture in fit patients with fractures of the proximal third of the humerus , poor Neer 's scores and no radiographic progression to union Objective : The primary aim was to describe the epidemiology of the Holstein-Lewis humeral shaft fracture , its association with radial nerve palsy , and the outcome regarding recovery from the radial nerve palsy and fracture healing . The secondary aim was to analyze the long-term functional outcome . Setting : Six major hospitals in Stockholm County . Design : Descriptive study . Retrospective assessment of radial nerve recovery and fracture healing . Prospect i ve assessment of functional outcome . Patients : Twenty-seven patients with a 12A1.3 humeral shaft fracture according to the OTA classification satisfying the criteria of a Holstein-Lewis fracture in a population of 358 patients with 361 traumatic humeral shaft fractures . Intervention : Nonoperative or operative treatment according to the decision of the attending orthopaedic surgeon . Main Outcome Measurements : Recovery of the radial nerve , fracture healing , and functional outcome according to the Short Musculoskeletal Function Assessment ( SMFA ) . Results : The Holstein-Lewis humeral shaft fracture constitutes 7.5 % of all humeral shaft fractures and was associated with an increased risk of acute radial nerve palsy compared with other types of humeral shaft fractures , 22 % versus 8 % ( P < 0.05 ) . The fractures of 6 of the 7 operatively treated patients healed after the primary surgical procedure while 1 fracture healed after revision surgery . The fractures of all patients treated nonoperatively healed without any further intervention . All 6 radial nerve palsies ( 2 patients treated nonoperatively and 4 operatively ) recovered . The functional outcome according to the SMFA was good with no differences between the nonoperatively and operatively treated patients : SMFA dysfunction index 7.6 and 9.7 , respectively , and SMFA bother index 6.1 and 6.8 , respectively . Conclusions : The Holstein-Lewis humeral shaft fracture was associated with a significantly increased risk of acute radial nerve palsy . The overall outcome regarding fracture healing , radial nerve recovery , and function was very good regardless of the primary treatment modality , that is , operative or nonoperative treatment . The indication for primary operative intervention in this fracture type appears to be relative Summary . A comparison was made between 44 humeral fractures treated conservatively with functional bracing ( Group 1 ) and 45 treated by operation with a locking nail ( Group 2 ) . Thirty-eight of the 44 patients in Group 1 ( 86 % ) and 22 of the 45 patients in Group 2 ( 47 % ) regained full movement of the shoulder joint . The functional end results were somewhat better in Group 1 although over 90 % of patients in both groups were able to clasp their fingers behind their necks and to reach up their backs without restriction . Two patients developed a pseudarthrosis in Group 1 , and 2 patients in Group 2 required operative revision due to a haematoma in 1 case and as a result of an infection in the other . There were 6 cases of primary radial nerve damage in both groups , and 6 had to be decompressed operatively . Residual sensory and motor disturbance remained in 2 patients in Group 1 . Both methods are useful for the treatment of humeral shaft fractures . We advocate functional bracing as the method of choice if no contraindications exist . Résumé . 99 fractures de la diaphyse humérale ont été analysées , do nt 44 ont été traitées par brassard et 45 par clou intramédullaire . 86 % du groupe : traitement conservateur et 47 % du groupe : traitement opératoire présentaient un mouvement illimité de l’épaule , t and is que plus de 90 % des deux groupes arrivaient à toucher la nuque ( rotation externe en abduction ) et la sacrum ( rotation interne en adduction ) avec la main du bras blessé . Il y a eut deux pseudarthroses dans le groupe conservateur . Dans le groupe opératoire deux interventions chirurgicales ont été nécessaires en raison d’une infection et d’une hémorragie . Les deux groupes présentaient chacun 6 cas de paralysie primaire du nerf radial avec une décompression chirurgicale consécutive dans 6 cas . Des déficits moteurs et sensitifs persistaient chez deux malades du groupe conservateur . Les deux méthodes sont efficaces pour le traitement des fractures de la diaphyse de l’humérus . En cas d’absence des contre-indications nous recomm and ons le traitement par brassard comme traitement de premier choix BACKGROUND : For many years it has been cl aim ed that observational studies find stronger treatment effects than r and omized , controlled trials . We compared the results of observational studies with those of r and omized , controlled trials . METHODS : We search ed the Abridged Index Medicus and Cochrane data bases to identify observational studies reported between 1985 and 1998 that compared two or more treatments or interventions for the same condition . We then search ed the Medline and Cochrane data bases to identify all the r and omized , controlled trials and observational studies comparing the same treatments for these conditions . For each treatment , the magnitudes of the effects in the various observational studies were combined by the Mantel-Haenszel or weighted analysis -of-variance procedure and then compared with the combined magnitude of the effects in the r and omized , controlled trials that evaluated the same treatment . RESULTS : There were 136 reports about 19 diverse treatments , such as calcium-channel-blocker therapy for coronary artery disease , appendectomy , and interventions for subfertility . In most cases , the estimates of the treatment effects from observational studies and r and omized , controlled trials were similar . In only 2 of the 19 analyses of treatment effects did the combined magnitude of the effect in observational studies lie outside the 95 percent confidence interval for the combined magnitude in the r and omized , controlled trials . CONCLUSIONS : We found little evidence that estimates of treatment effects in observational studies reported after 1984 are either consistently larger than or qualitatively different from those obtained in r and omized , controlled trials This prospect i ve multicenter study conducted by the German section of the AO International analyzes 302 fractures of the humeral shaft , 170 ( 56 % ) of which were operated upon and 132 ( 44 % ) , treated conservatively . Among those operated upon , 3.5 % developed infections and 10 % showed paresis of the radial nerve . In contrast , the only complication in the group treated conservatively was pseudarthrosis , in 1 case . However , further analysis revealed that complications were distributed unequally among the centers and the most complications were reported from only a few hospitals . We were able to contact 173 ( 57 % ) patients for follow-up . Results of operative and conservative treatment were compared for similar fractures . Both techniques result ed in predominantly good to excellent results . The somewhat inferior results in the group operated upon were explained by the higher percentage of associated local injuries and concomitant injuries to other organs . The results of this study were compared with those of other recent studies , and recommendations were established for the operative and conservative treatment of fractures of the humeral shaft |
13,874 | 27,708,552 | Summary estimates obtained by meta- analysis showed that HRQL in patients with perennial HDM allergy was significantly worse than that of patients with seasonal pollen allergy , when measured by both disease-specific and generic HRQL instruments , and was reflected by an impact on both physical and mental health .
A systematic review of cost data on AR and AA in selected European countries demonstrated that the majority of the economic burden was indirectly caused by high levels of absenteeism and presenteeism ; there was little or no evidence of increasing or decreasing cost trends . | This meta- analysis compared the health-related quality of life ( HRQL ) of patients with allergic rhinitis ( AR ) and /or allergic asthma ( AA ) caused by perennial house dust mite ( HDM ) versus AR and /or AA caused by seasonal pollen allergy . | To assess quality of life and cost-effectiveness of additional acupuncture treatment for allergic rhinitis , patients were r and omly allocated to 2 groups ; both received usual care , but one group received an additional 10 acupuncture sessions . Quality of life ( according to the SF-36 Health Survey ) , and direct and indirect costs , were assessed at baseline and after 3 months , and the incremental cost-effectiveness ratio of acupuncture treatment was calculated . This German study ( December 2000-June 2004 ) involved 981 patients ( 64 % women , mean age 40.9 years ( st and ard deviation , 11.2 ) ; 36 % men , mean age 43.2 years ( st and ard deviation , 13.0 ) ) . At 3 months , quality of life was higher in the acupuncture group than in the control group ( mean Physical Component Score 51.99 ( st and ard error ( SE ) , 0.33 ) vs. 48.25 ( SE , 0.33 ) , P < 0.001 ; mean Mental Component Score 48.55 ( SE , 0.42 ) vs. 45.35 ( SE , 0.42 ) , respectively , P < 0.001 ) . Overall costs in the acupuncture group were significantly higher than those in the control group ( Euro ( euro ; 1 euro = US $ 1.27 ) 763 , 95 % confidence interval : 683 , 844 vs. 332 euro , 95 % confidence interval : 252 , 412 ; mean difference 432 euro , 95 % confidence interval : 318 , 545 ) . The incremental cost-effectiveness ratio was 17,377 euro per quality -adjusted life year ( women , 10,155 euro ; men , 44,871 euro ) and was robust in sensitivity analyses . Acupuncture , supplementary to routine care , was beneficial and , according to international benchmarks , cost-effective . However , because of the study design , it remains unclear whether the effects are acupuncture specific Asthma and rhinitis are common chronic conditions that affect adults of working age . Little is known about their relative impacts on work loss and decreased productivity . Using r and om digit telephone dialing , we carried out a population -survey of adults in Northern California aged 18 - 50 years . We interviewed 125 persons with asthma ( with or without concomitant rhinitis ) and 175 persons with rhinitis alone . Study eligibility was based on subject report of a physician 's diagnosis of asthma and /or a rhinitis-related condition . Any adult labor force participation since condition onset was lower among those with asthma ( 88 % ) than among those with rhinitis alone ( 97 % ) ( P = 0.002 ) . In contrast , among those still employed , decreased job effectiveness was more frequently reported in the rhinitis group ( 43 of 121 ; 36 % ) compared to those with asthma ( 14 of 72 ; 19 % ) ( P = 0.02 ) . Condition-attributed lost work was common in both groups , with more than 20 % reporting one or more complete or partial work days lost in the 4 weeks previous to interview . Taking into account age , gender , race , and smoking status , those with asthma were more likely to have no labor force participation after diagnosis ( OR = 3.0 ; 95 % CI 1.1 - 7.7 ) and less likely to report decreased job effectiveness among those remaining employed ( OR = 0.4 ; 95 % CI 0.2 - 0.9 ) . Excluding subjects from the rhinitis group most likely to have unreported asthma based on past medication use had little impact on these associations . Both asthma and rhinitis negatively affect work productivity . Those with asthma are less likely to be employed at all , while among those remaining on the job , rhinitis is a more potent cause of decreased work effectiveness . The economic impact of asthma and rhinitis and related conditions may be under-appreciated Background : Environmental control has been put forward as an integral part of the management of house dust mite ( HDM ) allergy in sensitized patients . To vali date this statement allergic disorders involved in HDM allergy – allergic asthma , rhinitis and atopic eczema/dermatitis syndrome ( AEDS ) – should be taken together and studied in terms of the efficacy of environmental control . Because a generic quality of life question naire exceeds the border of disease , this may be used as major outcome parameter Background Modification of allergens by glutaraldehyde in extracts used for immunotherapy reduces the risk for side effects , but therapeutic efficacy of such extracts requires further evaluation . The aim of this study was to evaluate the efficacy and safety of immunotherapy with PURETHAL Mites ( PM ) , a single-strength glutaraldehyde-modified aluminum hydroxide – adsorbed extract of house-dust mites ( HDM ) . Methods In a multicenter , r and omized , placebo-controlled double-blind setting , HDM-allergic subjects ( n = 140 ) were treated with modified allergen extract or placebo over a 1-year period . The primary outcome parameter was a combined symptom and medication score ( clinical index score [ CIS ] ) . Secondary efficacy parameters were the result of a titrated conjunctival provocation test ( CPT ) , rhinitis/rhinoconjunctivitis quality of life ( RQL ) score , and serum concentrations of IgE and IgG against specific HDM allergens and a documentation of adverse events ( AE ) . Results We evaluated 140 patients ( 66 treatment and 74 placebo ) for clinical efficacy . The allergoid treatment for 1 year result ed in significantly greater CIS improvement and higher RQL scores . The response threshold in the titrated CPT ( p = 0.009 ) and the serum concentrations of IgG4 ( p < 0.001 ) against Dermatophagoides pteronyssinus allergens after treatment were also significantly different between groups . In total , 88 patients ( 46 PM/42 placebo ) out of a safety population of 145 reported 278 ( 158 PM/120 placebo ) AE . Except for local reactions , no specific AE appeared to be associated with PURETHAL Mites ( HAL-Allergy , Leiden , The Netherl and s ) . Conclusion The findings of this study indicate that allergen injection therapy with modified HDM extract is superior to placebo in allergic rhinitis therapy . The treatment was well tolerated and no serious drug-related AE were observed The effect of cetirizine on quality of life ( QOL ) in subjects with perennial allergic rhinitis ( PAR ) has been previously evaluated using generic instruments . While generic QOL tools are used across various conditions , disease-specific instruments evaluate the impact of treatment on areas that are affected by that particular condition . This study evaluated the effect of cetirizine on symptom severity and health-related QOL , using a disease-specific instrument , in adults with PAR . This r and omized , double-blind , placebo-controlled study was conducted at 15 U.S. centers outside the pollen allergy season . After a 1-week placebo run-in period , qualified subjects aged 18 - 65 years with PAR were r and omized to once-daily cetirizine 10 mg ( n = 158 ) or placebo ( n = 163 ) for 4 weeks . Change from baseline in total symptom severity complex ( TSSC ) and overall Rhinitis Quality of Life Question naire ( RQLQ ) scores were primary efficacy end points . Cetirizine produced significantly greater improvements in mean TSSC for each treatment week ( p < 0.05 ) and for the entire 4-week treatment period ( p = 0.005 ) compared with placebo . After 4 weeks , cetirizine-treated subjects reported significantly greater overall improvement in RQLQ scores compared with placebo-treated subjects ( p = 0.004 ) . After 1 week , cetirizine produced significant improvements in the nasal symptoms , practical problems , and activities RQLQ domain scores compared with placebo ( p < 0.05 ) . After 4 weeks , cetirizine-treated subjects reported significant reductions in these RQLQ domain scores and in emotion domain scores compared with placebo-treated subjects ( p < 0.05 ) . Cetirizine 10 mg daily produced significant improvements in symptom severity and allergic rhinitis-related QOL compared with placebo in adults with PAR Objective To assess the efficacy of enzyme potentiated desensitisation in the treatment of severe summer hay fever poorly controlled by pharmacotherapy . Design Double blind r and omised placebo controlled parallel group study . Setting Hospital in Hampshire . Participants 183 participants aged between 18 and 64 with a history of severe summer hay fever for at least two years ; all were skin prick test positive to timothy grass pollen . 90 r and omised to active treatment ; 93 r and omised to placebo . Interventions Active treatment : two injections of enzyme potentiated desensitisation , given between eight and 11 weeks apart , each comprising 200 Fishman units of β glucuronidase , 50 pg 1,3-cyclohexanediol , 50 ng protamine sulphate , and a mixed inhaled allergen extract ( pollen mixes for trees , grasses , and weeds ; allergenic fungal spores ; cat and dog d and ers ; dust and storage mites ) in a total volume of 0.05 ml of buffered saline . Placebo : two injections of 0.05 ml buffered saline solution . Main outcome measures Proportion of problem-free days ; global rhinoconjunctivitis quality of life scores assessed weekly during pollen season . Results The active treatment group and the placebo group did not differ in the proportion of problem-free days , quality of life scores , symptom severity scores , change in quantitative skin prick provocation threshold , or change in conjunctival provocation threshold . No clinical ly significant adverse reactions occurred . Conclusions Enzyme potentiated desensitisation showed no treatment effect in this study Background Allergic Rhinitis is an inflammatory disease which is characterised by burdensome nasal and /or ocular symptoms . This study aim ed to assess the impact of symptoms ( number of symptom-free days ( SFD ) and Quality of Life ( QoL ) ) in patients with Seasonal Allergic Rhinitis ( SAR ) being treated with fluticasone furoate ( FF ) , mometasone furoate ( MF ) or fluticasone propionate ( FP ) . Methods In a cross-sectional , non-interventional , cohort analysis , primary care physicians and allergy specialists in France , Germany , and Spain were recruited via telephone interviews . Each physician prospect ively recruited 4 SAR patients - 2 receiving FF , 1 receiving MF and 1 receiving FP - during June 2009 . Patients answered questions on symptoms and completed question naires on QoL ( mini-rhinoconjunctivitis Quality of Life Question naire , RQLQ ) and burden of illness ( Pittsburgh Sleep Quality Index ) . Results A total of 540 patients were recruited during June 2009 . 88 patients were subsequently found to be ineligible and excluded from the analyses . In the 4 weeks prior to assessment , patients reported a mean of 14.58 ( ±8.42 ) SFD . Patients receiving FF had more SFD ( mean 15.45 ±8.29 ) than patients receiving MF ( adjusted mean difference -1.22 , 95 % Confidence Interval ( CI ) [ -3.16 to 0.72 ] , p=0.434 ) or FP ( adjusted mean difference -1.95 , 95 % CI [ -3.87 to -0.03 ] , p=0.092 ) , although statistical significance was not achieved . The mean RQLQ score was 1.54 ( ±1.06 ) . Patients receiving FF had a better quality of life in the previous week ( mini-RQLQ score : mean 1.42 , ±1.04 ) than patients receiving MF ( adjusted mean difference 0.28 , 95 % CI [ 0.03 to 0.52 ] , p=0.052 ) or FP ( adjusted mean difference 0.18 , 95 % CI [ -0.05 to 0.41 ] , p=0.244 ) . Again , none of these results achieved statistical significance . Conclusions At the height of the allergy season , patients with SAR suffer symptoms approximately 50 % of the time , and report an impact on their QoL. No significant differences were observed between FF , FP and MF related to SFD or QoL.Trial registration Clinical Trials.gov identifier : Background One fourth of the adult population in Europe suffer from respiratory allergy . Subcutaneous-allergen-specific-immunotherapy ( SCIT ) has long-term disease modifying effect on disease specific Health-Related Quality of Life ( HRQoL ) . The purpose of this study was to assess the effect of SCIT on alternative disease outcomes in patients with grass-pollen and /or house dust mite induced allergic rhino-conjunctivitis and /or an asthma diagnosis . Focus was on expressing outcomes in terms of generic quality of life ( Quality -Adjusted-Life-Years ( QALY ) ) and reductions in sick days . Methods The study was a multi-centre study with prospect i ve follow-up . 248 patients were initiated on SCIT . The disease specific Rhino-conjunctivitis Quality of Life Question naire ( RQLQ ) and two generic ( HRQoL ) instruments 15D and EQ-5D were used at baseline and at follow-up . The outcome measures included change in ; disease severity , RQLQ-scores , number of days with symptoms- and number of sick days per year and finally changes in generic HRQoL and thus , QALY . Disease severity was assessed by specialist doctors ; severity of rhino-conjunctivitis was classified according to the Allergic Rhinitis and its Impact on Asthma ( ARIA ) and asthma severity according to the Global Initiative for Asthma ( GINA guideline ) . The remaining outcome measures were assessed by the patients in question naires at baseline and at follow-up . An intension to treat approach was applied . For missing items imputation of sample mean base-line values or follow-up values were used after specified criteria . The effect of SCIT on rhino-conjunctivitis and /or asthma diagnoses was analysed at follow-up using three logistic regression models . Results The disease severity showed significantly improved disease control . Mean RQLQ-score was reduced from 3.02 at baseline to 2.00 at follow-up . Average annual days with symptoms were reduced from 189 to 145 days whilst annual sick days were reduced from 3.7 to 1.2 days . The 15D-score increased from 0.83 to 0.86 and the EQ-5D-score from 0.70 to 0.77 , which indicated an annual gain per patient of 0.03 - 0.06 QALY . Conclusions Allergic patients suffering from rhino-conjunctivitis alone or rhino-conjunctivitis and asthma experience significantly increased HRQoL and they gain 0.03 - 0.06 QALY , when treated with SCIT for one year . Trial registration The study was registered at Clinical Trials.gov with the identifier : NCT01486498 OBJECTIVE To investigate the health and monetary consequences of treating allergy with specific immunotherapy ( SIT ) compared with symptomatic treatment/st and ard care among patients with grass pollen or mite allergy . METHODS We performed an economic analysis based on 253 grass- and /or mite allergic patients who started SIT from 1.1.1996 to 1.1.2002 at the Allergy Unit , Aarhus University Hospital and at a specialist practice in Aarhus . Relevant data were collected before , during and after SIT treatment from the national health service based on each patient 's personal identification number and medical records and from a specifically design ed question naire . A cost-benefit analysis including direct and indirect costs before , during and after SIT was performed . In addition direct costs were related to the clinical effect ( improvement in well-being ) in the form of a cost-effectiveness analysis . RESULTS The direct cost per patient/year before SIT ( equivalent to st and ard care ) was DKK 2,580 . The investment in SIT was DKK 27,545 ( in present values ) per patient over a 4-year period . After SIT the cost was reduced to DKK 1,072 per patient/year . In the long term , prospect i ve introduction of SIT incurred additional present-value direct costs of DKK 13,676 per patient treated and DKK 2,784 per patient/year of improved well-being . However , when indirect costs were included in the economic evaluation SIT was shown to be net beneficial . CONCLUSION This study reveals that SIT is associated with initial re source investments and subsequent re source savings in the long term compared with st and ard care . When all consequences are measured in monetary terms , and assuming that sick days are associated with a loss of productivity , this analysis suggests that SIT increases societal welfare . This conclusion also holds if there is no loss of productivity OBJECTIVE The objective of this study was to develop empirical algorithms that estimate health-state utility values from disease-specific quality -of-life scores in individuals with migraine . METHODS Data from a cross-sectional , multicountry study were used . Individuals with episodic and chronic migraine were r and omly assigned to training or validation sample s. Spearman 's correlation coefficients between paired EuroQol five-dimensional ( EQ-5D ) question naire utility values and both Headache Impact Test ( HIT-6 ) scores and Migraine-Specific Quality -of-Life Question naire version 2.1 ( MSQ ) domain scores ( role restrictive , role preventive , and emotional function ) were examined . Regression models were constructed to estimate EQ-5D question naire utility values from the HIT-6 score or the MSQ domain scores . Preferred algorithms were confirmed in the validation sample s. RESULTS In episodic migraine , the preferred HIT-6 and MSQ algorithms explained 22 % and 25 % of the variance ( R(2 ) ) in the training sample s , respectively , and had similar prediction errors ( root mean square errors of 0.30 ) . In chronic migraine , the preferred HIT-6 and MSQ algorithms explained 36 % and 45 % of the variance in the training sample s , respectively , and had similar prediction errors ( root mean square errors 0.31 and 0.29 ) . In episodic and chronic migraine , no statistically significant differences were observed between the mean observed and the mean estimated EQ-5D question naire utility values for the preferred HIT-6 and MSQ algorithms in the validation sample s. CONCLUSIONS The relationship between the EQ-5D question naire and the HIT-6 or the MSQ is adequate to use regression equations to estimate EQ-5D question naire utility values . The preferred HIT-6 and MSQ algorithms will be useful in estimating health-state utilities in migraine trials in which no preference-based measure is present BACKGROUND Quality of life ( QOL ) is an important outcome in asthma and seasonal allergic rhinitis ( SAR ) , and its determinants are imperfectly understood . More specifically , the influence of sociodemographic factors on QOL in patients with SAR has been so far little investigated . OBJECTIVE To examine the changes of QOL during the pollen season in patients with isolated SAR or SAR associated with asthma . METHODS A prospect i ve cohort study was conducted in southern France . Out patients aged 18 to 60 years and regularly treated by respiratory physicians for SAR ( with or without associated asthma ) were identified . Patients were recruited before the grass or ragweed pollination period . At peak pollination , patients completed the French versions of the Mini Rhino-conjunctivitis Quality of Life Question naire ( mini-RQLQ ) and the 12-item Short-Form Health Survey ( SF-12 ) physical component summary ( PCS ) and mental component summary ( MCS ) . RESULTS A total of 135 patients was included , 83 with isolated SAR and 52 with associated asthma ( mean age , 35.4 years ; SD , 10.6 years ; 56 % female ) . At pollen peak , QOL scores were lower in women for all instruments , with significant effects on SF-12 MCS and PCS scores in multivariate analyses . Likewise , a university-level education was an independent predictor of higher SF-12 PCS and MCS scores . Patients who lived in rural areas had significantly poorer QOL at pollen peak , as measured by the mini-RQLQ ( P = .002 ) and SF-12 PCS ( P = .008 ) . No influence of age , presence of an animal at home , or smoking status could be identified on any QOL scores . CONCLUSIONS Being a woman , living in the countryside , and having a lower education level were all independent predictors of poorer QOL of SAR patients . These factors must be taken into account when interpreting QOL of patients with SAR . Further studies are needed to confirm these results The objective of this study was to develop and test a health‐related quality of life question naire for clinical trials in rhinoconjunctivitis . The Rhinoconjunctivitis Quality of Life Question naire ( RQLQ ) was developed by asking patients to identify areas of their lives affected by rhinoconjunctivitis . The result ant RQLQ was tested for reproducibility , responsiveness and validity in a r and omized , double‐blind trial of regular versus ‘ as required ’ aqueous beclomethasone dipropionate ( BDP ) nasal spray in ragweed pollen‐induced rhinoconjunctivitis . Eighty‐five patients from previous rhinoconjunctivitis studies participated in the developmental survey . Sixty ragweed‐sensitive patients , from previous trials and media notices , were enrolled in the clinical trial . Aqueous BDP ( 800 μg ) nasal spray was administered regularly or ‘ as required ’ throughout the ragweed pollen season . The survey revealed that , in addition to local symptoms of rhinoconjunctivitis , patients experienced impairment of quality of life through systemic symptoms , sleep disturbance , practical problems , activity limitations and emotional problems . The RQLQ includes 28 questions related to these dimensions . Repeated administration of the RQLQ demonstrated good reproducibility . During the clinical trial , the RQLQ proved responsive in its ability to distinguish between regular and ‘ as required ’ medication use . Validity was shown by moderate to strong relations between changes in symptom diary scores and changes in RQLQ scores . In conclusion the RQLQ is likely to prove useful as a measure of health‐related quality of life in clinical trials in both rhinoconjunctivitis and rhinitis BACKGROUND Persistent allergic rhinitis often impairs quality of life . OBJECTIVE We assessed the extent to which treating persistent allergic rhinitis with montelukast , desloratadine , and levocetirizine alone or in combination improved quality of life . METHODS A 32-week r and omized , double-blind , placebo-controlled , crossover study was performed in 2 arms : 20 patients received montelukast 10 mg/d and /or desloratadine 5 mg/d or placebo ; 20 patients received montelukast 10 mg/d and /or levocetirizine 5 mg/d or placebo . The treatment periods were separated by 2-week washout periods . Quality of life was assessed on the day before starting treatment and on the last day of each treatment period using the Rhinoconjunctivitis Quality of Life Question naire . Sleep problems were also assessed . RESULTS In the desloratadine plus montelukast arm , the mean ( SEM ) quality of life score before treatment was 3.1 ( 0.41 ) . After placebo , this score was 2.16 ( 0.43 ) , after desloratadine it was 1.79 ( 0.38 ) , after montelukast it was 1.48 ( 0.37 ) , and after montelukast plus desloratadine it was 1.59 ( 0.37 ) . In the montelukast plus levocetirizine arm , the mean quality of life score before treatment was 2.58 ( 0.49 ) . After placebo it was 1.78 ( 0.46 ) , after levocetirizine it was 1.38 ( 0.42 ) , after montelukast it was 1.36 ( 0.37 ) , and after montelukast plus levocetirizine it was 1.26 ( 0.39 ) . CONCLUSIONS Placebo , montelukast , desloratadine and levocetirizine significantly improved quality of life . Combining montelukast with either levocetirizine or desloratadine gave additional benefits in comparison to each agent alone and could be considered for patients whose quality of life is impaired by persistent allergic rhinitis BACKGROUND Allergic Rhinitis and its Impact on Asthma in collaboration with the World Health Organization initiative reclassified allergic rhinitis , like asthma , by duration and severity . The Xyzal in Persistent Rhinitis Trial is the first large , long-term clinical trial study ing patients with persistent rhinitis as defined by Allergic Rhinitis and its Impact on Asthma . OBJECTIVES Two primary objectives were defined : comparison of the Rhinoconjunctivitis Quality of Life Question naire overall score and Total 5 Symptoms Score ( rhinorrhea , sneezing , nasal congestion , and nasal and ocular pruritus ) over a period of 4 weeks between levocetirizine 5 mg and placebo . Secondary endpoints included similar evaluations at 1 week and 3 , 4.5 , and 6 months , summary scores for a general health status question naire ( Medical Outcomes Survey Short Form 36 ) , a pharmacoeconomic assessment , comorbidities , and a safety evaluation . METHODS The Xyzal in Persistent Rhinitis Trial was a 6-month double-blind , placebo-controlled , multicenter , multinational trial in 551 patients . Adults with persistent rhinitis sensitized to both grass pollen and house dust mite were r and omized to receive levocetirizine 5 mg/d or placebo . RESULTS A total of 421 patients completed the full study . Levocetirizine significantly improved both the Rhinoconjunctivitis Quality of Life Question naire overall score and the Total 5 Symptoms Score from week 1 to 6 months ( all P values < .001 ) . Medical Outcomes Survey Short Form 36 summary scores were also improved in the levocetirizine group compared with the placebo group . Treatment cessation because of lack of effect , comorbidities , and overall costs of disease , and comorbidities per working patient per month ( 160.27 vs 108.18 ) were lower in the levocetirizine group . CONCLUSION Levocetirizine was shown to improve quality of life and symptoms and to decrease the overall costs of the disease over the 6-month treatment period BACKGROUND Allergic rhinitis is a chronic respiratory disorder with a detrimental impact on health-related quality of life ( HRQOL ) and health status . Enhancement and maintenance of patient function and well-being are therefore considered as essential . OBJECTIVE To determine whether long-term treatment with levocetirizine 5 mg improves HRQOL and health status in persistent allergic rhinitis ( PER ) patients assessed with RQLQ and SF-36 scales over a 6-month period . METHODS The Xyzal in PER Trial ( XPERT ) was a multi-center , double-blind , parallel-group study . A total of 551 patients were r and omized to receive levocetirizine 5 mg or placebo once daily for 6 months and assessed for symptoms , HRQOL ( Rhinoconjunctivitis Quality of Life Question naire : RQLQ ) and health status ( SF-36 ) . Sensitivity of the RQLQ and SF-36 to disease severity was tested to ensure their suitability for use in PER patients . Treatment effect was assessed by means of repeated measures analyses . RESULTS Over the 6-month treatment period , levocetirizine showed statistically significant improvements over placebo in HRQOL ( P < 0.001 for all RQLQ domains and overall scores ) and health status ( P < or = 0.004 for SF-36 physical and mental summary scores ; P < 0.05 for all SF-36 scales ) . The relative improvement of levocetirizine over placebo exceeded the predefined clinical ly meaningful threshold of 30 % for all RQLQ scores and the improvement from baseline was 3 times the established MID for RQLQ . CONCLUSION The RQLQ and SF-36 could be used to measure HRQOL and health status in PER patients . Long-term treatment with levocetirizine provides sustained improvement of HRQOL and reduces disease burden in PER patients Background : Allergic rhinitis was recently classified by the ARIA guidelines as persistent or intermittent . Levocetirizine was shown to improve symptoms and health‐related quality of life of patients with persistent allergic rhinitis in the XPERTTM study , a 6‐month r and omized double blind placebo‐controlled trial Allergic rhinitis is a global illness with a well-recognised impact on quality of life and work performance . Comparatively little is known about the extent of its economic impact on society . The TOTALL study estimates the total cost of allergic rhinitis using a sample representing the entire Swedish population of working age . A question naire focused on allergic rhinitis was mailed out to a r and om population of Swedish residents , aged 18–65 years . Health-care contacts , medications , absenteeism ( absence from work ) and presenteeism ( reduced working capacity at work ) were assessed , and the direct and indirect costs of allergic rhinitis were calculated . Medication use was evaluated in relation to the ARIA guidelines . In all , 3,501 of 8,001 ( 44 % ) answered the question naire , and 855 ( 24 % ) of these reported allergic rhinitis . The mean annual direct and indirect costs because of allergic rhinitis were € 210.3 and € 750.8 , respectively , result ing in a total cost of € 961.1 per individual/year . Presenteeism represented 70 % of the total cost . Antihistamines appear to be used in excess in relation to topical steroids , and the use of nasal decongestants was alarmingly high . The total cost of allergic rhinitis in Sweden , with a population of 9.5 million , was estimated at € 1.3 billion annually . These unexpectedly high costs could be related to the high prevalence of disease , in combination with the previously often underestimated indirect costs . Improved adherence to guidelines might ease the economic burden on society Abstract Allergic rhinitis is considered to be a major health problem that impairs quality of life . A possible relationship with psychological stress may exist . The aim of this study is to verify the relationship between persistent allergic rhinitis ( PAR ) and psychological stress aim ing to improve treatment and thereby quality of life ( QOL ) of patients . Patients with PAR ( 166 ) were diagnosed then analyzed using the Kessler Psychological Distress Scale . Patients with allergic rhinitis and who were positive on the Kessler scale ( 122 ) were r and omly divided equally into a control group which received levocetirizine and a study group which received levocetirizine and imipramine . Nasal symptom assessment and QOL assessment were performed in all patients after treatment . Of the 166 patients with PAR , 122 ( 73.5 % ) were positive on the Kessler Psychological Distress Scale . There was a marked improvement in the study group compared with the control group as regards nasal symptoms with better QOL in the study group ( 6.93 ) compared with the control group ( 2.13 ) . Psychological stress has a strong impact on persistent allergic rhinitis . When stress is controlled by a combined treatment of imipramine and levocetirizine , allergic rhinitis symptoms improved and a better QOL was obtained . Level of evidence : 3b OBJECTIVES This study aims to compare the effectiveness of desloratadine monotherapy and desloratadine plus montelukast combination therapy on quality of life in patients with persistent allergic rhinitis . PATIENTS AND METHODS This study consists of 40 patients ( 28 females , 12 males , mean age 29.8 years ; range 17 to 44 years ) referred to ear , nose , and throat outpatient clinic between May 2010 and September 2010 . A six-week r and omized , double-blind , cross-sectional study was performed in two arms : In group 1 , 20 patients received desloratadine ( 5 mg/d ) alone ; in group 2 , 20 patients received desloratadine ( 5 mg ) plus montelukast ( 10 mg ) combination therapy . Quality of life was assessed on the day before starting treatment and on the last day of each treatment period using the Rhinoconjunctivitis Quality of Life Question naire and Nighttime Symptom Scores . RESULTS In group 1 , the mean quality of life scores before and after treatment were 3.17 and 2.43 , respectively . In group 2 , the mean quality of life scores before and after treatment were 2.94 and 1.73 , respectively . CONCLUSION Desloratadine plus montelukast combination therapy may have a positive impact on quality of life , sleep symptoms in particular Background In clinical trials , patients have expressed greater satisfaction with inhaled human insulin ( EXUBERA ® , Pfizer ) than with injectable insulin . No studies to date have attempted to quantify the strength of preferences for these alternative routes of administration . Objective To elicit health state preference values from people with diabetes mellitus for treatment with inhaled human insulin compared with injectable insulin . Study design A patient preference study . Methods Written descriptions were developed for five clinical scenarios : two for type 1 diabetes and three for type 2 diabetes . Each scenario required adjustment or initiation of insulin treatment because of poor glycaemic control . Two alternative insulin regimens were described for each scenario : injectable-only or inhaled human insulin to replace or reduce the number of daily injections . Equal efficacy was assumed within each of these scenario pairs . A total of 344 UK adults ( 66 % male ) , 132 ( mean age 49 years ) with type 1 diabetes and 212 ( mean age 63 years ) with type 2 diabetes , rated scenario pairs corresponding to their own type of diabetes and rated their own health by time trade-off ( TTO ) , by correspondence with EQ-5D health descriptions and on the EQ-5D visual analogue scale . Respondents stated their preference for , or indifference between , the injection-only or inhalation variant comprising each scenario pair . TTO utilities and EQ-5D utilities by UK community tariff were compared within each scenario pair , for the total sample rating , each scenario pair , and by subgroups of stated preference for each variant . Results A majority , ranging from 63 % to 81 % across the scenarios , preferred inhalation . Mean differences in TTO scores were 0.074 , 0.076 , 0.088 , 0.053 and 0.043 for the five scenarios , respectively ( p < 0.005 for all ) . Mean EQ-5D differences were 0.043 , 0.029 , 0.037 , 0.020 and 0.021 for the five scenarios , respectively ( p < 0.05 for scenarios 1 and 3 ) , driven mainly by differences on the pain/discomfort dimension of the EQ-5D . Differences in favour of inhalation among those preferring inhalation , were greater than differences in favour of injections among those preferring injections . Mean self-rated health was similar between respondents with type 1 and type 2 diabetes , at 0.83 ( TTO ) and 0.75 ( EQ-5D ) . The TTO was more sensitive than EQ-5D . Self-rated health by EQ-5D compared closely with reported values from the UK Prospect i ve Diabetes Study ( UKPDS ) . Conclusions This study highlights the utility differences that people with diabetes perceive between the prospect of inhaled and injected routes of insulin administration , even under the assumption of no difference in efficacy . These differences are magnified when the comparison in utility scores is between the majority who prefer the inhaled route and the minority who prefer the injectable route BACKGROUND Quality of life ( QOL ) is an important issue in allergic rhinitis and has been evaluated in a number of studies that have shown how it is impaired in untreated patients and improved by effective treatment . However , there are no data concerning QOL after sublingual immunotherapy ( SLIT ) in polysensitized patients . OBJECTIVE To evaluate the effect , in real-life clinical practice , of SLIT on QOL in a population of polysensitized patients with allergic rhinitis . METHODS We prospect ively evaluated 167 consecutively enrolled polysensitized patients with allergic rhinitis . QOL was measured in all cases with the Rhinoconjunctivitis Quality of Life Question naire at baseline and after 1 year of SLIT ( performed in approximately 70 % of cases using single allergen extracts provided by the same manufacturer ) . RESULTS The most frequent causes of sensitization were grass pollen , Parietaria , and house dust mites . The mean number of sensitizations per patient was 3.65 . SLIT was performed with 1 extract in 123 patients ( 73.6 % ) , with 2 extracts in 31 patients ( 18.6 % ) , and with more than 2 extracts in 13 patients ( 7.8 % ) . The mean values of all the QOL items improved significantly ( P < .01 in all cases ) , with the following reductions noted : activities , 3.96 to 2.89 ; sleep , 2.07 to 1.56 ; general problems , 2.16 to 1.5 ; practical problems , 3.69 to 2.58 ; nasal symptoms , 3.57 to 2.50 ; eye symptoms , 2.92 to 1.83 ; and emotional aspects , 2.2 to 1.44 . CONCLUSIONS This study provides evidence that QOL can be improved in polysensitized patients treated with SLIT , and that the use of just 1 or 2 allergen extracts seems to be sufficient and effective in terms of improving QOL BACKGROUND Despite an increasing recognition that both asthma and allergic rhinitis are serious health disorders in Thail and , their combined effects on patients ' quality of life in the Thai population has not been reported . OBJECTIVE The study aim ed to evaluate the impacts of allergic rhinitis and asthma on the quality of life of young adolescents in Thail and . METHODS A total of 1,440 pupils , aged 12 - 14 years , were r and omly recruited from 4 schools located in Bangkok and Pathum Thani Province . Allergic rhinitis and asthmatic symptoms were identified by the International Study of Asthma and Allergies in Childhood ( ISAAC ) written question naire . The Pediatric Quality of Life Inventory ( PedsQL ) question naire was used to evaluate their quality of life . RESULTS There were 1,230 completed question naires for analysis . The prevalence of allergic rhinitis alone , asthma alone and diseases co-occurrence was 32.8 % , 7.2 % , and 12.7 % respectively . Pupils with respiratory allergy had significantly lower PedsQL mean scores than healthy pupils , for all dimensions ( p < 0.006 ) . The greatest reduction of the PedsQL mean score was for emotional functioning . Among pupils with allergic rhinitis , those who were also affected with asthma had significantly lower mean scores , for all quality of life domains ( all p < 0.001 ) . Compared to allergic rhinitis , asthma significantly reduced PedsQL mean scores in almost all domains ( p < 0.001 ) , except for physical health . CONCLUSIONS Allergic rhinitis and asthma have a significant influence on the quality of life in young Thai adolescents , in particular regarding emotional functioning . Asthma has stronger negative effects on life quality than allergic rhinitis , especially regarding psychosocial health Background : Allergic rhinitis ( AR ) impairs quality of life ( QoL ) , sleep and work . The Allergic Rhinitis and its Impact on Asthma ( ARIA ) classification is widely used , but the impact of the different symptoms on QoL is not clear . Objective : To describe characteristics of patients consulting in primary care for AR and to study the impact of AR symptoms and the ARIA classes on QoL. Methods : A multicenter prospect i ve observational cross-sectional study assessed the visual analogue scale ( VAS ) in the management of AR in 990 patients consulting general practitioners for AR . Patients were classified according to the four classes of ARIA . VAS , Rhinoconjunctivitis Quality of Life Question naire ( RQLQ ) and total symptom score ( TSS ) for nasal and non-nasal symptoms were evaluated . VAS and TSS measures were compared with RQLQ . Results : Mild intermittent rhinitis was diagnosed in 20 % of patients , mild persistent rhinitis in 17 % , moderate/severe intermittent rhinitis in 15 % and moderate/severe persistent rhinitis in 48 % . The presence of treatments did not affect VAS levels . Both severity and duration of rhinitis had an impact on QoL and VAS levels . Ocular symptoms ( OR : 2.78 , 95 % CI : 1.965–3.939 ) including eyelid edema ( OR : 2.07 , 95 % CI : 1.274–3.360 ) and asthenia ( OR : 2.73 , 95 % CI : 1.922–3.877 ) had more impact on RQLQ than nasal obstruction ( OR : 1.61 , 95 % CI : 1.078–2.405 ) and nasal pruritus ( OR 1.45 , 95 % CI : 1.028–2.042 ) . Sneezing and rhinorrhea did not impact RQLQ . Conclusions : This study confirmed that ocular symptoms and , to a lesser degree , nasal obstruction and pruritus have a significant impact on BACKGROUND It has long been assumed that allergic rhinitis leads to daytime sleepiness and a deterioration of nocturnal sleep , yet systematic studies have only been rarely conducted in this field . OBJECTIVE The aim of the present study was to investigate the effects of seasonal allergic rhinitis on subjective and objective sleep patterns , quality of life , and daytime sleepiness in otherwise healthy subjects in comparison with nonallergic volunteers . METHODS Twenty-five patients with seasonal allergic rhinitis and 25 healthy volunteers were enrolled in this prospect i ve , controlled clinical trial . Daytime sleepiness and quality of life were assessed with the help of question naires ( Epworth Sleepiness Scale , SF-36 ) ; 2 consecutive nights of fully attended polysomnography were performed before and during the pollen season of 2002 . RESULTS Statistically significant differences between groups were found in respect to changes in daytime sleepiness and selected parameters of quality of life . Impairment of daytime sleepiness and quality of life were related to the severity of the disease . Statistically significant differences were also found for selected parameters of the sleep studies , although the changes were only minimal , and all values were within normal ranges . CONCLUSION Seasonal allergic rhinitis leads to increased daytime sleepiness , as well as to an impairment of quality of life , depending on the severity of the disease . Objective measurements revealed a statistically significant influence of seasonal allergic rhinitis on selected sleep parameters , but changes were not of clinical relevance . Daytime sleepiness seems to be related to the condition itself rather than to an impairment of nocturnal sleep OBJECTIVE This study investigated improvements in quality of life associated with eight weeks of montelukast and /or intranasal steroid treatment for moderate to severe allergic rhinitis . METHODS A single-centre , prospect i ve , r and omised , double-blind , placebo-controlled study was carried out . Assessment s were made using the Rhinoconjunctivitis Quality of Life Question naire and symptom scales . RESULTS A total of 128 patients ( aged 13 - 51 years ) were r and omly assigned to one of two groups . In the montelukast group , patients were treated with montelukast tablets and fluticasone propionate nasal spray ( n = 64 ) . In the placebo group , treatment comprised a placebo and fluticasone propionate . The results showed significant improvements in symptom scores and quality of life scores for both groups after one month and two months of treatment , compared with baseline values ; these improvements were significantly greater for the montelukast group compared with the placebo group . The mean number of loratadine tablets taken by each patient during the study period was only 0.73 for the montelukast group compared with 9 for the placebo group . CONCLUSION The combination of montelukast tablets and fluticasone propionate nasal spray improved symptom control and overall quality of life for moderate to severe allergic rhinitis patients In a recent placebo‐controlled study we demonstrated that capsaicin is an efficacious substance in the treatment of non‐allergic non‐infectious rhinitis . In this study the therapeutic effect lasted more than 9 months . This effect was not based on modulation of inflammation BACKGROUND The inhalation of Salsola kali pollen is a common cause of respiratory diseases in Europe and North America . OBJECTIVE To evaluate the efficacy and safety of a depigmented and glutaraldehyde-polymerized therapeutic vaccine of S kali . METHODS The trial was r and omized , double-blind , and placebo-controlled using a rush protocol in the build-up phase . Sixty patients with rhinoconjunctivitis ( 19 also had mild asthma ) were r and omly allocated to receive either active treatment ( polymerized extract ) or placebo . The final distribution was 41 patients in the active and 19 in the placebo group . Side effects were registered . Symptom and medication scores and the number of days free of symptoms during the pollen season were assessed to evaluate the clinical efficacy . A Rhinoconjunctivitis Quality of Life Question naire was completed in the previous pollen season ( before treatment ) and during the pollen season 1 year later ( in the trial ) . Dose-response skin tests were performed at baseline and at the end of the trial . RESULTS There was a significant difference ( P < .05 ) in symptom and medication scores between both groups during the pollen season , with the active group the one that had fewer symptoms and lower intake of medication . The number of days without symptoms was higher in the active group ( P < .05 ) . This group also had a significant improvement in the Rhinoconjunctivitis Quality of Life Question naire and a reduction in skin sensitivity . No moderate or severe systemic reactions were registered . CONCLUSION Immunotherapy with this modified vaccine of S kali pollen is safe and efficacious to treat patients clinical ly sensitive to this pollen . CLINICAL IMPLICATION S Patients allergic to S kali ( Russian thistle ) can be successfully treated with immunotherapy to improve symptoms of allergic rhinitis and asthma , reduce medication use , and improve quality of life parameters From 1200 households selected at r and om , 2114 question naires were returned from individuals over 14 years old . They reported that in the previous year the prevalence of ' symptoms of nasal obstruction every day for more than 14 consecutive days ' was 16.9 % ; 19.8 % had had a ' runny nose ' ; 7.1 % reported sneezing bouts ; and 19.6 % had hay fever during the same period . Also , 13.7 % had had rhinosinusitis in the previous year using the criterion of ' two out of three symptoms of congestion , rhinorrhoea and sneezing for more than 1 h per day for a period in excess of 2 weeks ' . The prevalence of perennial symptoms in individuals who did not have hay fever was 8.6 % . Over the previous 2 years 18.2 % of all respondents had visited their General Practitioner and 0.2 % had visited a hospital as a result of their hay fever . Individuals who responded as having hay fever were significantly more likely to have worked in an environment with a lot of dust in the last 2 years than asymptomatic respondents ( chi 2 , P = 0.002 ) , although fume exposure was not found to be a significant risk factor ( P = 0.0681 ) . Individuals with perennial symptoms were no more likely to have been working in a dusty or smoky environment . In those with either seasonal or perennial symptoms there was no significant effect of either social class or manual/non-manual occupation Background Rhinoconjunctivitis due to birch pollen sensitization is common in Northern Europe . A depigmented polymerized birch pollen extract – Depigoid ® has been developed for immunotherapy |
13,875 | 19,648,153 | CONCLUSIONS Overall , the available evidence did not support any benefit from pre-hospital intubation and mechanical ventilation after TBI . | BACKGROUND We review ed the current evidence on the benefit and harm of pre-hospital tracheal intubation and mechanical ventilation after traumatic brain injury ( TBI ) . | BACKGROUND Although early intubation to prevent the mortality that accompanies hypoxia is considered the st and ard of care for severe traumatic brain injury ( TBI ) , the efficacy of this approach remains unproven . METHODS Patients with moderate to severe TBI ( Head/Neck Abbreviated Injury Scale [ AIS ] score 3 + ) were identified from our county trauma registry . Logistic regression was used to explore the impact of prehospital intubation on outcome , controlling for age , gender , mechanism , Glasgow Coma Scale score , Head/Neck AIS score , Injury Severity Score , and hypotension . Neural network analysis was performed to identify patients predicted to benefit from prehospital intubation . RESULTS A total of 13,625 patients from five trauma centers were included ; overall mortality was 22.9 % , and 19.3 % underwent prehospital intubation . Logistic regression revealed an increase in mortality with prehospital intubation ( odds ratio , 0.36 ; 95 % confidence interval , 0.32 - 0.42 ; p < 0.001 ) . This was true for all patients , for those with severe TBI ( Head/Neck AIS score 4 + and /or Glasgow Coma Scale score of 3 - 8 ) , and with exclusion of patients transported by aeromedical crews . Patients intubated in the field versus the emergency department had worse outcomes . Neural network analysis identified a subgroup of patients with more significant injuries as potentially benefiting from prehospital intubation . CONCLUSION Prehospital intubation is associated with a decrease in survival among patients with moderate-to-severe TBI . More critically injured patients may benefit from prehospital intubation but may be difficult to identify prospect ively BACKGROUND Prehospital intubation and airway control is routinely performed by paramedics in critically injured patients . Despite the advantages provided by this procedure , numerous potential risks exist when this is performed in the field . We review ed the outcome of patients with severe head injury , to determine whether prehospital intubation is associated with an improved outcome . METHODS A retrospective review of registry data of patients admitted to an urban trauma center with severe head injury ( field Glasgow Coma Scale score of < or = 8 and head Abbreviated Injury Scale score of > or =3 ) was performed . Patients were stratified by methods of airway control performed by prehospital personnel : not intubated , intubated , or unsuccessful intubation . Mortality was determined for each group . To control for significant variables between these population s , matching and multivariate analysis were performed . RESULTS Patients requiring prehospital intubation or in whom intubation was attempted had an increased mortality ( 81 % and 77 % , respectively ) when compared with nonintubated patients ( 43 % ) . The mortality for patients who had prehospital intubation performed did not demonstrate an improved survival using matching . In fact , intubated patients had a significantly higher relative risk ( RR ) of mortality when compared with nonintubation ( RR = 1.74,p < 0.001 ) and unsuccessful intubation patients ( RR = 1.53 , p = 0.008 ) CONCLUSION For patients with severe head injury , prehospital intubation did not demonstrate an improvement in survival . Further prospect i ve r and omized trials are necessary to confirm these results The value of advanced prehospital life support for patients with severe trauma — for example , endotracheal intubation by ambulance staff — is unclear . Only one r and omised controlled trial was found among 2034 papers in a Cochrane review , concluding that advanced trauma life support by ambulance crews should be initiated only as part of rigorously conducted trials.1 A critical review also failed to show benefit and reported success rates for endotracheal intubation from 57 % to 92%.2 The review question ed whether prehospital staff could master the required skills . These review s focus on paramedic based systems . The helicopter emergency medical services in London is staffed by doctors ; the service studied 486 trauma patients OBJECTIVE To quantify the occurrence of arterial hypotension and arterial oxygen desaturation in a series of patients with head trauma rescued by helicopter . DESIGN Prospect i ve , observational study . MATERIAL S AND METHODS Arterial HbO2 was measured before tracheal intubation at the accident scene in 49 consecutive patients with head injuries . Arterial pressure was measured using a sphygmomanometer . MAIN RESULTS Mean arterial saturation was 81 % ( SD 24.24 ) ; mean arterial systolic pressure was 112 mm Hg ( SD 37.25 ) . Airway obstruction was detected in 22 cases . Twenty-seven patients showed an arterial saturation lower than 90 % on the scene , and 12 had a systolic arterial pressure of less than 100 mm Hg . The outcome was significantly worse in cases of hypotension , desaturation , or both . CONCLUSIONS Hypoxemia and shock are frequent findings on patients at the accident scene . Hypoxemia is more frequently detected and promptly corrected , white arterial hypotension is more difficult to control . Both insults may have a significant impact on outcome CONTEXT Endotracheal intubation ( ETI ) is widely used for airway management of children in the out-of-hospital setting , despite a lack of controlled trials demonstrating a positive effect on survival or neurological outcome . OBJECTIVE To compare the survival and neurological outcomes of pediatric patients treated with bag-valve-mask ventilation ( BVM ) with those of patients treated with BVM followed by ETI . DESIGN Controlled clinical trial , in which patients were assigned to interventions by calendar day from March 15 , 1994 , through January 1 , 1997 . SETTING Two large , urban , rapid-transport emergency medical services ( EMS ) systems . PARTICIPANTS A total of 830 consecutive patients aged 12 years or younger or estimated to weigh less than 40 kg who required airway management ; 820 were available for follow-up . INTERVENTIONS Patients were assigned to receive either BVM ( odd days ; n = 410 ) or BVM followed by ETI ( even days ; n = 420 ) . MAIN OUTCOME MEASURES Survival to hospital discharge and neurological status at discharge from an acute care hospital compared by treatment group . RESULTS There was no significant difference in survival between the BVM group ( 123/404 [ 30 % ] ) and the ETI group ( 110/416 [ 26 % ] ) ( odds ratio [ OR ] , 0.82 ; 95 % confidence interval [ CI ] , 0.61 - 1.11 ) or in the rate of achieving a good neurological outcome ( BVM , 92/404 [ 23 % ] vs ETI , 85/416 [ 20 % ] ) ( OR , 0.87 ; 95 % CI , 0.62 - 1.22 ) . CONCLUSION These results indicate that the addition of out-of-hospital ETI to a paramedic scope of practice that already includes BVM did not improve survival or neurological outcome of pediatric patients treated in an urban EMS system As triage and resuscitation protocol s evolve , it is critical to determine the major extracranial variables influencing outcome in the setting of severe head injury . We prospect ively studied the outcome from severe head injury ( GCS score < or = 8) in 717 cases in the Traumatic Coma Data Bank . We investigated the impact on outcome of hypotension ( SBP < 90 mm Hg ) and hypoxia ( Pao2 < or = 60 mm Hg or apnea or cyanosis in the field ) as secondary brain insults , occurring from injury through resuscitation . Hypoxia and hypotension were independently associated with significant increases in morbidity and mortality from severe head injury . Hypotension was profoundly detrimental , occurring in 34.6 % of these patients and associated with a 150 % increase in mortality . The increased morbidity and mortality related to severe trauma to an extracranial organ system appeared primarily attributable to associated hypotension . Improvements in trauma care delivery over the past decade have not markedly altered the adverse influence of hypotension . Hypoxia and hypotension are common and detrimental secondary brain insults . Hypotension , particularly , is a major determinant of outcome from severe head injury . Resuscitation protocol s for brain injured patients should assiduously avoid hypovolemic shock on an absolute basis OBJECTIVE Determine whether prehospital advanced life support ( ALS ) improves the survival of major trauma patients and whether it is associated with longer on-scene times . METHODS A 36-month retrospective study of all major trauma patients who received either prehospital bag-valve-mask ( BVM ) or endotracheal intubation ( ETI ) and were transported by paramedics to our Level I trauma center . Logistic regression analysis determined the association of prehospital ALS with patient survival . RESULTS Of 9,451 major trauma patients , 496 ( 5.3 % ) had either BVM or ETI . Eighty-one percent received BVM , with a mean Injury Severity Score of 29 and a mortality rate of 67 % ; 93 patients ( 19 % ) underwent successful ETI , with a mean Injury Severity Score of 35 and a mortality rate of 93 % . Adjusted survival for patients who had BVM was 5.3 times more likely than for patients who had ETI ( 95 % confidence interval , 2.3 - 14.2 , p = 0.00 ) . Survival among patients who received intravenous fluids was 3.9 times more likely than those who did not ( p = not significant ) . Average on-scene times for patients who had ETI or intravenous fluids were not significantly longer than those who had BVM or no intravenous fluids . CONCLUSION ALS procedures can be performed by paramedics on major trauma patients without prolonging on-scene time , but they do not seem to improve survival BACKGROUND Pre-hospital endotracheal intubation for the purpose of controlled ventilation may prevent secondary brain injury in patients with severe head injury . In view of the limited monitoring devices utilized in the pre-hospital setting , little is known about the ' quality ' of controlled ventilation initiated in the pre-hospital setting . METHODS Included in this prospect i ve study were 122 trauma patients with severe head injury ( abbreviated injury scale score > or = 3 ) . In all cases , the pre-hospital treatment included endotracheal intubation in the field . Upon hospital admission , and maintaining the same ventilation mode and setting initiated in the pre-hospital setting , arterial blood gas sample s were taken . RESULTS ' Optimal ' oxygenation ( PaO2 > 100 mm Hg ) was achieved in 85.2 % and ' adequate ' ventilation ( PaCO2 35 - 45 mm Hg ) in 42.6 % of the patients upon hospital admission . ' Optimal ' oxygenation as well as ' adequate ' ventilation was achieved in 37.7 % of the study population . Hypoxaemia ( PaO2 < 60 mm Hg ) was observed in 2.5 % , hypercapnia ( PaCO2 > 45 mm Hg ) in 16.4 % , and hypocapnia ( PaCO2 < 35 mm Hg ) in 40.9 % of the study patients . The incidence of hypocapnia was significantly more frequent in polytraumatized patients . Hypocapnia as well as hypercapnia was significantly more frequent in patients with associated pulmonary contusion . CONCLUSIONS Endotracheal intubation and controlled ventilation of the lungs initiated in the pre-hospital setting do not guarantee optimal oxygenaton and ventilation in patients with severe head injury STUDY OBJECTIVE We evaluate the ability of paramedic rapid sequence intubation ( RSI ) to facilitate intubation of patients with severe head injuries in an urban out-of-hospital system . METHODS Adult patients with head injuries were prospect ively enrolled over a 1-year period by using the following inclusion criteria : Glasgow Coma Scale score of 3 to 8 , transport time of greater than 10 minutes , and inability to intubate without RSI . Midazolam and succinylcholine were administered before laryngoscopy , and rocuronium was given after tube placement was confirmed by means of capnometry , syringe aspiration , and pulse oximetry . The Combitube was used as a salvage airway device . Outcome measures included intubation success rates , preintubation and postintubation oxygen saturation values , arrival arterial blood gas values , and total out-of-hospital times for patients intubated en route versus on scene . RESULTS Of 114 enrolled patients , 96 ( 84.2 % ) underwent successful endotracheal intubation , and 17 ( 14.9 % ) underwent Combitube intubation , with only 1 ( 0.9 % ) airway failure . There were no unrecognized esophageal intubations . On arrival at the trauma center , median oxygen saturation was 99 % , mean arrival PO2 was 307 mm Hg , and mean arrival PCO2 was 35.8 mm Hg . Total out-of-hospital times were higher when RSI was performed on scene ( 26 versus 13 minutes ) . CONCLUSION Paramedics can use RSI protocol s that include neuromuscular blocking and sedative agents to facilitate intubation of patients with head injuries OBJECTIVE To evaluate the effect of paramedic rapid sequence intubation ( RSI ) on outcome in patients with severe traumatic brain injury . METHODS Adult major trauma victims were prospect ively enrolled over two years using the following inclusion criteria : Glasgow Coma Scale ( GCS ) 3 - 8 , suspected head injury by mechanism or physical examination , transport time > 10 , " and inability to intubate without RSI . Midazolam and succinylcholine were administered before laryngoscopy ; rocuronium was given after tube placement was confirmed using physical examination , capnometry , syringe aspiration , and pulse oximetry . The Combitube was used as a salvage airway device . For this analysis , trial patients were excluded for absence of a head injury ( Head/Neck AIS score < 2 ) , failure to fulfill major trauma outcome study criteria , unsuccessful intubation or Combitube insertion , or death in the field or in the resuscitation suite within 30 " of arrival . Each study patient was h and matched to three nonintubated historical controls from our trauma registry using the following parameters : age , sex , mechanism of injury , trauma center , and AIS score for each body system . Controls were excluded for Head/Neck AIS defined by a c-spine injury or death in the field or in the resuscitation suite within 30 " of arrival . chi 2 , odds ratios , and logistic regression were used to investigate the impact of RSI on the primary outcome measures of mortality and incidence of a " good outcome , " defined as discharge to home , rehabilitation , psychiatric facility , jail , or signing out against medical advice . RESULTS A total of 209 trial patients were h and matched to 627 controls . The groups were similar with regard to all matching parameters , admission vital signs , frequency of specific head injury diagnoses , and incidence of invasive procedures . Mortality was significantly increased in the trial cohort versus controls for all patients ( 33.0 % versus 24.2 % , p < 0.05 ) and in those with Head/Neck AIS scores of 3 or greater ( 41.1 % versus 30.3 % , p < 0.05 ) . The incidence of a " good outcome " was lower in the trial cohort versus controls ( 45.5 % versus 57.9 % , p < 0.01 ) . Factors that may have contributed to the increase in mortality include transient hypoxia , inadvertent hyperventilation , and longer scene times associated with the RSI procedure . CONCLUSION Paramedic RSI protocol s to facilitate intubation of head-injured patients were associated with an increase in mortality and decrease in good outcomes versus matched historical controls OBJECTIVES The aim of this prospect i ve study in the prehospital setting was to compare three different methods for immediate confirmation of tube placement into the trachea in patients with severe head injury : auscultation , capnometry , and capnography . METHODS All adult patients ( > 18 years ) with severe head injury , maxillofacial injury with need of protection of airway , or polytrauma were intubated by an emergency physician in the field . Tube position was initially evaluated by auscultation . Then , capnometry and capnography was performed ( infrared method ) . Emergency physicians evaluated capnogram and partial pressure of end tidal carbon dioxide ( EtCO(2 ) ) in millimetres of mercury . Determination of final tube placement was performed by a second direct visualisation with laryngoscope . Data are mean ( SD ) and percentages . RESULTS There were 81 patients enrolled in this study ( 58 with severe head injury , 6 with maxillofacial trauma , and 17 politraumatised patients ) . At the first attempt eight patients were intubated into the oesophagus . Afterwards endotracheal intubation was undertaken in all without complications . The initial capnometry ( sensitivity 100 % , specificity 100 % ) , capnometry after sixth breath ( sensitivity 100 % , specificity 100 % ) , and capnography after sixth breath ( sensitivity 100 % , specificity 100 % ) were significantly better indicators for tracheal tube placement than auscultation ( sensitivity 94 % , specificity 66 % , p<0.01 ) . CONCLUSION Auscultation alone is not a reliable method to confirm endotracheal tube placement in severely traumatised patients in the prehospital setting . It is necessary to combine auscultation with other methods like capnometry or capnography BACKGROUND Intubation and airway control of injured children is of vital importance , but despite its advantages is associated with meny risks when is performed outside the hospital and by the untrained physicians . Aim of this study was to determine the importance for the survival of the children with craniocerebral injuries , and also for final outcome of treatment . METHODS This study is a clinical , partly prospect i ve , partly retrospective that includes 60 patients ( two groups with 30 patients ) with isolated craniocerebral injures , aged up to 17 years , and with GCS under 8 , that did not require surgical treatment . The first group included patients that were endotracheal intubated , and the other group included patients that were not intubated . RESULTS Theree was no statistically difference between groups regarding the sex , age and GCS . Regarding the endotracheal intubation there was a statistically significant difference , in the first group 86,7 % of the patients were intubated during the prehospital treatment , while 16,7 % of the patients from group II were intubated . A greater percentage of patients from group I underwent controlled ( 66,7 % ) or assisted ( 20 % ) mode of ventilation , and 13,3 % of patients were on spontaneus breathing . CONCLUSION Endotracheal intubation should be performed by an experienced physician with an adequate equipment CONTEXT Head injury is the leading cause of traumatic death in the United States . HYPOTHESIS A set of clinical parameters available soon after injury can be used to accurately predict outcome in patients with severe blunt head trauma . DESIGN Validation cohort study . SETTING Urban level I trauma center . PATIENTS AND METHODS Data from patients with severe blunt head injury , as defined by inability to follow comm and s , were prospect ively entered into a neurosurgical data base and analyzed . The impact on survival of 23 potentially predictive parameters was studied using univariate analysis . Logistic regression models were used to control for confounding factors and to assess interactions between variables , whose significance was determined by univariate analysis . Goodness of fit was calculated with the Hosmer-Lemeshow c statistic . The predictability of the logistic model was evaluated by measuring the area under the receiver operating characteristic curve ( AUC ) . RESULTS Logistic regression analysis revealed that 5 risk factors were independently associated with death . These variables included systemic hypotension in the emergency department , midline shift on computed tomographic scan , intracranial hypertension , and absence of pupillary light reflex . A low Glasgow Coma Scale score and advanced age were found to be highly correlated risk factors that , when combined , were independently associated with mortality . The model showed acceptable goodness of fit , and the AUC was 80.5 % . CONCLUSIONS Systemic hypotension and intracranial hypertension are the only independent risk factors for mortality that can be readily treated during the initial management of patients with severe head injuries . When used together , Glasgow Coma Scale score and age are significant predictors of mortality OBJECTIVES There is an absence of prospect i ve data evaluating the impact of prehospital intubation in adult trauma patients . Our objectives were to determine the outcome of trauma patients intubated in the field who did not have an acutely lethal traumatic brain injury ( death within 48 hours ) compared with patients who were intubated immediately on arrival to the hospital . METHODS Prospect i ve data were collected on 191 consecutive patients admitted to the trauma center with a field Glasgow Coma Scale score < or = 8 and a head Abbreviated Injury Scale score > or = 3 who were either intubated in the field or intubated immediately at admission to the hospital . Patients who died within 48 hours of admission and transfers were excluded from the study . RESULTS Of the 191 patients , 176 ( 92 % ) sustained blunt trauma and 25 ( 8 % ) were victims of penetrating trauma . Seventy-eight ( 41 % ) of the 191 patients were intubated in the field and 113 ( 59 % ) were intubated immediately at admission . There was no significant difference in age , Glasgow Coma Scale score , head Abbreviated Injury Scale score , or Injury Severity Score between the two groups . Patients who were intubated in the field had a significantly higher morbidity ( ventilator days , 14.7 vs. 10.4 ; hospital days , 20.2 vs. 16.7 ; and intensive care unit days , 15.2 vs. 11.7 ) compared with patients intubated on immediate arrival to the hospital and nearly double the mortality ( 23 % vs. 12.4 ) . Field-intubated patients had a 1.5 times greater risk of nosocomial pneumonia compared with hospital-intubated patients . CONCLUSION Prehospital intubation is associated with a significant increase in morbidity and mortality in trauma patients with traumatic brain injury who are admitted to the hospital without an acutely lethal injury . A r and omized , prospect i ve study is warranted to confirm these results HYPOTHESIS A pattern of prehospital care combining advanced life support , physician staffing , and helicopter transport improves the outcome of patients with severe brain injuries , compared with combined exp and ed basic life support , nurse staffing , and ground transport . DESIGN Inception cohort from the data set of a population -based , prospect i ve study on major trauma . SETTING Prehospital and hospital trauma systems of an Italian region . PATIENTS All patients with major trauma ( Injury Severity Score , > or=16 ) and severe head injury ( Abbreviated Injury Scale score for the head , > or=4 ) rescued alive from March 1 , 1998 , to February 28 , 1999 , who received either form of care . Patients with self-inflicted injuries were excluded . The 184 patients who met the entry criteria were divided equally between care groups . INTERVENTIONS None . MAIN OUTCOME MEASURES Mortality at 30 days and Glasgow Outcome Scale score of survivors . RESULTS After verifying the comparability of the cohorts , no survival or disability benefit could be demonstrated ( 95 % confidence interval [ CI ] of the odds ratio for mortality [ helicopter/ambulance ] [ 95 % CI 1 ] , 0.72 to 2.67 ; 95 % CI of the difference in Glasgow Outcome Scale score medians between helicopter and ambulance groups [ 95 % CI 2 ] , 0.0 to 0.0 ) . Similar results were derived from analyses restricted to the subgroups identified by low ( < or=90 mm Hg ) roadside systolic blood pressure ( 95 % CI 1 , 0.58 to 7.17 ; 95 % CI 2 , -1 to 2 ) and by need for urgent neurosurgical intervention ( 95 % CI 1 , 0.16 to 2.60 ; 95 % CI 2 , 0 to 2 ) . Exclusion from the ambulance group of victims rescued in urban areas did not change the results ( 95 % CI 1 , 0.80 to 3.24 ; 95 % CI 2 , 0.0 to 0.0 ) . Stratification by age , Injury Severity Score , and Glasgow Coma Scale score demonstrated a small survival benefit ( 95 % CI 1 , 1.12 to 2.12 ) in the ambulance subgroup with Glasgow Coma Scale score from 10 to 12 . Multiple logistic regression analysis confirmed that the group did not affect mortality . CONCLUSION This study was conceived to emphasize the supposed advantages of the combined helicopter , physician , and advanced life-support rescue . No increased benefit compared with the simpler rescue group could be demonstrated BACKGROUND Significant controversy surrounds the prehospital management of trauma patients . METHODS A question naire describing clinical scenarios was mailed to a r and om sample of 345 trauma practitioners . RESULTS The 182 trauma practitioners ( 52.8 % ) who returned the surveys were predominantly general or trauma surgeons ( 83.5 % ) in academic or university practice ( 68.1 % ) . For a patient with a severe traumatic brain injury , 84.5 % of trauma practitioners recommended that emergency medical services personnel attempt intubation at least once when transport time was 20 to 40 minutes . For a patient with a gunshot wound to the epigastrium in decompensated shock , the majority of trauma practitioners believed that a relatively hypotensive state should be maintained , regardless of transport time . Trauma practitioners ( 52.2 % ) have recommended the use of the pneumatic antishock garment for transports of 20 to 40 minutes for patients with an unstable pelvic fracture and decompensated shock . CONCLUSIONS Most trauma practitioners believe that emergency medical services providers should attempt intubation for a patient with a severe traumatic brain injury , should treat decompensated shock in a patient with penetrating torso trauma but maintain the patient in a relatively hypotensive state , and should apply and inflate the pneumatic antishock garment for a suspected pelvic fracture accompanied by decompensated shock if the patient is 20 to 40 minutes from a trauma center . The recommendations of trauma practitioners regarding appropriate prehospital care are significantly influenced by the time required for transport to the trauma center INTRODUCTION Fasciculations during rapid-sequence intubation may lead to increased intracranial pressure and emesis with aspiration . St and ard rapid-sequence intubation requires a nondepolarizing blocking agent before succinylcholine administration . HYPOTHESIS Prevention of fasciculations during rapid-sequence intubation of head trauma patients can be accomplished as safely and effectively with minidose succinylcholine as with a defasciculating dose of pancuronium . DESIGN A prospect i ve , r and omized , double-blind study . SETTING An inner-city county trauma center with 70,000 patient visits per year . PARTICIPANTS Sequential adult head trauma patients requiring rapid-sequence intubation who had no contraindications to succinylcholine or pancuronium . INTERVENTIONS Each head trauma patient requiring rapid-sequence intubation who met the inclusion criteria received st and ard rapid-sequence intubation maneuvers and lidocaine ( 1 mg/kg ) IV . Patients were r and omized to receive either minidose succinylcholine ( 0.1 mg/kg ) or pancuronium ( 0.03 mg/kg ) IV one minute prior to the full paralytic dose of succinylcholine ( 1.5 mg/kg ) IV . Fasciculations were recorded using a grade d visual scale . RESULTS Of 46 patients , eight of 19 ( 42 % ) in the pancuronium group and six of 27 ( 22 % ) in the succinylcholine group experienced fasciculations . No statistically significant difference in fasciculations was detected between the two groups using chi 2 analysis . Complete relaxation of the cords was present in all but two patients , one in each group . No patient in either group experienced emesis or significant dysrhythmias . CONCLUSION Pretreatment with minidose succinylcholine causes no greater incidence of fasciculations than pancuronium in rapid-sequence intubation of head trauma patients in an ED setting . Thus succinylcholine may be used as the sole paralytic agent in rapid-sequence intubation of head trauma patients Prehospital hypoxia and hypotension increase morbidity and mortality in head-injured patients . Etomi date is a sedative agent with increasing use for emergent rapid-sequence intubation ( RSI ) because of its favorable hemodynamic profile . This prospect i ve , observational study documents the authors ' preliminary experience with etomi date as part of an aeromedical RSI protocol . Major trauma victims received etomi date 0.1 to 0.3 mg/kg intravenously ( IV ) before administration of a neuromuscular-blocking agent . After confirmation of endotracheal tube position , 1 to 2 mg midazolam IV was administered . The main outcome measure was systolic blood pressure ( SBP ) before and after the RSI procedure and the incidence of hypotension after RSI ; individual patient plots of SBP versus time were also included for graphic analysis . An improvement in SBP after RSI with etomi date was observed ( 123 mm Hg to 136 mm Hg , p = 0.011 ) with a 9 % incidence of hypotension , defined as a decrease in SBP to 90 mm Hg or less . Graphic analysis of individual SBP-time plots reveals hemodynamic stability , especially in patients with lower initial SBP values . These data suggest that the use of etomi date as part of a prehospital RSI protocol is associated with hemodynamic stability and a low incidence of hypotension BACKGROUND An increase in mortality has been documented in association with paramedic rapid sequence intubation ( RSI ) of severely head-injured patients . This analysis explores the impact of hypoxia and hyperventilation on outcome . METHODS Adult severely head-injured patients ( Glasgow Coma Scale score of 3 - 8 ) unable to be intubated without neuromuscular blockade underwent paramedic RSI using midazolam and succinylcholine ; rocuronium was administered after confirmation of tube position . St and ard ventilation parameters were used for most patients ; however , one agency instituted use of digital end-tidal carbon dioxide ( ETCO2 ) and oxygen saturation ( Spo2 ) monitoring during the trial . Each patient undergoing digital ETCO2/Spo2 monitoring was matched to three historical nonintubated controls on the basis of age , gender , mechanism , and Abbreviated Injury Scale scores for each of six body regions . Logistic regression was used to explore the impact of oxygen desaturation during laryngoscopy and postintubation hypocapnia and hypoxia on outcome . The relationship between hypocapnia and ventilatory rate was explored using linear regression and univariate analysis . In addition , trial patients and controls were compared with regard to mortality and the incidence of " good outcomes " using an odds ratio analysis . RESULTS Of the 426 trial patients , a total of 59 had complete ETCO2/Spo2 monitoring data ; these were matched to 177 controls . Logistic regression revealed an association between the lowest ETCO2 value and final ETCO2 value and mortality . Matched-controls analysis confirmed an association between hypocapnia and mortality . A statistically significant association between ventilatory rate and ETCO2 value was observed ( r = -0.13 , p < 0.0001 ) ; the median ventilatory rate associated with the lowest recorded ETCO2 value was significantly higher than for all other ETCO2 values ( 27 mm Hg vs. 19 mm Hg , p < 0.0001 ) . In addition , profound desaturations during RSI and hypoxia after intubation were associated with higher mortality than matched controls . Overall mortality was 41 % for trial patients versus 22 % for matched controls ( odds ratio , 2.51 ; 95 % confidence interval , 1.33 - 4.72 ; p = 0.004 ) . CONCLUSIONS Hyperventilation and severe hypoxia during paramedic RSI are associated with an increase in mortality |
13,876 | 27,848,034 | At this point , no final conclusion can be made regarding the efficacy of VNS to improve symptoms in psychiatric disorders other than in affective disorders | Invasive and non-invasive vagus nerve stimulation ( VNS ) is a promising add-on treatment for treatment-refractory depression , but is also increasingly evaluated for its application in other psychiatric disorders , such as dementia , schizophrenia , somatoform disorder , and others .
We performed a systematic review aim ing to give a detailed overview of the available evidence of the efficacy of VNS for the treatment of psychiatric disorders . | Despite many pharmacological and psychosocial treatment options , schizophrenia remains a debilitating disorder . Thus , new treatment strategies rooted in the pathophysiology of the disorder are needed . Recently , vagus nerve stimulation ( VNS ) has been proposed as a potential treatment option for various neuropsychiatric disorders including schizophrenia . The objective of this study was to investigate for the first time the feasibility , safety and efficacy of transcutaneous VNS in stable schizophrenia . A bicentric r and omized , sham-controlled , double-blind trial was conducted from 2010 to 2012 . Twenty schizophrenia patients were r and omly assigned to one of two treatment groups . The first group ( active tVNS ) received daily active stimulation of the left auricle for 26 weeks . The second group ( sham tVNS ) received daily sham stimulation for 12 weeks followed by 14 weeks of active stimulation . Primary outcome was defined as change in the Positive and Negative Symptom Scale total score between baseline and week 12 . Various other secondary measures were assessed to investigate safety and efficacy . The intervention was well tolerated with no relevant adverse effects . We could not observe a statistically significant difference in the improvement of schizophrenia psychopathology during the observation period . Neither psychopathological and neurocognitive measures nor safety measures showed significant differences between study groups . Application of tVNS was well tolerated , but did not improve schizophrenia symptoms in our 26-week trial . While unsatisfactory compliance questions the feasibility of patient-controlled neurostimulation in schizophrenia , the overall pattern of symptom change might warrant further investigations in this population BACKGROUND The need for effective , long-term treatment for recurrent or chronic , treatment-resistant depression is well established . METHODS This naturalistic follow-up describes out patients with nonpsychotic major depressive ( n = 185 ) or bipolar ( I or II ) disorder , depressed phase ( n = 20 ) who initially received 10 weeks of active ( n = 110 ) or sham vagus nerve stimulation ( VNS ) ( n = 95 ) . The initial active group received another 9 months , while the initial sham group received 12 months of VNS . Participants received antidepressant treatments and VNS , both of which could be adjusted . RESULTS The primary analysis ( repeated measures linear regression ) revealed a significant reduction in 24-item Hamilton Rating Scale for Depression ( HRSD(24 ) ) scores ( average improvement , .45 points [ SE = .05 ] per month ( p < .001 ) . At exit , HRSD(24 ) response rate was 27.2 % ( 55/202 ) ; remission rate ( HRSD(24 ) < or = 9 ) was 15.8 % ( 32/202 ) . Montgomery Asberg Depression Rating Scale ( 28.2 % [ 57/202 ] ) and Clinical Global Impression-Improvement ( 34.0 % [ 68/200 ] ) showed similar response rates . Voice alteration , dyspnea , and neck pain were the most frequently reported adverse events . CONCLUSIONS These 1-year open trial data found VNS to be well tolerated , suggesting a potential long-term , growing benefit in treatment-resistant depression , albeit in the context of changes in depression treatments . Comparative long-term data are needed to determine whether these benefits can be attributed to VNS OBJECTIVE To describe the outcomes of a consecutive series of depressed patients treated with vagus nerve stimulation ( VNS ) following US Food and Drug Administration ( FDA ) approval of this intervention . METHOD We implanted a VNS device in 15 consecutive out patients with treatment-resistant major depressive episodes , including 10 with major depressive disorder and 5 with bipolar disorder ( DSM-IV criteria ) , between November 2005 and August 2006 . Existing antidepressant treatment remained fixed as far as clinical ly possible . The primary outcome was change from baseline in the Beck Depression Inventory ( BDI ) score . Outcomes were assessed at 6 and 12 months postimplant and compared to those of the VNS pivotal efficacy trial that led to FDA approval of VNS . RESULTS The BDI score decreased significantly compared to baseline at 6 months ( P < .05 ) and 12 months ( P < .01 ) , from a mean of 37.8 ( SD = 7.8 ) before VNS activation to a mean of 24.6 ( SD = 11.4 ) at 12 months . By 1 year , 28.6 % ( n = 4 ) of the sample responded to VNS and 7.1 % ( n = 1 ) remitted according to the BDI . Secondary outcomes on the Hamilton Depression Rating Scale 24-Item showed similar improvement at 1 year , with a 43 % response rate ( n = 6 ) and 14.3 % remission rate ( n = 2 ) . No obvious predictors of response were detected . Side effects of VNS included hoarseness ( 73 % ) , dyspnea ( 47 % ) , nausea ( 40 % ) , pain ( 33 % ) , and anxiety ( 20 % ) ; no patient terminated treatment due to intolerable side effects . CONCLUSIONS We found that a substantial minority of patients with extremely difficult-to-treat depressive disorders benefited from VNS in an ambulatory clinical practice , with outcomes comparable to those observed in previous VNS efficacy studies and with a similar side effect profile BACKGROUND Major depressive disorder is a prevalent , disabling , and often chronic or recurrent psychiatric condition . About 35 % of patients fail to respond to conventional treatment approaches and are considered to have treatment-resistant depression ( TRD ) . OBJECTIVE We compared the safety and effectiveness of different stimulation levels of adjunctive vagus nerve stimulation ( VNS ) therapy for the treatment of TRD . METHODS In a multicenter , double blind study , 331 patients with TRD were r and omized to one of three dose groups : LOW ( 0.25 mA current , 130 μs pulse width ) , MEDIUM ( 0.5 - 1.0 mA , 250 μs ) , or HIGH ( 1.25 - 1.5 mA , 250 μs ) . A highly treatment-resistant population ( > 97 % had failed to respond to ≥6 previous treatments ) was enrolled . Response and adverse effects were assessed for 22 weeks ( end of acute phase ) , after which output current could be increased , if clinical ly warranted . Assessment s then continued until Week 50 ( end of long-term phase ) . RESULTS VNS therapy was well tolerated . During the acute phase , all groups showed statistically significant improvement on the primary efficacy endpoint ( change in Inventory of Depressive Symptomatology-Clinician Administered Version [ IDS-C ] ) , but not for any between-treatment group comparisons . In the long-term phase , mean change in IDS-C scores showed continued improvement . Post-hoc analyses demonstrated a statistically significant correlation between total charge delivered per day and decreasing depressive symptoms ; and analysis of acute phase responders demonstrated significantly greater durability of response at MEDIUM and HIGH doses than at the LOW dose . CONCLUSIONS TRD patients who received adjunctive VNS showed significant improvement at study endpoint compared with baseline , and the effect was durable over 1 year . Higher electrical dose parameters were associated with response durability BACKGROUND Chronic vagus nerve stimulation ( VNS ) is effective in the management of treatment-resistant epilepsy . Open-trial evidence suggests that VNS has clinical ly significant antidepressant effects in some individuals who experience treatment-resistant major depressive episodes . However , limited information regarding the effects of VNS on neurocognitive performance exists . OBJECTIVE The primary aim of this study was to determine whether VNS leads to neurocognitive deterioration . METHOD A neuropsychological battery was administered to 27 patients with treatment-resistant depression before and after 10 weeks of VNS . Thirteen neurocognitive tests sample d the domains of motor speed , psychomotor function , language , attention , memory , and executive function . RESULTS No evidence of deterioration in any neurocognitive measure was detected . Relative to baseline , improvement in motor speed ( finger tapping ) , psychomotor function ( digit-symbol test ) , language ( verbal fluency ) , and executive functions ( logical reasoning , working memory , response inhibition , or impulsiveness ) was found . For some measures , improved neurocognitive performance correlated with the extent of reduction in depressive symptoms , but VNS output current was not related to changes in cognitive performance . CONCLUSIONS Vagus nerve stimulation in treatment-resistant depression may result in enhanced neurocognitive function , primarily among patients who show clinical improvement . Controlled investigation is needed to rule out the contribution of practice effects This open pilot study of vagus nerve stimulation ( VNS ™ ) in 60 patients with treatment-resistant major depressive episodes ( MDEs ) aim ed to : 1 ) define the response rate ; 2 ) determine the profile of side effects ; and , most importantly ; 3 ) establish predictors of clinical outcome . Participants were out patients with nonatypical , nonpsychotic , major depressive or bipolar disorder who had not responded to at least two medication trials from different antidepressant classes in the current MDE . While on stable medication regimens , the patients completed a baseline period followed by device implantation . A 2-week , single blind , recovery period ( no stimulation ) was followed by 10 weeks of VNS . Of 59 completers ( one patient improved during the recovery period ) , the response rate was 30.5 % for the primary HRSD28 measure , 34.0 % for the Montgomery-Äsberg Depression Rating Scale ( MADRAS ) , and 37.3 % for the Clinical Global Impression-Improvement Score ( CGI-I of 1 or 2 ) . The most common side effect was voice alteration or hoarseness , 55.0 % ( 33/60 ) , which was generally mild and related to output current intensity . History of treatment resistance was predictive of VNS outcome . Patients who had never received ECT ( lifetime ) were 3.9 times more likely to respond . Of the 13 patients who had not responded to more than seven adequate antidepressant trials in the current MDE , none responded , compared to 39.1 % of the remaining 46 patients ( p = .0057 ) . Thus , VNS appears to be most effective in patients with low to moderate , but not extreme , antidepressant resistance . Evidence concerning VNS ' long-term therapeutic benefits and tolerability will be critical in determining its role in treatment-resistant depression AIM The purpose of this study was to evaluate the efficacy of vagus nerve stimulation ( VNS ) as a therapeutic option for treatment-resistant depression ( TRD ) , with follow-up periods of 1 , 3 and 5 years after VNS surgery . METHODS We examined 27 consecutive patients with unipolar TRD . Depressive symptoms were evaluated both at baseline and at follow-up after the surgery by means of the 21-item Hamilton Rating Scale for Depression ( HAM-D 21 ) . RESULTS The mean HAM-D preoperative score was 25.6 . Twenty-two patients were evaluated after 1 year of treatment , and the mean improvement of the HAM-D score was of 10.3 . Five patients ( 20 % ) went into complete remission ( HAM-D < 7 ) after 1 year , six patients ( 22.3 % ) were considered responders ( 50 % reduction of HAM-D scoring ) and eight patients had score reduction of less then 20 % . Nineteen patients were evaluated after 24–36 months : the average improvement on the HAM-D score was of 12.1 points ( 47.2 % ) . One patient went into complete remission and eight patients ( 42.1 % ) were responders . Up to the present date , seven patients have undergone re-evaluation at 48–60 months from surgery showing an average score reduction of 14.2 . Two more patients obtained complete remission , while four of them did not have any improvement since their last follow-up control visit . CONCLUSION VNS antidepressant was successful in 20 % of TRD patients , although some patients required several months to obtain clinical improvement or remission of symptomatology . Nonetheless this procedure can be considered as a useful option in treating TRD BACKGROUND Vagus nerve stimulation ( VNS ) alters both concentrations of neurotransmitters or their metabolites and functional activity of central nervous system regions dysregulated in mood disorders . An open trial has suggested efficacy . METHODS This 10-week , acute , r and omized , controlled , masked trial compared adjunctive VNS with sham treatment in 235 out patients with nonpsychotic major depressive disorder ( n = 210 ) or nonpsychotic , depressed phase , bipolar disorder ( n = 25 ) . In the current episode , participants had not responded adequately to between two and six research -qualified medication trials . A two-week , single-blind recovery period ( no stimulation ) and then 10 weeks of masked active or sham VNS followed implantation . Medications were kept stable . Primary efficacy outcome among 222 evaluable participants was based on response rates ( > /=50 % reduction from baseline on the 24-item Hamilton Rating Scale for Depression [ HRSD(24 ) ] ) . RESULTS At 10-weeks , HRSD(24 ) response rates were 15.2 % for the active ( n = 112 ) and 10.0 % for the sham ( n = 110 ) groups ( p = .251 , last observation carried forward [ LOCF ] ) . Response rates with a secondary outcome , the Inventory of Depressive Symptomatology - Self-Report ( IDS-SR(30 ) ) , were 17.0 % ( active ) and 7.3 % ( sham ) ( p = .032 , LOCF ) . VNS was well tolerated ; 1 % ( 3/235 ) left the study because of adverse events . CONCLUSIONS This study did not yield definitive evidence of short-term efficacy for adjunctive VNS in treatment-resistant depression To eluci date , in a pilot‐ study , whether noninvasive transcutaneous vagus nerve stimulation ( t‐VNS ) is a safe and tolerable alternative treatment option in pharmacoresistant epilepsy . t‐VNS was applied to 10 patients with pharmacoresistant epilepsies . Stimulation via the auricular branch of the vagus nerve of the left tragus was delivered three times per day for 9 months . Subjective documentation of stimulation effects was obtained from patients ’ seizure diaries . For a more reliable assessment of seizure frequency , we carried out prolonged outpatient video – electroencephalography ( EEG ) monitoring . In addition , computerized testing of cognitive , affective , and emotional functions was performed . Three patients aborted the study . Of the remaining seven patients , an overall reduction of seizure frequency was observed in five patients after 9 months of t‐VNS . The noninvasive t‐VNS stimulation is a safe and well‐tolerated method for relatively long periods , and might be an alternative treatment option for patients with epilepsy BACKGROUND Depression presents a significant burden to both patients and society . One treatment that has emerged is vagus nerve stimulation ( VNS ) , an FDA -approved physical treatment for depressive disorders . However , the application of this intervention has been limited by the involvement of surgery and potential side effects . The aim of this study is to explore the effectiveness of stimulating the superficial branches of the vagus nerve as a solo treatment for MDD . METHODS This is a nonr and omized , controlled study . The first cohort of patients ( n=91 ) only received transcutaneous auricular VNS ( taVNS ) for 12 weeks . In the second cohort ( n=69 ) , patients first received 4 weeks of sham taVNS followed by 8 weeks of taVNS . All treatments were self-administered by the patients at home after they received training from the hospitals . The primary outcome measurement was the 24-item Hamilton Depression Rating Scale measured at weeks 0 , 4 , 8 , and 12 . Data analysis included a timelag analysis comparing ( 1 ) real and sham taVNS groups at week 4 ; ( 2 ) the real taVNS group at week 4 vs the sham taVNS group at week 8 ( fourth week of real taVNS following 4 weeks of sham ) ; and ( 3 ) the real taVNS group at week 8 vs the sham taVNS group at week 12 ( eighth week of real taVNS following sham ) . RESULTS After four weeks of treatment , MDD patients in the taVNS group showed greater improvement than patients in the sham taVNS group as indicated by Hamilton score changes as well as response and remission rates at week four . In addition , we also found that the clinical improvements continued until week 12 during taVNS . LIMITATIONS Patients were not r and omized in this study . CONCLUSIONS Our results suggest that taVNS is a promising , safe , and cost-effective therapeutic method for mild and moderate MDD OBJECTIVE We performed an open-label Phase I/II trial to evaluate the safety and tolerability of vagus nerve stimulation ( VNS ) in patients with treatment-resistant fibromyalgia ( FM ) as well as to determine preliminary measures of efficacy in these patients . METHODS Of 14 patients implanted with the VNS stimulator , 12 patients completed the initial 3-month study of VNS ; 11 patients returned for follow-up visits 5 , 8 , and 11 months after start of stimulation . Therapeutic efficacy was assessed with a composite measure requiring improvement in pain , overall wellness , and physical function . Loss of both pain and tenderness criteria for the diagnosis of FM was added as a secondary outcome measure because of results found at the end of 3 months of stimulation . RESULTS Side effects were similar to those reported in patients treated with VNS for epilepsy or depression and , in addition , dry mouth and fatigue were reported . Two patients did not tolerate stimulation . At 3 months , five patients had attained efficacy criteria ; of these , two patients no longer met widespread pain or tenderness criteria for the diagnosis of FM . The therapeutic effect seemed to increase over time in that additional participants attained both criteria at 11 months . CONCLUSIONS Side effects and tolerability were similar to those found in disorders currently treated with VNS . Preliminary outcome measures suggested that VNS may be a useful adjunct treatment for FM patients resistant to conventional therapeutic management , but further research is required to better underst and its actual role in the treatment of FM OBJECTIVE Vagus nerve stimulation ( VNS ) appears to be an effective treatment option for patients with treatment-resistant unipolar and bipolar depression . The aim of the present study was to investigate the efficacy of VNS in a group of patients with treatment-resistant rapid-cycling bipolar disorder ( RCBD ) who were excluded from previous trials . METHOD Nine out patients with a DSM-IV-TR diagnosis of treatment-resistant RCBD were treated for 40 weeks with open-label VNS . The first patient was enrolled in June 2001 , and the last patient completed the study in July 2005 . Patients recorded their depression and mania mood symptoms on a daily basis throughout the study using the National Institute of Mental Health prospect i ve life charting methodology and daily mood ratings . Patients were assessed every 2 weeks during the 2-month baseline period before device activation , every 2 weeks for the remaining 40 weeks of the study , and at the end of the study with the 24-item Hamilton Rating Scale for Depression ( HAM-D-24 ) , the 10-item Montgomery-Asberg Depression Rating Scale ( MADRS ) , the Young Mania Rating Scale ( YMRS ) , the Clinical Global Impressions ( CGI ) scale , the Global Assessment of Functioning ( GAF ) scale , and the 30-item Inventory of Depressive Symptomatology Self-Report ( IDS-SR-30 ) . Any adverse events or device complications were also recorded at each visit . The prospect i ve life charts were analyzed by calculating the area under the curve . Statistical analysis was performed with a mixed-model repeated- measures regression analysis for repeated measures of the various rating scales . Significant p values were < or = .05 . RESULTS Over the 12-month study period , VNS was associated with a 38.1 % mean improvement in overall illness as compared to baseline ( p = .012 ) , as well as significant reductions in symptoms as measured by the HAM-D-24 ( p = .043 ) , MADRS ( p = .003 ) , CGI ( p = .013 ) , and GAF ( p < .001 ) rating scales . Common adverse events were voice alteration during stimulation and hoarseness . CONCLUSION These data suggest that VNS may be an efficacious and well-tolerated treatment option for patients with treatment-resistant RCBD . Currently , no comparison is available in the literature . Larger r and omized trials are needed to verify these findings BACKGROUND To evaluate clinical aspects and cost effectiveness of the treatment with vagus nerve stimulation ( VNS ) , a group of 9 VNS-implanted patients and 9 age- and sex-matched patients suffering from treatment-resistant depression were included in a prospect i ve study . METHODS The psychopathological ratings over 12 months as well as socio-economic data on the duration of hospitalisation , frequency of outpatient treatment , and subsequent drug treatment were compared with the pre-implantation period . RESULTS Compared with baseline values in the HAMD scale ( mean 23.7 ; SD 2.4 ) , there was a significant ( t=14.5 ; df=8 ; p<0.001 ) improvement in symptoms after 12 months ' stimulation ( mean 10.2 ; SD 2.4 ) . The duration of hospitalisation dropped on average by 20 days in the first post-implantation year , the treatment frequency from 33 to 14 visits , and drug treatment from 4 to an average of 3 psychotropic drugs . CONCLUSION In addition to an improvement in clinical symptoms , the VNS method might enable an amortisation of costs BACKGROUND Vagus Nerve Stimulation ( VNS ) delivered by the NeuroCybernetic Prosthesis ( NCP ) System was examined for its potential antidepressant effects . METHODS Adult out patients ( n = 30 ) with nonpsychotic , treatment-resistant major depressive ( n = 21 ) or bipolar I ( n = 4 ) or II ( n = 5 ; depressed phase ) disorders who had failed at least two robust medication trials in the current major depressive episode ( MDE ) while on stable medication regimens completed a baseline period followed by NCP System implantation . A 2-week , single-blind recovery period ( no stimulation ) was followed by 10 weeks of VNS . RESULTS In the current MDE ( median length = 4.7 years ) , patients had not adequately responded to two ( n = 9 ) , three ( n = 2 ) , four ( n = 6 ) , or five or more ( n = 13 ) robust antidepressant medication trials or electroconvulsive therapy ( n = 17 ) . Baseline 28-item Hamilton Depression Rating Scale ( HDRS(28 ) ) scores averaged 38.0 . Response rates ( > or = 50 % reduction in baseline scores ) were 40 % for both the HDRS(28 ) and the Clinical Global Impressions-Improvement index ( score of 1 or 2 ) and 50 % for the Montgomery-Asberg Depression Rating Scale . Symptomatic responses ( accompanied by substantial functional improvement ) have been largely sustained during long-term follow-up to date . CONCLUSIONS These open trial results suggest that VNS has antidepressant effects in treatment-resistant depressions Invasive vagus nerve stimulation has been demonstrated to be an effective treatment in major depressive episodes . Recently , a novel non-invasive method of stimulating the vagus nerve on the outer canal of the ear has been proposed . In healthy subjects , a prominent fMRI BOLD signal deactivation in the limbic system was found . The present pilot study investigates the effects of this novel technique of auricular transcutaneous electric nerve stimulation in depressed patients for the first time . A total of 37 patients suffering from major depression were included in two r and omized sham controlled add-on studies . Patients were stimulated five times a week on a daily basis for the duration of 2 weeks . On days 0 and 14 , the Hamilton Depression Rating Scale ( HAMD ) and the Beck Depression Inventory ( BDI ) were assessed . In contrast to sham-treated patients , electrically stimulated persons showed a significantly better outcome in the BDI . Mean decrease in the active treatment group was 12.6 ( SD 6.0 ) points compared to 4.4 ( SD 9.9 ) points in the sham group . HAMD score did not change significantly in the two groups . An antidepressant effect of a new transcutaneous auricular nerve stimulation technique has been shown for the first time in this controlled pilot study . Regarding the limitations of psychometric testing , the risk of unblinding for technical reasons , and the small sample size , further studies are necessary to confirm the present results and verify the practicability of tVNS in clinical fields BACKGROUND It has recently been shown that electrical stimulation of sensory afferents within the outer auditory canal may facilitate a transcutaneous form of central nervous system stimulation . Functional magnetic resonance imaging ( fMRI ) blood oxygenation level dependent ( BOLD ) effects in limbic and temporal structures have been detected in two independent studies . In the present study , we investigated BOLD fMRI effects in response to transcutaneous electrical stimulation of two different zones in the left outer auditory canal . It is hypothesized that different central nervous system ( CNS ) activation patterns might help to localize and specifically stimulate auricular cutaneous vagal afferents . METHODOLOGY 16 healthy subjects aged between 20 and 37 years were divided into two groups . 8 subjects were stimulated in the anterior wall , the other 8 persons received transcutaneous vagus nervous stimulation ( tVNS ) at the posterior side of their left outer auditory canal . For sham control , both groups were also stimulated in an alternating manner on their corresponding ear lobe , which is generally known to be free of cutaneous vagal innervation . Functional MR data from the cortex and brain stem level were collected and a group analysis was performed . RESULTS In most cortical areas , BOLD changes were in the opposite direction when comparing anterior vs. posterior stimulation of the left auditory canal . The only exception was in the insular cortex , where both stimulation types evoked positive BOLD changes . Prominent decreases of the BOLD signals were detected in the parahippocampal gyrus , posterior cingulate cortex and right thalamus ( pulvinar ) following anterior stimulation . In subcortical areas at brain stem level , a stronger BOLD decrease as compared with sham stimulation was found in the locus coeruleus and the solitary tract only during stimulation of the anterior part of the auditory canal . CONCLUSIONS The results of the study are in line with previous fMRI studies showing robust BOLD signal decreases in limbic structures and the brain stem during electrical stimulation of the left anterior auditory canal . BOLD signal decreases in the area of the nuclei of the vagus nerve may indicate an effective stimulation of vagal afferences . In contrast , stimulation at the posterior wall seems to lead to unspecific changes of the BOLD signal within the solitary tract , which is a key relay station of vagal neurotransmission . The results of the study show promise for a specific novel method of cranial nerve stimulation and provide a basis for further developments and applications of non-invasive transcutaneous vagus stimulation in psychiatric patients BACKGROUND Previous reports have described the effects of vagus nerve stimulation plus treatment as usual ( VNS+TAU ) during open trials of patients with treatment-resistant depression ( TRD ) . To better underst and these effects on long-term outcome , we compared 12-month VNS+TAU outcomes with those of a comparable TRD group . METHODS Admission criteria were similar for those receiving VNS+TAU ( n = 205 ) or only TAU ( n = 124 ) . In the primary analysis , repeated- measures linear regression was used to compare the VNS+TAU group ( monthly data ) with the TAU group ( quarterly data ) according to scores of the 30-item Inventory of Depressive Symptomatology-Self-Report ( IDS-SR(30 ) ) . RESULTS The two groups had similar baseline demographic data , psychiatric and treatment histories , and degrees of treatment resistance , except that more TAU participants had at least 10 prior major depressive episodes , and the VNS+TAU group had more electroconvulsive therapy before study entry . Vagus nerve stimulation plus treatment as usual was associated with greater improvement per month in IDS-SR(30 ) than TAU across 12 months ( p < .001 ) . Response rates according to the 24-item Hamilton Rating Scale for Depression ( last observation carried forward ) at 12 months were 27 % for VNS+TAU and 13 % for TAU ( p < .011 ) . Both groups received similar TAU ( drugs and electroconvulsive therapy ) during follow-up . CONCLUSIONS This comparison of two similar but nonr and omized TRD groups showed that VNS+TAU was associated with a greater antidepressant benefit over 12 months BACKGROUND Cognitive-enhancing effects of vagus nerve stimulation ( VNS ) have been reported during 6 months of treatment in a pilot study of patients with Alzheimer 's disease ( AD ) . Data through 1 year of VNS ( collected from June 2000 to September 2003 ) are now reported . METHOD All patients ( N = 17 ) met the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer 's Disease and Related Disorders Association ( NINCDS-ADRDA ) criteria for probable AD . Responder rates for the Alzheimer 's Disease Assessment Scale-cognitive subscale ( ADAS-cog ) and Mini-Mental State Examination ( MMSE ) were measured as improvement or absence of decline from baseline . Global change , depressive symptoms , and quality of life were also assessed . Cerebrospinal fluid ( CSF ) levels for total tau , tau phosphorylated at Thr181 ( phosphotau ) , and Abeta42 were measured by st and ardized enzyme-linked immunosorbent assay ( ELISA ) . RESULTS VNS was well tolerated . After 1 year , 7 ( 41.2 % ) of 17 patients and 12 ( 70.6 % ) of 17 patients improved or did not decline from baseline on the ADAS-cog and MMSE , respectively . Twelve of 17 patients were rated as having no change or some improvement from baseline on the Clinician Interview-Based Impression of Change ( CIBIC+ ) . No significant decline in mood , behavior , or quality of life occurred during 1 year of treatment . The median change in CSF tau at 1 year was a reduction of 4.8 % ( p = .057 ) , with a 5.0 % increase in phosphotau ( p = .040 ; N = 14 ) . CONCLUSION The results of this study support long-term tolerability of VNS among patients with AD and warrant further investigation BACKGROUND Vagus nerve stimulation ( VNS ) had antidepressant effects in an initial open , acute phase pilot study of 59 participants in a treatment-resistant major depressive episode ( MDE ) . We examined the effects of adjunctive VNS over 24 months in this cohort . METHOD Adult out patients ( N = 59 ) with chronic or recurrent major depressive disorder or bipolar ( I or II ) disorder and experiencing a treatment-resistant , nonpsychotic MDE ( DSM-IV criteria ) received 2 years of VNS . Changes in psychotropic medications and VNS stimulus parameters were allowed only after the first 3 months . Response was defined as > or = 50 % reduction from the baseline 28-item Hamilton Rating Scale for Depression ( HAM-D-28 ) total score , and remission was defined as a HAM-D-28 score < or = 10 . RESULTS Based on last observation carried forward analyses , HAM-D-28 response rates were 31 % ( 18/59 ) after 3 months , 44 % ( 26/59 ) after 1 year , and 42 % ( 25/59 ) after 2 years of adjunctive VNS . Remission rates were 15 % ( 9/59 ) at 3 months , 27 % ( 16/59 ) at 1 year , and 22 % ( 13/59 ) at 2 years . By 2 years , 2 deaths ( unrelated to VNS ) had occurred , 4 participants had withdrawn from the study , and 81 % ( 48/59 ) were still receiving VNS . Longer-term VNS was generally well tolerated . CONCLUSION These results suggest that patients with chronic or recurrent , treatment-resistant depression may show long-term benefit when treated with VNS The present paper evaluates the efficacy of low frequency , high intensity auricular transcutaneous electrical nerve stimulation ( TENS ) for the relief of phantom limb pain . Auricular TENS was compared with a no-stimulation placebo condition using a controlled crossover design in a group of amputees with ( 1 ) phantom limb pain ( Group PLP ) , ( 2 ) nonpainful phantom limb sensations ( Group PLS ) , and ( 3 ) no phantom limb at all ( Group No PL ) . Small , but significant , reductions in the intensity of nonpainful phantom limb sensations were found for Group PLS during the TENS but not the placebo condition . In addition , 10 min after receiving auricular TENS , Group PLP demonstrated a modest , yet statistically significant decrease in pain as measured by the McGill Pain Question naire . Ratings of mood , sleepiness , and anxiety remained virtually unchanged across test occasions and sessions , indicating that the decrease in pain was not mediated by emotional factors . Further placebo-controlled trials of auricular TENS in patients with phantom limb pain are recommended in order to evaluate the importance of electrical stimulation parameters such as pulse width and rate , and to establish the duration of pain relief The purpose of the present study was to assess the effects of vagus nerve stimulation ( VNS ) therapy on regional cerebral blood flow ( rCBF ) in depressed patients . Regional cerebral blood flow ( rCBF ) was assessed by [(99m)Tc]-HMPAO-single photon emission computed tomography ( SPECT ) before and after 10weeks of VNS in patients participating in an open , uncontrolled European multi-center study investigating efficacy and safety of VNS . Patients suffered from major depression , with a baseline score of≥20 on the 24-item Hamilton Depression Rating Scale ( HDRS ) and had been unsuccessfully treated with at least two adequately prescribed antidepressant drugs . Data of 15 patients could be analyzed using SPM 2 . After 10weeks of VNS ( 20Hz , 500μs pulse width , stimulation during 30s every 5min at the maximal comfortable level ) rCBF was increased in the left dorsolateral/ventrolateral prefrontal cortex ( Brodmann areas 46 and 47 ) and decreased in the right posterior cingulate area , the lingual gyrus and the left insula . Our findings are in line with earlier results which showed that VNS increases rCBF in the left dorsolateral prefrontal cortex . The modulation of the activity in this region could be associated with the antidepressant efficacy of VNS One of the major goals of antidepressant treatment is a sustained response and remission of depressive symptoms . Some of the previous studies of vagus nerve stimulation ( VNS ) have suggested antidepressant effects . Our naturalistic study assessed the efficacy and the safety of VNS in 74 European patients with therapy-resistant major depressive disorder . Psychometric measures were obtained after 3 , 12 , and 24 months of VNS . Mixed-model repeated- measures analysis of variance revealed a significant reduction ( P ≤ 0.05 ) at all the 3 time points in the 28-item Hamilton Rating Scale for Depression ( HRSD28 ) score , the primary outcome measure . After 2 years , 53.1 % ( 26/49 ) of the patients fulfilled the response criteria ( ≥50 % reduction in the HRSD28 scores from baseline ) and 38.9 % ( 19/49 ) fulfilled the remission criteria ( HRSD28 scores ≤ 10 ) . The proportion of patients who fulfilled the remission criteria remained constant as the duration of VNS treatment increased . Voice alteration , cough , and pain were the most frequently reported adverse effects . Two patients committed suicide during the study ; no other deaths were reported . No statistically significant differences were seen in the number of concomitant antidepressant medications . The results of this 2-year open-label trial suggest a clinical response and a comparatively benign adverse effect profile among patients with treatment-resistant depression |
13,877 | 22,843,207 | Results While the discovery of animal insulin significantly decreased mortality rates from diabetes , issues with availability and large variability between batches led to difficulty in determining proper doses and , subsequently , challenges in achieving glycemic control and avoiding hypoglycemia .
The development of synthetic insulin created a more readily available supply , but hypoglycemia still persisted .
Recombinant DNA technology solved insulin production problems and allowed for the development of better retarding agents , but pharmacokinetic/pharmacodynamic profiles still did not mimic natural insulin .
Insulin premixes offered improved glycemic control , decreased intrapatient variability versus self-mixing , and required fewer injections per day ; however , patient adherence remained a problem due to the need to inject 30–60 minutes before a meal for optimal control .
This prompted the development of rapid-acting insulin analogs that could be injected right before a meal and long-acting insulin analogs with flatter time-action profiles .
Newer insulin analogs and more convenient routes of insulin delivery have shown promising safety and efficacy results . | Introduction Although insulin products and treatment strategies have improved significantly , clinical challenges still exist .
Meeting glycemic goals while minimizing glucose variability and hypoglycemia is of utmost importance when considering existing insulin therapies and design ing investigational insulin treatments .
Many patients with diabetes have not reached glycemic goals on currently available insulins . | OBJECTIVE To study the pharmacodynamic properties of the subcutaneously injected long-acting insulin analog HOE901 ( 30 microg/ml zinc ) in comparison with those of NPH insulin and placebo . RESEARCH DESIGN AND METHODS In this single-center double-blind euglycemic glucose clamp study , 15 healthy male volunteers ( aged 27 + /- 4 years , BMI 22.2 + /- 1.8 kg/m2 ) received single subcutaneous injections of 0.4 U/kg body wt of HOE901 , NPH insulin , or placebo on 3 study days in a r and omized order . The necessary glucose infusion rates ( GIRs ) to keep blood glucose concentrations constant at 5.0 mmol/l were determined over a 30-h period after administration . RESULTS The injection of HOE901 did not induce the pronounced peak in metabolic activity observed with NPH insulin ( GIRmax 5.3 + /- 1.1 vs. 7.7 + /- 1.3 mg x kg(-1 ) x min(-1 ) ) ( P < 0.05 ) ; after an initial rise , metabolic activity was rather constant over the study period . This lack of peak was confirmed by a lower glucose consumption in the first 4 h after injection ( area under the curve from 0 to 4 h [ AUC(0 - 4 h ) ] 1.02 + /- 0.34 vs. 1.48 + /- 0.34 g/kg ) ( P < 0.001 ) with HOE901 , as compared with NPH insulin . In this single-dose study , the metabolic effect measured over a period of 30 h was lower with HOE901 than with NPH insulin ( AUC(0 - 30 h ) 7.93 + /- 1.82 vs. 9.24 + /- 1.29 g/kg ) ( P < 0.05 ) . CONCLUSIONS This study shows that the soluble long-acting insulin analog HOE901 induces a smoother metabolic effect than NPH insulin , from which a better substitution of basal insulin requirements may follow Insulin glulisine is appealing in principle , but the advantages of this drug over the other rapid-acting insulin analogs are still relatively unknown . The frequency of hypoglycemia , convenience in the timing of administration , and improvements in terms of HbA1c seem similar among the rapid-acting insulin analogs , including insulin glulisine . Only properly r and omized long-term clinical studies with insulin glulisine will reveal the true value of this novel insulin analog AIMS The IMPROVE observational study evaluated the safety profile and effectiveness of biphasic insulin aspart 30/70 ( BIAsp 30 ) in patients with type 2 diabetes in routine practice in 11 countries . METHODS Patients who initiated insulin therapy with , or switched existing insulin therapy to , BIAsp 30 in routine care were eligible for this 26-week , non-interventional observational study . Data on adverse events , hypoglycaemia and glycaemic parameters were obtained from patients ' diaries and medical notes . Question naire-based patient treatment satisfaction was also measured . We report global results and , uniquely for a diabetes observational study , country-specific data . RESULTS A total of 52,419 patients were enrolled from three pre study treatment groups : no pharmaceutical therapy ( n = 8966 , diabetes duration 2.0 years , baseline HbA1c 9.9 % ) , oral antidiabetic drugs ( OADs ) only ( n = 33,797 , diabetes duration 7.4 years , baseline HbA1c 9.2 % ) and insulin + /- OADs ( n = 9568 , diabetes duration 10.4 years , baseline HbA1c 9.3 % ) . At final visit , HbA1c , fasting and postpr and ial blood glucose were significantly reduced from baseline in all subgroups ( no pharmaceutical therapy : -3.1 % , -5.9 and -9.0 mmol/l , respectively ; OADs-only : -2.1 % , -4.1 and -6.1 mmol/l ; insulin + /- OADs : -2.0 % , -3.3 and -5.1 mmol/l ) . Major hypoglycaemia rates decreased in all subgroups ; minor hypoglycaemia increased in the insulin-naïve groups . There was no mean weight gain across subgroups . Across all countries , glycaemic parameters and major hypoglycaemia were reduced ; weight increases were seen in some countries . Treatment satisfaction increased in all subgroups and countries following BIAsp 30 therapy . CONCLUSIONS Initiating insulin with , or switching insulin therapy to , BIAsp 30 in routine care result ed in improved glycaemic control , reduced major hypoglycaemia and greater treatment satisfaction OBJECTIVE Insulin degludec ( IDeg ) is a basal insulin that forms soluble multihexamers after subcutaneous injection , result ing in an ultra-long action profile . We assessed the efficacy and safety of IDeg formulations administered once daily in combination with mealtime insulin aspart in people with type 1 diabetes . RESEARCH DESIGN AND METHODS In this 16-week , r and omized , open-label trial , participants ( mean : 45.8 years old , A1C 8.4 % , fasting plasma glucose [ FPG ] 9.9 mmol/L , BMI 26.9 kg/m2 ) received subcutaneous injections of IDeg(A ) ( 600 μmol/L ; n = 59 ) , IDeg(B ) ( 900 μmol/L ; n = 60 ) , or insulin glargine ( IGlar ; n = 59 ) , all given once daily in the evening . Insulin aspart was administered at mealtimes . RESULTS At 16 weeks , mean A1C was comparable for IDeg(A ) ( 7.8 ± 0.8 % ) , IDeg(B ) ( 8.0 ± 1.0 % ) , and IGlar ( 7.6 ± 0.8 % ) , as was FPG ( 8.3 ± 4.0 , 8.3 ± 2.8 , and 8.9 ± 3.5 mmol/L , respectively ) . Estimated mean rates of confirmed hypoglycemia were 28 % lower for IDeg(A ) compared with IGlar ( rate ratio [ RR ] : 0.72 [ 95 % CI 0.52–1.00 ] ) and 10 % lower for IDeg(B ) compared with IGlar ( RR : 0.90 [ 0.65–1.24 ] ) ; rates of nocturnal hypoglycemia were 58 % lower for IDeg(A ) ( RR : 0.42 [ 0.25–0.69 ] ) and 29 % lower for IDeg(B ) ( RR : 0.71 [ 0.44–1.16 ] ) . Mean total daily insulin dose was similar to baseline . The frequency and pattern of adverse events was similar between insulin treatments . CONCLUSIONS In this clinical exploratory phase 2 trial in people with type 1 diabetes , IDeg is safe and well tolerated and provides comparable glycemic control to IGlar at similar doses , with reduced rates of hypoglycemia Aims /hypothesisThe aim of the trial was to compare the efficacy and tolerability of two types of basal-bolus therapy , using either the soluble long-acting basal insulin analogue , insulin detemir , in combination with the rapid-acting analogue , insulin aspart , or NPH insulin in combination with mealtime regular human insulin . Methods In this 18-week , 1:1 r and omised , open-labelled , parallel trial , 595 patients with Type 1 diabetes mellitus received insulin detemir or NPH insulin in the morning and at bedtime in combination with mealtime insulin aspart or regular human insulin respectively . Results Glycaemic control with insulin detemir/insulin aspart was improved in comparison with NPH insulin/regular human insulin ( HbA1c : 7.88 % vs 8.11 % ; mean difference : −0.22 % point [ 95 % CI : −0.34 to −0.10 ] ; p<0.001 ) . Self-measured 8-point plasma glucose profiles differed between the groups ( p<0.001 ) , with lower postpr and ial plasma glucose levels in the insulin detemir/insulin aspart group . Within-person day-to-day variation in plasma glucose was lower with insulin detemir/insulin aspart than with NPH insulin/regular human insulin ( SD : 2.88 vs 3.12 mmol/l ; p<0.001 ) . Risk of overall and nocturnal hypoglycaemia ( 23.00–06.00 hours ) was , respectively , 21 % ( p=0.036 ) and 55 % ( p<0.001 ) lower in the insulin detemir/insulin aspart group than in the NPH insulin/regular human insulin group . Body weight ( adjusted for baseline and change in HbA1c ) was 1 kg lower with insulin detemir/insulin aspart than with NPH insulin/regular human insulin ( p<0.001 ) . Conclusions /interpretationBasal-bolus therapy using insulin detemir/insulin aspart offers a better balance of control and tolerability than with NPH insulin/regular human insulin . The low variability and more physiological action profiles generated with these insulin analogues result ed in improved glycaemic control with lower risk of hypoglycaemia and no concomitant body weight increase BACKGROUND The positive association between obesity and postmenopausal breast cancer has been attributed , in part , to the fact that estrogen , a risk factor for breast cancer , is synthesized in adipose tissue . Obesity is also associated with high levels of insulin , a known mitogen . However , no prospect i ve studies have directly assessed associations between circulating levels of insulin and /or insulin-like growth factor (IGF)-I , a related hormone , and the risk of breast cancer independent of estrogen level . METHODS We conducted a case-cohort study of incident breast cancer among nondiabetic women who were enrolled in the Women 's Health Initiative Observational Study ( WHI-OS ) , a prospect i ve cohort of 93,676 postmenopausal women . Fasting serum sample s obtained at study entry from 835 incident breast cancer case subjects and from a subcohort of 816 r and omly chosen WHI-OS subjects were tested for levels of insulin , glucose , total IGF-I , free IGF-I , insulin-like growth factor binding protein-3 , and estradiol . Multivariable Cox proportional hazards models were used to estimate associations between levels of the serologic factors and baseline characteristics ( including body mass index [ BMI ] ) and the risk of breast cancer . All statistical tests were two-sided . Results Insulin levels were positively associated with the risk of breast cancer ( hazard ratio [ HR ] for highest vs lowest quartile of insulin level = 1.46 , 95 % confidence interval [ CI ] = 1.00 to 2.13 , P(trend ) = .02 ) ; however , the association with insulin level varied by hormone therapy ( HT ) use ( P(interaction ) = .01 ) . In a model that controlled for multiple breast cancer risk factors including estradiol , insulin level was associated with breast cancer only among nonusers of HT ( HR for highest vs lowest quartile of insulin level = 2.40 , 95 % CI = 1.30 to 4.41 , P(trend ) < .001 ) . Obesity ( BMI > or=30 kg/m(2 ) ) was also associated with the risk of breast cancer among nonusers of HT ( HR for BMI > or=30 kg/m(2 ) vs 18.5 to < 25 kg/m(2 ) = 2.12 , 95 % CI = 1.26 to 3.58 , P(trend ) = .003 ) ; however , this association was attenuated by adjustment for insulin ( P(trend ) = .40 ) . CONCLUSION These data suggest that hyperinsulinemia is an independent risk factor for breast cancer and may have a substantial role in explaining the obesity-breast cancer relationship Insulin detemir is an analog of human insulin design ed to provide a long duration of basal insulin action . This is achieved by protracted absorption from the injection depot , which results in part from increased self-association of insulin detemir molecules and in part from reversible albumin binding . Subsequent albumin binding in the circulation is thought to buffer changes in the effects at target tissues that could otherwise arise from variability in absorption rate . In consequence , insulin detemir has shown a less variable pharmacodynamic profile than alternative basal insulins ; this manifests as more consistent temporal glucose reduction profiles in repeat-clamp studies . In clinical trials , insulin detemir has been characterized by consistent risk reductions in hypoglycemia , as well as reduced weight gain in comparison with other basal insulins . Given some recent associations that have been made in prospect i ve and epidemiologic studies between glucose variability and /or hypoglycemia and increased cardiovascular risk , and the long-known association between excess weight and cardiovascular risk , it is possible that the clinical profile of insulin detemir may carry prognostic value with regard to cardiovascular safety , although this is yet to be substantiated . There have also been some concerns raised recently over the use of insulin analogs and cancer risk , but available clinical data and the receptor interaction profile of insulin detemir suggest no excess in risk in comparison with human insulin therapy . Optimal approaches for the clinical use of insulin detemir have been emerging through an increasing clinical study base , and the analog is becoming established as a potentially valuable therapy option OBJECTIVE To investigate the pharmacodynamic profile and duration of action for five subcutaneous doses of insulin detemir ( 0.1 , 0.2 , 0.4 , 0.8 , and 1.6 units/kg ; 1 unit = 24 nmol ) and one subcutaneous dose of NPH insulin ( 0.3 IU/kg ; 1 IU = 6 nmol ) . RESEARCH DESIGN AND METHODS This single-center , r and omized , double-blind , six-period , crossover study was carried out as a 24-h isoglycemic clamp ( 7.2 mmol/l ) in 12 type 1 diabetic patients . RESULTS Duration of action for insulin detemir was dose dependent and varied from 5.7 , to 12.1 , to 19.9 , to 22.7 , to 23.2 h for 0.1 , 0.2 , 0.4 , 0.8 , and 1.6 units/kg , respectively . Interpolation of the dose-response relationships for AUC(GIR ) ( area under the glucose infusion rate curve ) revealed that a detemir dose of 0.29 units/kg would provide the same effect as 0.3 IU/kg NPH but has a longer duration of action ( 16.9 vs. 12.7 h , respectively ) . Lower between-subject variability was observed for insulin detemir on duration of action ( 0.4 units/kg insulin detemir vs. 0.3 IU/kg NPH , P < 0.05 ) and GIR(max ) ( maximal glucose infusion rate ) ( 0.2 and 0.4 units/kg insulin detemir vs. 0.3 IU/kg NPH , both P < 0.05 ) . Assessment of endogenous glucose production ( EGP ) and peripheral glucose uptake ( PGU ) result ed in an AOC(EGP ) ( area over the EGP curve ) of 636 mg/kg ( 95 % CI 279 - 879 ) vs. 584 ( 323 - 846 ) and an AUC(PGU ) ( area under the PGU curve ) of 173 ( 47 - 316 ) vs. 328 ( 39 - 617 ) for 0.29 units/kg detemir vs. 0.3 IU/kg NPH , respectively . CONCLUSIONS This study shows that insulin detemir provides a flat and protracted pharmacodynamic profile OBJECTIVE Glycemic control using inhaled , dry-powder insulin plus a single injection of long-acting insulin was compared with a conventional regimen in patients with type 2 diabetes , which was previously managed with at least two daily insulin injections . RESEARCH DESIGN AND METHODS Patients were r and omized to 6 months ' treatment with either premeal inhaled insulin plus a bedtime dose of Ultralente ( n = 149 ) or at least two daily injections of subcutaneous insulin ( mixed regular/NPH insulin ; n = 150 ) . The primary efficacy end point was the change in HbA1c from baseline to the end of study . RESULTS HbA1c decreased similarly in the inhaled ( -0.7 % ) and subcutaneous ( -0.6 % ) insulin groups ( adjusted treatment group difference : -0.07 % , 95 % CI -0.32 to 0.17 ) . HbA1c < 7.0 % was achieved in more patients receiving inhaled ( 46.9 % ) than subcutaneous ( 31.7 % ) insulin ( odds ratio 2.27 , 95 % CI 1.24 - 4.14 ) . Overall hypoglycemia ( events per subject-month ) was slightly lower in the inhaled ( 1.4 events ) than in the subcutaneous ( 1.6 events ) insulin group ( risk ratio 0.89 , 95 % CI 0.82 - 0.97 ) , with no difference in severe events . Other adverse events , with the exception of increased cough in the inhaled insulin group , were similar . No difference in pulmonary function testing was seen . Further studies are underway to assess tolerability in the longer term . Insulin antibody binding increased more in the inhaled insulin group . Treatment satisfaction was greater in the inhaled insulin group . CONCLUSIONS Inhaled insulin appears to be effective , well tolerated , and well accepted in patients with type 2 diabetes and provides glycemic control comparable to a conventional subcutaneous regimen Aim : This r and omized , single‐centre , double‐blind , crossover study compared the pharmacodynamic and pharmacokinetic properties of two different doses of insulin glulisine ( glulisine ) and insulin lispro ( lispro ) in lean to obese subjects Among the more than 20 million Americans who have diabetes , approximately 30 % of the cases are undiagnosed ( 1 ) . An additional 42 million people in the United States have pre-diabetes ( impaired glucose tolerance [ IGT ] , impaired fasting glucose , or both ) , a condition that often leads to diabetes if it is not treated ( 1 ) . The dramatic 41 % increase in prevalence of diabetes during the 1990s was characterized by a shift to a younger age at onset . The prevalence of diabetes increased more than 70 % in the age-group 30 to 39 years ( 1 ) . The longer the duration of poorly controlled diabetes , the greater the risk for development of vascular complications , including retinopathy , end-stage kidney disease , neuropathy , and coronary artery disease . These complications are not only debilitating but also expensive . In 2002 , health-care costs for diabetes in the United States surpassed $ 132 billion ( 1 ) . These costs were primarily related to the treatment and consequences of complications of diabetes ( 2 ) . Several large prospect i ve studies have shown that intensive treatment of diabetes can decrease the chronic complications associated with this disease ( 3 - 6 ) . There seems to be no glycemic threshold for reduction of complications ; the lower the hemoglobin A1c ( A1C ) level , the lower the rate of occurrence of diabetes-related complications ( 7 ) . Advances in pharmacologic therapies and new treatment technologies can facilitate reduction of blood glucose values in patients with diabetes to near-normal and achieve glycemic goal levels recommended in current practice guidelines . Nevertheless , the management of patients with diabetes in the United States has actually worsened during the past decade ( 8) . Data from the National Health and Nutrition Examination Survey III in 1994 showed that only 44 % of patients with type 2 diabetes achieved an A1C level of less than 7 % ( 9 ) . By the year 2000 , this proportion actually decreased to 37 % ( 10 ) . Recently , at an American Association of Clinical Endocrinologists ( AACE ) meeting , a report on the state of diabetes health showed that , in a study of 157,000 Americans in 39 states , two-thirds of the subjects with type 2 diabetes had A1C values above the American College of Endocrinology ( ACE ) goal for glycemic control of 6.5 % or less ( American College of Endocrinology/ American Association of Clinical Endocrinologists . State of Diabetes in America : Striving for Better Control . Available at : http://www.aace.com/pub/StateofDiabetes/ stateofdiabetes.php ) . Clearly , more aggressive and comprehensive application of these available treatment options , supported by diabetes education , is needed . On January 31 , 2005 , ACE and AACE convened a 2day consensus conference to review current research and address questions relevant to the treatment of diabetes . The conference brought together US and international diabetes research ers , clinical and educational experts , and ACE/AACE CONSENSUS CONFERENCE ON THE IMPLEMENTATION OF OUTPATIENT MANAGEMENT OF DIABETES MELLITUS : CONSENSUS CONFERENCE OBJECTIVE This study compares the time-action profile of inhaled insulin ( INH ; Exubera ) with that of subcutaneously injected insulin lispro ( ILP ) or regular human insulin ( RHI ) in healthy volunteers . RESEARCH DESIGN AND METHODS In this open-label , r and omized , three-way , crossover study , 17 healthy male volunteers were given each of the following treatments in r and om order : INH ( 6 mg ) , ILP ( 18 units ) , or RHI ( 18 units ) . Glucose infusion rates and serum insulin concentrations were monitored over 10 h. RESULTS INH had a faster onset of action than both RHI and ILP , as indicated by shorter time to early half-maximal effect ( 32 vs. 48 and 41 min , respectively ; P < 0.001 for IHN vs. RHI and P < 0.05 for IHN vs. ILP ) . Time to maximal effect was comparable between INH and ILP ( 143 vs. 137 min ; NS ) but was shorter for INH than RHI ( 193 min ; P < 0.01 ) . The maximal metabolic effect of INH was comparable with RHI but lower than ILP ( 8.7 vs. 9.8 vs. 11.2 mg . kg(-1 ) . min(-1 ) , respectively ; P < 0.01 for INH vs. ILP ) . The duration of action of INH , indicated by time to late half-maximal effect ( 387 min ) , was longer than ILP ( 313 min ; P < 0.01 ) and comparable to RHI ( 415 min ; NS ) . Total glucodynamic effect after inhalation of INH was comparable to both ILP and RHI ( NS ) . Relative bioefficacy of INH was 10 % versus RHI and 11 % versus ILP . No drug-related adverse events were observed . CONCLUSIONS INH had a faster onset of action than RHI or ILP and a duration of action longer than ILP and comparable to RHI . These characteristics suggest that inhaled insulin is suitable for pr and ial insulin supplementation in patients with diabetes Several studies have suggested that diabetes mellitus may alter the risk of developing a variety of cancers , and the associations are biologically plausible . To learn more about the relation between diabetes and cancer mortality , the authors examined associations with selected cancers in a large , prospect i ve US cohort of 467,922 men and 588,321 women who had no reported history of cancer at enrollment in 1982 . After 16 years of mortality follow-up , diabetes was significantly associated with fatal colon cancer in men ( multivariate relative risk ( RR ) = 1.20 , 95 % confidence interval ( CI ) : 1.06 , 1.37 ) and women ( RR = 1.24 , 95 % CI : 1.07 , 1.43 ) and with pancreatic cancer in men ( RR = 1.48 , 95 % CI : 1.27 , 1.73 ) and women ( RR = 1.44 , 95 % CI : 1.21 , 1.72 ) . For men , diabetes was significantly associated with liver cancer ( RR = 2.19 , 95 % CI : 1.76 , 2.72 ) and bladder cancer ( RR = 1.43 , 95 % CI : 1.14 , 1.80 ) . In addition , diabetes was significantly associated with breast cancer in women ( RR = 1.27 , 95 % CI : 1.11 , 1.45 ) . These associations were not explained by high body mass . Our findings suggest that diabetes is an independent predictor of mortality from cancer of the colon , pancreas , female breast , and , in men , of the liver and bladder 94 diabetic patients established on treatment with porcine ( n = 47 ) or bovine ( n = 47 ) insulin took part in a double-blind crossover trial , in which 6-week periods of treatment with the appropriate animal insulin were compared with periods of treatment with biosynthetic human insulin ( BHI ) . 6 patients withdrew during the trial , in 3 cases because of hypoglycaemia while taking BHI . In bovine-insulin-treated patients , the mean glucose level ( mean of seven capillary-blood sample s over 1 day ) , the modified M index , and total daily insulin requirement were the same on BHI and bovine-insulin treatment . For porcine-insulin-treated patients , mean glucose level and the modified M index were slightly higher on BHI than on porcine-insulin treatment ( 9.7 vs 9.0 mmol/l and 79.6 vs 65.0 , respectively ) , despite an average increase of 2.3 units/day of BHI after 6 weeks of such treatment . Hypoglycaemic episodes were not significantly more or less frequent on BHI in either group of patients . In both groups fasting blood glucose was higher during BHI treatment than during animal-insulin treatment ( 14.2 vs 12.8 mmol/l [ bovine group ] ; 12.1 vs 9.6 mmol/l [ porcine group ] ) . In bovine-insulin-treated patients blood glucose before the evening insulin injection was higher on BHI than on bovine insulin ( 11.6 vs 10.0 mmol/l ) . BHI appears to be a safe alternative to porcine or bovine insulin . Differences in the pharmacokinetics of BHI may account for the observed differences in blood-glucose responses OBJECTIVE The aim of this study was to determine whether premeal pulmonary delivery of rapid-acting , dry-powder insulin ( Exubera ) plus Ultralente could provide glycemic control comparable to a conventional insulin regimen in type 1 diabetes . RESEARCH DESIGN AND METHODS Three hundred thirty-five subjects were r and omly assigned to receive either premeal inhaled insulin plus bedtime Ultralente or two to three injections of regular and NPH insulin for 24 weeks . The primary end point was a change in HbA(1c ) . RESULTS Mean decreases in HbA(1c ) values were comparable for inhaled ( 8.1 - 7.9 % ) and conventional groups ( 8.1 - 7.7 % ) ( adjusted treatment group difference 0.16 % [ 95 % CI -0.01 to 0.32 ] ) . There were greater reductions for inhaled versus conventional regimen in fasting and postpr and ial plasma glucose ( adjusted mean change differences -25.17 and -30.28 mg/dl , respectively [ 95 % CI -43.39 to -6.95 and -54.58 to -5.97 , respectively ] ) . Hypoglycemia ( events/subject month ) was lower for the inhaled ( 8.6 ) versus the conventional ( 9.0 ) group ( risk ratio , 0.96 [ 95 % CI 0.93 - 0.99 ] ) . In subjects receiving inhaled insulin , increased insulin antibody levels were observed , but there were no associated clinical or laboratory changes . Adverse events were comparable between groups . Mild to moderate cough was more frequent in the inhaled insulin group ( 27 vs. 5 % ) but decreased during the treatment . Pulmonary function tests were not different between the groups except for a greater decrease in carbon monoxide diffusing capacity in the inhaled insulin group . Treatment satisfaction was greater in the inhaled than in the conventional group . CONCLUSIONS Inhaled insulin is effective , well tolerated , and well accepted in patients with type 1 diabetes and provides glycemic control comparable to that with a conventional insulin regimen OBJECTIVE Human regular U-500 ( U-500R ) insulin ( 500 units/mL ) is increasingly being used clinical ly , yet its pharmacokinetics ( PK ) and pharmacodynamics ( PD ) have not been well studied . Therefore , we compared PK and PD of clinical ly relevant doses of U-500R with the same doses of human regular U-100 ( U-100R ) insulin ( 100 units/mL ) . RESEARCH DESIGN AND METHODS This was a single-site , r and omized , double-blind , crossover euglycemic clamp study . Single subcutaneous injections of 50- and 100-unit doses of U-500R and U-100R were administered to 24 healthy obese subjects . RESULTS Both overall insulin exposure ( area under the serum insulin concentration versus time curve from zero to return to baseline [ AUC0-t ’ ] ) and overall effect ( total glucose infused during a clamp ) were similar between formulations at both 50- and 100-unit doses ( 90 % [ CI ] of ratios contained within [ 0.80 , 1.25 ] ) . However , peak concentration and effect were significantly lower for U-500R at both doses ( P < 0.05 ) . Both formulations produced relatively long duration s of action ( 18.3 to 21.5 h ) . Time-to-peak concentration and time to maximum effect were significantly longer for U-500R than U-100R at the 100-unit dose ( P < 0.05 ) . Time variables reflective of duration of action ( late tRmax50 , tRlast ) were prolonged for U-500R versus U-100R at both doses ( P < 0.05 ) . CONCLUSIONS Overall exposure to and action of U-500R insulin after subcutaneous injection were no different from those of U-100R insulin . For U-500R , peaks of concentration and action profiles were blunted and the effect after the peak was prolonged . These findings may help guide therapy with U-500R insulin for highly insulin-resistant patients with diabetes OBJECTIVE To compare the efficacy and safety of the rapid-acting insulin analog glulisine and regular insulin in hyperglycemic hospitalized patients . RESEARCH DESIGN AND METHODS A total of 180 hospitalized patients with type 2 diabetes received either glulisine ( n = 88 ) or regular insulin ( n = 92 ) before each meal in combination with insulin glargine at bedtime in a r and omized double-blind fashion . All previous diabetes medications were discontinued if applicable . Doses of insulin were adjusted to obtain target blood glucose concentrations of < 130 mg/dl before meals and at bedtime while avoiding hypoglycemia . RESULTS Overall mean blood glucose concentrations were ∼8 mg/dl lower in the glulisine group than in the regular insulin group ( 152.6 ± 66.6 vs. 160.4 ± 70.8 mg/dl ; P < 0.0002 ) . This improvement was wholly due to ∼22 mg/dl lower levels after 4 days of therapy ( 140 ± 55 vs. 162 ± 71 mg/dl ; P < 0.0007 ) ; after day 4 , this difference progressively increased such that mean blood glucose concentrations from day 7 onward were ∼31 mg/dl lower in the glulisine group . The mean daily incidence of hypoglycemia was slightly but not significantly lower in the glulisine than the regular insulin group ( 0.10 ± 0.02 vs. 0.14 ± 0.03 episode/day ; P > 0.35 ) . CONCLUSIONS In hospitalized type 2 diabetic patients , glulisine may provide better glycemic control than regular insulin , especially in those who have a prolonged length of stay To compare the pharmacokinetics/dynamics of the long-acting insulin analog glargine with NPH , ultralente , and continuous subcutaneous ( SC ) infusion of insulin lispro ( continuous subcutaneous insulin infusion [ CSII ] ) , 20 C-peptide-negative type 1 diabetic patients were studied on four occasions during an isoglycemic 24-h clamp . Patients received SC injection of either 0.3 U/kg glargine or NPH insulin ( r and om sequence , crossover design ) . On two subsequent occasions , they received either an SC injection of ultralente ( 0.3 U/kg ) or CSII ( 0.3 U x kg(-1 ) x 24 h(-1 ) ) ( r and om sequence , crossover design ) . After SC insulin injection or CSII , intravenous ( IV ) insulin was tapered , and glucose was infused to clamp plasma glucose at 130 mg/dl for 24 h. Onset of action ( defined as reduction of IV insulin > 50 % ) was earlier with NPH ( 0.8 + /- 0.2 h ) , CSII ( 0.5 + /- 0.1 h ) , and ultralente ( 1 + /- 0.2 h ) versus glargine ( 1.5 + /- 0.3 h ) ( P < 0.05 ) ( mean + /- SE ) . End of action ( defined as an increase in plasma glucose > 150 mg/dl ) occurred later with glargine ( 22 + /- 4 h ) than with NPH ( 14 + /- 3 h ) ( P < 0.05 ) but was similar with ultralente ( 20 + /- 6 h ) . NPH and ultralente exhibited a peak concentration and action ( at 4.5 + /- 0.5 and 10.1 + /- 1 h , respectively ) followed by waning , whereas glargine had no peak but had a flat concentration/action profile mimicking CSII . Interindividual variability ( calculated as differences in SD of plasma insulin concentrations and glucose infusion rates in different treatments ) was lower with glargine than with NPH and ultralente ( P < 0.05 ) but was similar with glargine and CSII ( NS ) . In conclusion , NPH and ultralente are both peak insulins . Duration of action of ultralente is greater , but intersubject variability is also greater than that of NPH . Glargine is a peakless insulin , it lasts nearly 24 h , it has lower intersubject variability than NPH and ultralente , and it closely mimics CSII , the gold st and ard of basal insulin replacement Aims : A multinational , r and omized , double-blind , two-way crossover trial to compare the pharmacokinetic and pharmacodynamic properties of bolus , subcutaneously administered insulin glulisine ( glulisine ) and insulin aspart ( aspart ) in insulin-naÏve , obese subjects with type 2 diabetes . Methods : Thirty subjects [ 9/21 females/males ; mean ± SD age : 60.7 ± 7.7 years ; body mass index ( BMI ): 33.5 ± 3.3 kg/m2 ; duration of diabetes : 6.8 ± 4.6 years ; HbA1c : 7.1 ± 0.8 % ] were included in the analysis . They fasted overnight and then received a 0.2 U/kg subcutaneous dose of glulisine or aspart 2 min before starting a st and ardized test meal , 7 days apart , according to a r and omization schedule . Blood sample s were taken every 15 min , starting 20 min before the meal and ending 6 h postpr and ially . Results : The area under the absolute glucose concentration – time curve between 0 and 1 h after insulin injection and maximal glucose concentration was significantly lower with glulisine than with aspart ( p = 0.0455 and 0.0337 , respectively ) . However , for the total study period , plasma glucose concentration was similar for glulisine and aspart . Peak insulin concentration was significantly higher for glulisine than for insulin aspart ( p < 0.0001 ) . Hypoglycaemic events ( ≤ 70 mg/dl with or without symptoms ) occurred in 13 and 16 subjects treated with glulisine and aspart , respectively , but there were no cases of severe hypoglycaemia requiring intervention . Conclusions : Glulisine was associated with lower glucose levels during the first hour after a st and ard meal ; the remaining glucose profiles were otherwise equivalent , with higher insulin levels observed throughout the study period OBJECTIVE To determine the subcutaneous absorption rates and the appearance in plasma of 3 formulations of the long-acting human insulin analog insulin glargine ( HOE 901 ) differing only in zinc content ( 15 , 30 , and 80 microg/ml ) . RESEARCH DESIGN AND METHODS We conducted 2 studies . Study 1 compared the subcutaneous abdominal injection of 0.15 U/kg of 125I-labeled insulin glargine[15 ] , insulin glargine[80 ] , NPH insulin , and placebo . In study 2 , 0.2 U/kg of insulin glargine[30 ] was injected into the arm , leg , and abdominal regions . Both studies had a r and omized crossover design ; each enrolled 12 healthy men , aged 18 - 50 years . RESULTS In study 1 , the time in hours for 25 % of the administered radioactivity to disappear after bolus subcutaneous injection ( T75 % ) for NPH insulin indicated a significantly faster absorption rate compared with the 2 insulin glargine formulations ( 3.2 vs. 8.8 and 11.0 h , respectively P < 0.0001 ) . Mean residual radioactivity with NPH insulin was also significantly lower at 24 h ( 21.9 vs. 43.8 and 52.2 % , P < 0.0001 ) . The calculated plasma exogenous insulin concentrations after NPH insulin were substantially higher than those with insulin glargine , reaching a peak within the first 6 h after administration before declining . Insulin glargine , however , did not exhibit a distinct peak . Weighted average plasma glucose concentration between 0 and 6 h was significantly lower after NPH compared with insulin glargine ( P < 0.001 ) . In study 2 , there were no significant differences in the absorption characteristics of insulin glargine between the 3 injection sites ( T75 % = 11.9 , 15.3 , and 13.2 h for arm , leg , and abdomen , respectively ) or in residual radioactivity at 24 h. CONCLUSIONS Subcutaneous absorption of insulin glargine is delayed compared with NPH insulin . There is little or no difference in the absorption rate of insulin glargine between the main subcutaneous injection sites OBJECTIVE To compare glycemic control obtained with the new rapid-acting insulin analog insulin aspart with that obtained with unmodified human insulin using algorithm-driven dosage adjustment . RESEARCH DESIGN AND METHODS This was a multicenter r and omized double-blind crossover study of 90 male subjects with type 1 diabetes . Insulin aspart or soluble human insulin was administered before meals , and NPH insulin was administered at bedtime as basal therapy . Each 4-week study period ended with a 24-h inpatient serum insulin and plasma glucose profile . RESULTS The 24-h plasma glucose control obtained with insulin aspart , as assessed by excursions of blood glucose outside a predefined normal range ( 4.0 - 7.0 mmo/l ) , was superior ( 22 % reduction in excursion , P < 0.01 ) . Fructosamine levels remained unchanged with insulin aspart , with daytime glycemic control superior but nighttime glycemic control inferior . Eight-point home blood glucose profiles confirmed that insulin aspart significantly improved postpr and ial blood glucose control after lunch and dinner ( P < 0.05 ) without deterioration of prepr and ial blood glucose control . Hypoglycemic episodes requiring third-party intervention were significantly fewer with insulin aspart than with human insulin ( 20 vs. 44 events , P < 0.002 ) . Insulin aspart was well tolerated . CONCLUSIONS In comparison with human insulin , insulin aspart can improve postpr and ial glycemic control as assessed by a reduction in hyper- and hypoglycemic excursions in people with type 1 diabetes . For its full potential to be realized , it will need to provide better control of nighttime hyperglycemia OBJECTIVE The rapid-acting insulin analogs aspart and lispro have now been developed in biphasic formulations . This trial compared the postpr and ial serum glucose control of biphasic insulin aspart 30 ( BIAsp 30 : 30 % aspart , 70 % protaminated aspart ) with that of biphasic insulin lispro 25 ( Mix25 : 25 % lispro , 75 % protaminated lispro ) and biphasic human insulin 30 ( BHI 30 : 30 % regular insulin , 70 % NPH insulin ) in insulin-treated subjects with type 2 diabetes . RESEARCH DESIGN AND METHODS This was an open-labeled , r and omized , single-dose , three-way crossover trial of 61 insulin-treated subjects with type 2 diabetes who had no significant late diabetic complications . BIAsp 30 and Mix25 were injected subcutaneously immediately before a test meal , and BHI 30 was injected 15 min before a test meal . The primary target of analysis was serum glucose excursion 0 - 5 h after a meal . RESULTS The postpr and ial glycemic control with BIAsp 30 , as assessed by the 5-h postmeal serum glucose excursion , was superior to that with both BHI 30 and Mix25 ( 16.6 + /- 4.5 vs. 20.1 + /- 4.9 and 18.9 + /- 6.1 mmol/l per hour , respectively ; P < 0.001 and P < 0.05 ) . For BIAsp 30 versus BHI 30 , this was supported by a reduced maximum glucose concentration [ C(max(SG ) ) ] ( -5 % ; P < 0.05 ) occurring earlier ( -13 min ; P < 0.01 ) . Furthermore , BIAsp 30 displayed a higher maximum serum insulin concentration ( + 101 % ; P < 0.001 ) occurring earlier ( -55 min ; P < 0.001 ) compared with BHI 30 . Compared with Mix25 , there was a shorter time to C(max(SG ) ) ( -11 min ; P < 0.05 ) after treatment with BIAsp 30 . CONCLUSIONS This trial demonstrates that BIAsp 30 improves postpr and ial glycemic control compared with both Mix25 and BHI 30 in subjects with type 2 diabetes OBJECTIVE To see if insulin glargine improves glycemic control in a clinical setting . RESEARCH DESIGN AND METHODS A question naire and electronic data base were used to assess glycemic parameters for 292 type 1 diabetic subjects taking > or = 4 injections per day and receiving glargine as their only long-acting basal insulin for at least 6 months . Sixty-three subjects were taking glargine in the morning , 125 were taking glargine in the evening , and 104 were splitting the glargine dose between the morning and evening . RESULTS The mean ( + /-S.D. ) age and duration of diabetes were 32 + /- 10 years and 15.9 + /- 10.3 years , respectively . The mean ( + /-S.E.M. ) duration s of treatment with glargine were 13.1 + /- 0.6 months , 12.2 + .- 0.4 months , and 14.3 + /- 0.5 months for the morning , evening , and split treatment groups , respectively ( P < 0.01 ) . The A1C values improved significantly from baseline for the evening and the split dosage groups or when all groups were combined . The mean basal insulin dose was significantly reduced at the end of the study in all the three groups from baseline with no change in the short-acting insulin dose . The number of severe hypoglycemic episodes decreased from 379 in the year prior to glargine treatment to 167 in the post-glargine year . The weight gain was significantly higher in the group that took the split glargine dose ( P < 0.01 ) . CONCLUSIONS Similar or improved glycemic control was achieved by administering glargine in the morning , evening , or using a split dose without any further increase in severe hypoglycemic episodes . Splitting the glargine dose did not offer any advantages in glycemic control parameters Insulin aspart ( IAsp ) , is a rapid-acting analogue of human insulin ( HI ) , for use in the meal related treatment of diabetes mellitus . The degree of glycaemic control achieved by IAsp in comparison with HI after algorithm-driven dose optimisation was tested over 3 months . The prospect i ve , multicentre , r and omised , open-label study with parallel groups was performed in 48 centres in 11 countries and included 423 basal-bolus treated patients with Type 1 diabetes . Main outcome measures were blood glucose control assessed by HbA1c , nine-point self-monitored blood glucose profiles , insulin dose , quality of life , hypoglycaemia and adverse events . An algorithm-driven increase occurred in the dose and number of daily injections of basal insulin , particularly in the IAsp group . After 12 weeks of treatment , HbA1c was significantly lower in IAsp compared to HI treated subjects by 0.17 ( 95 % CI 0.30 - 0.04 ) ( P<0.05 ) . Comparison of the blood glucose profiles showed lower blood glucose levels with IAsp after breakfast ( mean 8.4 vs 10.1 mmol/l ; P<0.0001 ) and dinner ( 8.2 vs 9.3 mmol/l ; P<0.01 ) . There were no differences between treatments in the incidence of hypoglycaemic episodes or in the adverse event profiles . The WHO Diabetes Treatment Satisfaction Question naire score for perceived hyperglycaemia was lower with Iasp ( P=0.005 ) , and patients found the insulin aspart treatment more flexible ( P=0.022 ) . The current study underlines the need for optimising the basal insulin regimen in order to take full advantage of the pharmacodynamics of IAsp BACKGROUND AND AIMS Once-daily ( OD ) basal insulin glargine ( GLA ) can be used as part of a multiple daily injection regimen in patients with type 1 diabetes mellitus . This r and omized , multicenter study compared GLA+pr and ial regular human insulin ( RHI ) with GLA+pr and ial insulin lispro ( LIS ) in reducing the incidence of severe nocturnal hypoglycemia at endpoint . In addition , the effects on glycemic control of both treatments were investigated . METHODS AND RESULTS Patients ( 489 ) previously on neutral protamine Hagedorn ( NPH ) insulin or GLAR plus RHI/LIS were switched to , or continued on GLA ( target fasting blood glucose [FBG]=5.0 - 6.7 mmol/L [ 90 - 120 mg/dL ] ) for 8 weeks ( qualification phase ) prior to r and omization ; patients continued with their previous bolus insulin . Patients ( n=395 ) were then r and omized to LIS ( n=193 ) or RHI ( n=202 ) and treated for 16 weeks . The proportion of patients experiencing severe nocturnal hypoglycemia at the end of the study was 1.55 % ( n=3 ) in the RHI group and 1.11 % ( n=2 ) in the LIS group ( p=0.938 between groups ) ; the mean difference was 0.44 % ( 95 % CI : -1.77 , 2.21 ) , suggesting non-inferiority of RHI versus LIS . At the end of the study , both treatments did not differ with respect to glycemic control , as measured by hemoglobin A(1c ) and FBG . CONCLUSION These results suggest that GLA+LIS and GLA+RHI treatments were associated with a similar and low rate of severe nocturnal hypoglycemia . Further studies with greater patient sizes are necessary to verify the findings from the current study Abstract Objective : The pharmacokinetics of a new insulin analogue , insulin aspart , were compared with unmodified human insulin in a double-blind crossover study of 25 fasting healthy men following a single subcutaneous dose . Methods : Either insulin aspart or human insulin , 0.1 U · kg-body-weight−1 , was injected subcutaneously and followed by determination of 8-h profiles of serum insulin and plasma glucose concentrations . Results : The absorption of insulin aspart was , on average , more than twice as fast and reached levels more than twice as high compared with human insulin [ tmax(ins ) of 52 ( 23 ) vs 145 ( 93 ) min , P < 0.0001 ; and Cmax(ins ) of 41 ( 11 ) vs 18 ( 4 ) mU · l−1 , P < 0.0001 ; mean with ( SD ) ] . However , total bioavailability did not differ between the insulins , and thus the mean residence time was significantly shorter for insulin aspart [ MRT(ins ) of 149 ( 26 ) vs 217 ( 30 ) min , P < 0.0001 ] . Plasma glucose ( PG ) fell more than twice as rapidly [ tmin(PG ) of 94 ( 45 ) vs 226 ( 120 ) min , P < 0.0001 ] , to a greater extent [ Cmin(PG ) 2.1 ( 0.6 ) vs 1.4 ( 0.4 ) mmol · l−1 , P < 0.0001 ] , and for a shorter duration with insulin aspart than with human insulin . Conclusion : With improved subcutaneous absorption characteristics , the insulin aspart concentration – time profile resembles physiological meal-stimulated insulin release more closely than that of unmodified human insulin . This significantly alters the pharmacodynamic response in an advantageous manner in the meal-related treatment of diabetes mellitus OBJECTIVE To study the pharmacodynamic properties of a 30/70 premixed formulation of the rapid-acting insulin analog insulin aspart ( B28Asp ) and its protamine-retarded preparation ( 30/70 IA ) in comparison with a respective mixture of soluble human insulin and NPH insulin ( 30/70 HI ) . RESEARCH DESIGN AND METHODS In this single-center double-blind euglycemic glucose-clamp study , 24 healthy male volunteers ( age , 26 ± 2 years ; BMI , 23.7 ± 1.7 kg/m2 ) received single subcutaneous injections of 0.3 U/kg body wt of either 30/70 IA or 30/70 HI on 2 study days in r and omized order . Glucose infusion rates ( GIRs ) were determined over a 24-h period after administration . RESULTS The injection of 30/70 IA result ed in an earlier onset and more pronounced peak of action ( tmax , 127 ± 24 min ; GIRmax 9.7 ± 2.3 mg · kg−1 · min−1 ) than 30/70 HI ( tmax , 185 ± 52 min ; GIRmax , 7.4 ± 1.7 mg · kg−1 · min−1 _ ( P < 0.001 ) . The metabolic activity of 30/70 IA ( measured as the sum of the glucose infused ) within the first 4 h after injection was 37 % > that of 30/70 HI ( P < 0.0001 ) , while the total metabolic potencies over 24 h of both preparations were comparable . CONCLUSIONS The 30/70 premixed formulation of insulin aspart shows a significantly greater metabolic effect in the first 4 h after subcutaneous injection than the 30/70 mixture of human insulin . Insulin aspart retains its pharmacodynamic properties in a premixed 30/70 formulation AIM The objective of the study was to establish the dose response of IN-105 tablets and explore a possible therapeutic window in type 2 diabetes subjects poorly controlled on metformin . METHODS The primary objective was to examine the effect of sequential single ascending doses of IN-105 on the plasma glucose concentration under fed conditions . All subjects received , sequentially , matching placebo , 10 , 15 , 20 and 30 mg IN-105 tablets in five consecutive periods . Tablets were administered 20 min prior to meal in all the periods . Plasma levels of immunoreactive insulin , C-peptide and glucose were measured up to 180 min from the time of dosing . The changes in postpr and ial glucose levels at 120 min in response to IN-105 administration were also compared against those of placebo . RESULTS Changes in glucose from baseline ( mean + /- s.d . ) at 140 min ( 2 h postpr and ial ) were 94.84 + /- 22.3 , 79.45 + /- 43.00 , 70.68 + /- 35.71 , 63.47 + /- 42.75 and 53.06 + /- 47.27 mg/dL , respectively , and exhibited linear dose-response . The insulin C(max ) values were found to be 50.8 + /- 26.0 mU/L for placebo , 100.3 + /- 66.7 with 10 mg IN-105 , 177.69 + /- 150.3 with 15 mg IN-105 , 246.2 + /- 245.2 with 20 mg IN-105 and 352.5 + /- 279.3 mU/L with 30 mg of IN-105 . CONCLUSIONS IN-105 absorption is proportional to the dose administered . The 2-h postpr and ial glucose excursion was reduced in a dose proportional manner . Circulating C-peptide levels were found to be suppressed in proportion to the IN-105 exposure . IN-105 reduces glucose excursion despite lower endogenous insulin secretion . IN-105 seems to have a wide therapeutic window as no clinical hypoglycaemia was observed at any of the doses studied . Semisynthetic human insulin ( Novo ) was compared with porcine insulin with regard to absorption from subcutaneous depots , blood glucose control and plasma insulin concentrations in patients , and the binding to insulin receptors of porcine and human origin . The binding affinities of semisynthetic human insulin and porcine insulin were identical with human erythrocyte receptors and receptors on porcine hepatocytes . The subcutaneous absorption of semisynthetic human and porcine 125I-labelled insulin both of soluble and lente type was identical . The metabolic control study was performed as a double-blind crossover study in eight type I diabetics . They received semisynthetic human insulin and porcine insulin ( of soluble as well as lente type ) for 10 days each , the last 7 days in each period being the observation period . Blood glucose concentration was measured 9 times per 24 hours . No statistically significant differences were found between mean blood glucose levels at the 9 samplings or in the overall mean blood glucose concentration . Further , the blood glucose control was evaluated as a function of time by a computerized method for time series analysis of a complex dynamic system . This method described adequately each blood glucose value as a linear function of the immediately preceding blood glucose value and that measured 24 hours before . No difference was found between human and porcine insulin when the blood glucose control was assessed by this method . Plasma concentrations of total insulin ( IRI ) and free IRI before and 3 hours after the morning insulin injection were identical in the two treatment periods . It is concluded that human and porcine insulin can be interchanged in the treatment of diabetics without changing the dose OBJECTIVE To study the pharmacokinetic and pharmacodynamic profile of insulin aspart ( a new fast-acting human insulin analog ) after subcutaneous administration in the deltoid , abdominal , and thigh sites and to compare this profile with regular human insulin ( Novolin ; Novo Nordisk A/S , Copenhagen ) . RESEARCH DESIGN AND METHODS A total of 20 healthy subjects were studied in a single-center six-period double-blind r and omized crossover trial with 6 study days and a washout period of 1 week between each single daily dose of the trial drug . Subjects were r and omized to receive a single dose of 0.2 U/kg of insulin aspart or regular insulin on each of the 6 study days in three different sites ( the deltoid , the abdomen , and the thigh ) during a 10-h euglycemic clamp ( two drugs and three injection sites ) . Pharmacokinetic and pharmacodynamic measurements were derived from blood sample measurements of glucose , insulin , and C-peptide during these clamps . RESULTS The pharmacodynamic data from the euglycemic clamp study showed that , regardless of injection site , the maximal glucose infusion rate ( GIR Cmax ) was greater and occurred at an earlier time ( GIR Tmax ) after administration of insulin aspart than regular insulin ( GIR Cmax : abdomen 813 vs. 708 , deltoid 861 vs. 736 , and thigh 857 vs. 720 g/min , P < 0.05 for all ; GIR Tmax : abdomen 94 vs. 173 , deltoid 111 vs. 192 , and thigh 145 vs. 193 g/min , P < 0.05 for all ) . Pharmacokinetic parameters were also consistent with faster absorption and higher peak insulin concentrations after insulin aspart administration . From all sites , the peak insulin concentration ( Cmax ) was higher and occurred earlier ( Tmax ) after administration of insulin aspart than of regular insulin ( Cmax : abdomen 501 vs. 260 , deltoid 506 vs. 252 , thigh 422 vs. 220 pmol/l , P < 0.001 for all sites ; Tmax : abdomen 52 vs. 109 , deltoid 54 vs. 98 , and thigh 60 vs. 107 min , P < 0.01 for all sites ) . The absorption and glucose-lowering action of insulin aspart did not differ between sites ( similar GIR Cmax , Tmax , and area under the curve parameters ) . However , the duration of the glucose-lowering effect was up to 34 min shorter ( P < 0.01 ) for the abdomen injections than for the deltoid or thigh injections ( lower time of 50 % glucose disposal ) . In addition , the amount of glucose infused was significantly lower by 10 - 14 % in the abdomen than in other sites . CONCLUSIONS Subcutaneous administration of insulin aspart causes a more rapid and intense maximal effect compared with regular insulin during euglycemic clamp studies in nondiabetic subjects . Abdominal administration of insulin aspart has a shorter duration of glucose-lowering effect compared with administration in the deltoid or thigh Epidemiologic evidence suggests diabetic men have a slightly lower prostate cancer risk than non-diabetic men . We examined this association in a prospect i ve cohort study of 35 239 men , 50–76 years old , in Washington State who completed a baseline question naire between 2000 and 2002 . Incident prostate cancers as of 31 December 2004 were identified through the SEER registry . Diabetic men had a slightly lower risk of prostate cancer than non-diabetic men ( hazard ratio ( HR ) 0.83 , 95 % confidence interval ( CI ) 0.64–1.07 ) . Insulin users overall and insulin users with diabetic complications had decreased risks , compared to non-diabetic men ( HR 0.49 , 95 % CI 0.26–0.92 ) and ( HR 0.36 , 95 % CI 0.15–0.87 ) , respectively . Oral medication use for diabetes was not associated with prostate cancer . Insulin is likely a marker of severity of diabetes . Future studies of this association should consider diabetes type , treatment , severity , complications and biomarkers BACKGROUND Epidemiological evidence suggests that diabetes mellitus ( DM ) is associated with a decrease in risk for prostate cancer ( PCa ) . The objective of this study was to examine the association between PCa risk and several characteristics of DM ( duration , age at diagnosis , treatment ) in data from two population -based , case-control studies of PCa . METHODS PCa cases ( n = 1,752 ) , and controls ( n = 1,644 ) were residents of King County , Washington identified using the Surveillance , Epidemiology , and End Results Seattle-Puget Sound cancer registry and r and om digit dialing , respectively . The majority of PCa patients had localized stage disease ( 78 % ) . Using self-reported on DM , logistic regression was used to calculate odds ratios ( OR ) and 95 % confidence intervals ( 95 % CI ) for associations between DM characteristics and PCa risk . RESULTS After adjustment for confounding factors , DM status was not significantly associated with PCa risk ( OR = 0.98 ; 95 % CI = 0.76 - 1.27 ) . However , early-onset DM ( diagnosed before age 30 ) showed a significant inverse association with PCa risk ( OR = 0.27 ; 95 % CI = 0.07 - 0.97 ) . Time since DM diagnosis ( median = 6 years ) and DM treatment types ( i.e. , diet changes , oral medications , and insulin ) did not show significant associations with PCa risk . CONCLUSIONS These data suggest that DM is not associated with PCa risk ; however , early-onset DM , possibly reflecting insulin dependent DM ( type 1 ) , may be an important component of the previously reported inverse association between DM on PCa risk , but these findings are based on a small number of observations and require further investigation AIMS Assessment of the long-term safety and efficacy of liquid inhaled insulin via AERx insulin Diabetes Management System ( iDMS ) in a basal/bolus treatment regimen of adults with Type 1 diabetes . METHODS Patients were r and omized 2 : 1 to pr and ial inhaled ( n = 205 ) or subcutaneous ( s.c . ) ( n = 99 ) insulin , plus one/two daily injections of neutral protamine Hagedorn ( NPH ) insulin for 12 months . The primary endpoints were pulmonary function tests ( PFT ) and baseline changes in chest X-rays at 12 months . Safety and efficacy assessment s were measured at regular intervals . RESULTS PFTs after 12 months were comparable between the groups , except for reduced per cent of predicted carbon monoxide lung diffusing capacity with inhaled insulin ( difference : -2.03 % , P = 0.04 ) occurring after the first 3 months and then stabilizing . There were no apparent treatment differences in chest X-rays . Overall risk of hypoglycaemia [ risk ratio ( RR ) 1.02 , P = 0.83 ] and adverse events were comparable between groups . Risk of nocturnal hypoglycaemia was higher in the inhaled group ( RR 1.58 , P = 0.001 ) . Cough [ 10 % ( inhaled ) ; 3 % ( s.c . ) ] tended to be mild in nature . Inhaled insulin was non-inferior to s.c . insulin for change in glycated haemoglobin ( HbA(1c ) ) after 12 months [ difference 0.18 % ( CI 95%-0.04 ; 0.39 ) ] . At trial end , mean laboratory measured fasting plasma glucose was lower in the inhaled group ( inhaled 9.2 mmol/l ; s.c . 11.7 mmol/l ; difference : -2.53 mmol/l , P < 0.001 ) . CONCLUSIONS The safety and efficacy results in this trial were similar to those reported with other inhaled insulins ; however , inhaled insulin using AERx iDMS requires further optimization to reduce nocturnal hypoglycaemia before it has comparable safety and efficacy to s.c . insulin aspart BACKGROUND Many patients with poorly controlled type 2 diabetes mellitus ( DM ) receive , as initial insulin treatment , the addition of a basal formulation to an existing regimen of oral antidiabetic drug ( OAD ) therapy . Used this way , the insulin analogue detemir has been associated with improved glycemic control of a magnitude similar to neutral protamine Hagedorn ( NPH ) , with lower rates of hypoglycemia and weight gain . Initial studies investigated detemir administered BID , but pharmacologic data suggest that detemir might be effective with QD administration . OBJECTIVES The aims of this study were to compare the effectiveness and tolerability of detemir versus NPH administered QD together with > or = 1 OAD in poorly controlled type 2 DM , and to compare different administration times of detemir . METHODS This 20-week , multicenter , r and omized , open-label , 3-arm , parallel-group trial was conducted at 91 centers across Europe and the United States . Men and women were eligible for participation if they were aged > or = 18 years , had a body mass index ( BMI ) < or = 40 kg/m(2 ) , had a diagnosis of type 2 DM of at least 12 months ' duration , and were insulin naive . Eligible patients also had a glycosylated hemoglobin ( HbA(1c ) ) concentration value not outside the range of 7.5 % to 11.0 % following at least 3 months ' treatment with > or = 10 AD . Patients were r and omly assigned to receive an evening SC injection of detemir , a prebreakfast injection of detemir , or an evening injection of NPH insulin ( 1:1:1 ) , administered at initial doses of 10 IU ( U ) . RESULTS A total of 504 patients were enrolled 5 men , 219 women ; mean [ SD ] age , 59 [ 11 ] years ; mean [ SD ] BMI , 30 [ 5 ] kg/m2 ; insulin detemir before breakfast , 168 ; insulin detemir evening , 170 ; NPH insulin evening , 166 ) . The intent-to-treat population comprised 498 patients . Morning and evening detemir were associated with reductions in HbA(1c ) similar to those with evening NPH ( raw mean decreases , -1.58 % , -1.48 % , and -1.74 % , respectively ) . Nine-point profile and fasting and predinner plasma glucose data found morning detemir to be associated with a different diurnal glycemic profile compared with the evening regimens . Compared with evening NPH , 24-hour and nocturnal hypoglycemia were reduced by 53 % ( P = 0.019 ) and 65 % ( P = 0.031 ) , respectively , with evening detemir . Incidences of hypoglycemia did not differ significantly between groups that received morning and evening detemir , but nocturnal hypoglycemia was reduced further , by 87 % , with morning detemir compared with evening NPH ( P < 0.001 ) . Weight gain was 1.2 , 0.7 , and 1.6 kg with morning detemir , evening detemir , and NPH , respectively ( P = 0.005 for evening detemir vs NPH ) . No between-treatment differences were seen in other tolerability end points . CONCLUSIONS The results of this study in patients whose type 2 DM was poorly controlled with > or = 1 OAD suggest that insulin detemir QD in the morning or evening can be used to improve glycemic control . Compared with NPH , insulin detemir may offer some tolerability advantages in this role AIMS /HYPOTHESIS This study compared the pharmacokinetics and pharmacodynamics of insulin glulisine , insulin lispro , and regular human insulin in obese subjects . METHODS In this single-dose , r and omized , double-blind , crossover euglycaemic clamp study , 18 non-diabetic subjects ( mean body mass index [ BMI ] 34.7 kg . m ( -2 ) ) were r and omized to receive subcutaneous injections of each insulin ( 0.3 U . kg ( -1 ) ) in pre-determined sequences . RESULTS Insulin glulisine and insulin lispro had more rapid-acting profiles than regular human insulin . Fractional glucose infusion rate (GIR)-area under curves ( AUC ) of the GIR curve and maximum GIR were greater for insulin glulisine and insulin lispro versus regular human insulin . Total glucose disposal was slightly greater with insulin glulisine than with regular human insulin , and was comparable to insulin lispro , although it decreased with increasing insulin resistance ( HOMA index ) with all insulins . Time to 20 % ( early glucose disposal ) and 80 % ( bulk of activity ) of total GIR-AUC were shorter for insulin glulisine and insulin lispro versus regular human insulin . This was corroborated by more rapid and shorter residing pharmacokinetic profiles of insulin glulisine and insulin lispro versus regular human insulin , evidence d by shorter times to 20 % of total INS-AUC , INS-C ( max ) ( INS-t ( max ) ) , and mean residence time . Moreover , time to 20 % of total GIR-AUC demonstrated a less rapid-acting profile for insulin lispro versus insulin glulisine , which was consistent with the slightly less rapid pharmacokinetic profile of insulin lispro . There was no significant correlation between BMI or subcutaneous fat thickness and pharmacokinetic or pharmacodynamic profiles for insulin glulisine , unlike insulin lispro and regular human insulin . CONCLUSIONS /INTERPRETATION Insulin glulisine and insulin lispro demonstrated substantially more rapid time-action profiles than regular human insulin in obese non-diabetic subjects , which prevailed with insulin glulisine irrespective of BMI and subcutaneous fat thickness Human insulin synthesis ed by recombinant DNA technology was compared with highly purified porcine insulin in healthy men . Intracutaneous injection over a wide range of concentrations of both insulins into five subjects gave rise to no local reactions over a 48 h period . The glycaemic response to st and ard subcutaneous injection at high and low dose levels was measured with both insulins in each of six men . Plasma glucose decrement with the two insulins was similar but human insulin was perhaps slightly more potent than porcine insulin at the low dose , and slightly less so at the high . The glycaemic response to the isulins , each infused intravenously at high and low concentrations for 1 h in a further six subjects , showed a similar trend . Depression of glycaemia with human insulin slightly exceeded that with porcine insulin at the low concentration infusion and fell slightly short of it at the high . Genetically synthesis ed human insulin seems to be safe and effective in man . Its dose-response relationship may differ from that of porcine insulin BACKGROUND The ability of short-acting insulin secretagogues to reduce the risk of diabetes or cardiovascular events in people with impaired glucose tolerance is unknown . METHODS In a double-blind , r and omized clinical trial , we assigned 9306 participants with impaired glucose tolerance and either cardiovascular disease or cardiovascular risk factors to receive nateglinide ( up to 60 mg three times daily ) or placebo , in a 2-by-2 factorial design with valsartan or placebo , in addition to participation in a lifestyle modification program . We followed the participants for a median of 5.0 years for incident diabetes ( and a median of 6.5 years for vital status ) . We evaluated the effect of nateglinide on the occurrence of three co primary outcomes : the development of diabetes ; a core cardiovascular outcome that was a composite of death from cardiovascular causes , nonfatal myocardial infa rct ion , nonfatal stroke , or hospitalization for heart failure ; and an extended cardiovascular outcome that was a composite of the individual components of the core composite cardiovascular outcome , hospitalization for unstable angina , or arterial revascularization . RESULTS After adjustment for multiple testing , nateglinide , as compared with placebo , did not significantly reduce the cumulative incidence of diabetes ( 36 % and 34 % , respectively ; hazard ratio , 1.07 ; 95 % confidence interval [ CI ] , 1.00 to 1.15 ; P=0.05 ) , the core composite cardiovascular outcome ( 7.9 % and 8.3 % , respectively ; hazard ratio , 0.94 , 95 % CI , 0.82 to 1.09 ; P=0.43 ) , or the extended composite cardiovascular outcome ( 14.2 % and 15.2 % , respectively ; hazard ratio , 0.93 , 95 % CI , 0.83 to 1.03 ; P=0.16 ) . Nateglinide did , however , increase the risk of hypoglycemia . CONCLUSIONS Among persons with impaired glucose tolerance and established cardiovascular disease or cardiovascular risk factors , assignment to nateglinide for 5 years did not reduce the incidence of diabetes or the co primary composite cardiovascular outcomes . ( Clinical Trials.gov number , NCT00097786 . Aims /hypothesisThe aim of this cohort study was to investigate the risk of malignant neoplasms and mortality in patients with diabetes treated either with human insulin or with one of three insulin analogues . Methods Data were provided by the largest German statutory health insurance fund ( time-frame : January 1998 to June 2005 inclusive ) , on patients without known malignant disease who had received first-time therapy for diabetes mellitus exclusively with human insulin , aspart , lispro or glargine . The primary outcome was the diagnosis of a malignant neoplasm . Data were analysed by multiple Cox regression models adjusting for potential confounders . Results A total of 127,031 patients were included , with a mean follow-up time of 1.63 ( median 1.41 , maximum 4.41 ) years . A positive association between cancer incidence and insulin dose was found for all insulin types . Because patients receiving combined therapy with insulin analogues and human insulin were excluded , the mean daily dose was much lower for glargine than for human insulin , and a slightly lower cancer incidence in the glargine group was found . After adjusting for dose , a dose-dependent increase in cancer risk was found for treatment with glargine compared with human insulin ( p < 0.0001 ) : the adjusted HR was 1.09 ( 95 % CI 1.00 to 1.19 ) for a daily dose of 10 IU , 1.19 ( 95 % CI 1.10 to 1.30 ) for a daily dose of 30 IU , and 1.31 ( 95 % CI 1.20 to 1.42 ) for a daily dose of 50 IU . No increased risk was found for aspart ( p = 0.30 ) or lispro ( p = 0.96 ) compared with human insulin . Conclusions /interpretationConsidering the overall relationship between insulin dose and cancer , and the lower dose with glargine , the cancer incidence with glargine was higher than expected compared with human insulin . Our results based on observational data support safety concerns surrounding the mitogenic properties of glargine in diabetic patients . Prospect i ve long-term studies are needed to further evaluate the safety of insulin analogues , especially glargine BACKGROUND Basal insulin therapy does not stop loss of β-cell function , which is the hallmark of type 2 diabetes mellitus , and thus diabetes control inevitably deteriorates . Insulin degludec is a new , ultra-longacting basal insulin . We aim ed to assess efficacy and safety of insulin degludec compared with insulin glargine in patients with type 2 diabetes mellitus . METHODS In this 52 week , phase 3 , open-label , treat-to-target , non-inferiority trial , undertaken at 123 sites in 12 countries , we enrolled adults ( aged ≥18 years ) with type 2 diabetes mellitus and a glycated haemoglobin ( HbA(1c ) ) of 7·0 - 10·0 % after 3 months or more of any insulin regimen ( with or without oral antidiabetic drugs ) . We r and omly allocated eligible participants in a 3:1 ratio to receive once-daily subcutaneous insulin degludec or glargine , stratified by previous insulin regimen , via a central interactive response system . Basal insulin was titrated to a target plasma glucose concentration of 3·9-<5·0 mmol/L self-measured before breakfast . The primary outcome was non-inferiority of degludec to glargine measured by change in HbA(1c ) from baseline to week 52 ( non-inferiority limit of 0·4 % ) by ANOVA in the full analysis set . We assessed rates of hypoglycaemia in all treated patients . This study is registered with Clinical Trials.gov , number NCT00972283 . FINDINGS 744 ( 99 % ) of 755 participants r and omly allocated degludec and 248 ( 99 % ) of 251 allocated glargine were included in the full analysis set ( mean age 58·9 years [ SD 9·3 ] , diabetes duration 13·5 years [ 7·3 ] , HbA(1c ) 8·3 % [ 0·8 ] , and fasting plasma glucose 9·2 mmol/L [ 3·1 ] ) ; 618 ( 82 % ) and 211 ( 84 % ) participants completed the trial . After 1 year , HbA(1c ) decreased by 1·1 % in the degludec group and 1·2 % in the glargine group ( estimated treatment difference [ degludec-glargine ] 0·08 % , 95 % CI -0·05 to 0·21 ) , confirming non-inferiority . Rates of overall confirmed hypoglycaemia ( plasma glucose < 3·1 mmol/L or severe episodes requiring assistance ) were lower with degludec than glargine ( 11·1 vs 13·6 episodes per patient-year of exposure ; estimated rate ratio 0·82 , 95 % CI 0·69 to 0·99 ; p=0·0359 ) , as were rates of nocturnal confirmed hypoglycaemia ( 1·4 vs 1·8 episodes per patient-year of exposure ; 0·75 , 0·58 to 0·99 ; p=0·0399 ) . Rates of severe hypoglycaemia seemed similar ( 0·06 vs 0·05 episodes per patient-year of exposure for degludec and glargine ) but were too low for assessment of differences . Rates of other adverse events did not differ between groups . INTERPRETATION A policy of suboptimum diabetes control to reduce the risk of hypoglycaemia and its consequences in advanced type 2 diabetes mellitus might be unwarranted with newer basal insulins such as degludec , which are associated with lower risks of hypoglycaemia than insulin glargine . FUNDING Novo Nordisk A comparison of the plasma glucose and insulin day profiles between two pr and ial rapid-acting insulin analogues , insulin glulisine ( glulisine ) and insulin lispro ( lispro ) , in 18 obese subjects with Type 2 diabetes . Subjects ( body mass index : males , 36.7 [ 33.2 - 43.8 ] kg/m(2 ) ; females , 40.0 [ 35.7 - 46.5 ] kg/m(2 ) ) received subcutaneous glulisine or lispro ( 0.15 U/kg ) at 4-h intervals immediately ( within 2 min ) before three st and ard test meals during each of two 12-h , r and omised , open-label , crossover studies ( 7+/-2-day interval between each ) . Overall , prepr and ial-subtracted glucose concentrations ( area under the curve ) were similar on the glulisine and lispro study days . However , the mean of the three maximal prepr and ial subtracted plasma glucose concentrations ( DeltaGLU(max ) ) were lower with glulisine versus lispro ( 12 % ; p<0.01 ) . Mean concentrations of insulin analogue were significantly higher post-meal with glulisine ( p<0.01 for all ) . Post hoc analysis showed a significantly faster absorption rate for glulisine versus lispro in the first 30 min post-meal ( estimated difference 0.48 microU/min ; p<0.0001 ) . Only two cases of hypoglycaemia were reported ; both from one subject during the lispro day . When glulisine is injected immediately before a meal in obese patients with Type 2 diabetes , glulisine achieves significantly lower glucose excursions over lispro . Significantly faster absorption with higher and sustained post-meal levels of insulin analogue was achieved at every meal with glulisine versus lispro |
13,878 | 28,489,568 | Subgroup analyses of age , cytogenetics risk , AML type and bone marrow blast percentage showed no significant differences of treatment response to decitabine .
In conclusion , decitabine is an effective and well-tolerated therapeutic alternative with acceptable side effects in elderly AML patients | Elderly patients with acute myeloid leukemia ( AML ) have limited treatment options concerned about their overall fitness and potential treatment related mortality .
Although a number of clinical trials demonstrated benefits of decitabine treatment in elderly AML patients , the results remains controversial .
A meta- analysis was performed to evaluate efficacy and safety of decitabine in treatment of elderly AML patients . | BACKGROUND In a multicenter , r and omized , open-label phase III study , patients ≥ 65 years with newly diagnosed AML received decitabine 20 mg/m(2 ) once daily for 5 days every 4 weeks ( n = 242 ) or treatment choice ( supportive care or cytarabine 20 mg/m(2 ) once daily for 10 days every 4 weeks ; n = 243 ) . Decitabine use demonstrated greater response rates ( P = .001 ) and OS data favored decitabine . PATIENTS AND METHODS In a post hoc sensitivity analysis of mature data of patients in the intent-to-treat population ( N = 485 ) , OS at 3 , 6 , 12 , 18 , and 24 months after r and omization was estimated for each arm using Kaplan-Meier methods . Age , cytogenetic risk , and Eastern Cooperative Oncology Group performance status were used as stratification factors in the Cox regression model to estimate the hazard ratio . RESULTS A survival advantage was seen with decitabine at each cutoff time point ; hazard ratios for OS for decitabine vs. treatment choice were 0.83 , 0.71 , 0.83 , 0.80 , and 0.79 at 3 , 6 , 12 , 18 , and 24 months , respectively . A trend toward improved OS with decitabine was observed at fixed time points over 2 years . CONCLUSION Decitabine should be considered as a treatment option for older patients with AML and poor prognostic risk factors Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Introduction . The incidence of Acute Myeloid Leukemia ( AML ) increases progressively with age and its treatment is challenging . This prospect i ve case control study was undertaken to compare the safety , efficacy , and cost-effectiveness of decitabine with those of cytarabine in older patients with newly diagnosed AML who are not fit for intensive chemotherapy . Material s and Methods . 30 eligible patients above 60 years old with newly diagnosed AML were assigned to receive decitabine or cytarabine . The primary end point was overall survival ( OS ) . The secondary objective was to compare adverse events and cost-effectiveness of therapy in the two study groups . Results . In this study , 15 patients received decitabine and 15 patients received cytarabine . The median OS was 5.5 months for each of the treatment groups . The hazard ratio between the treatment groups was 0.811 with 95 % CI of 0.390 to 1.687 . Toxicity profile was similar in both groups . Cost per cycle of chemotherapy in INR was 24,200 for decitabine and 1,600 for low-dose cytarabine group . Median of simplified cost-effectiveness ratio was 0.00022 for decitabine group and 0.0034 for low-dose cytarabine group . Conclusions . For elderly patients with AML , decitabine and low-dose cytarabine should be chosen based on the patient 's choice and affordability . Our study has shown that both of these agents have similar OS and toxicity . Low-dose cytarabine scores over decitabine in developing countries as it is more cost-effective We conducted an open-label phase 1 study exploring the feasibility , safety , and biologic activity of epigenetic priming with decitabine before st and ard induction chemotherapy in patients with less-than-favorable risk of acute myelogenous leukemia ( AML ) . We directly compared the clinical and DNA-hypomethylating activity of decitabine delivered at 20 mg/m² by either a 1-hour infusion ( Arm A ) or a continuous infusion ( Arm B ) for 3 , 5 , or 7 days before a single , st and ard induction with infusional cytarabine ( 100 mg/m² for 7 days ) and daunorubicin ( 60 mg/m² × 3 doses ) . Toxicity was similar to that of st and ard induction chemotherapy alone . Although we did not identify a maximum tolerated dose , there was more gastro-intestinal toxicity with 7 days of decitabine priming . Decitabine induced DNA hypomethylation at all dose levels and there was a trend toward greater hypomethylation in CD34(+ ) bone marrow cells when decitabine was delivered by a short pulse ( Arm A ) . Twenty-seven subjects ( 90 % ) responded to therapy : 17 with complete remission ( 57 % ) and 10 with partial remission ( 33 % ) . Of the patients with partial remission to protocol treatment , 8 achieved remission to their next therapy , bringing the overall complete remission rate to 83 % . We conclude that epigenetic priming of intensive chemotherapy can be safely delivered in an attempt to improve response rates . This trial was registered at www . clinical trials.gov as NCT00538876 Background The treatment of acute myeloid leukemia of older , medically non-fit patients still poses a highly unmet clinical need , and only few large , prospect i ve studies have been performed in this setting . Given the established activity of hypomethylating agents such as 5-aza-2'-deoxycytidine ( decitabine ) in myelodysplastic syndromes and acute myeloid leukemia with 20–30 % bone marrow blasts , we investigated whether this drug is also active in patients with more than 30 % blasts . Design and Methods To evaluate the efficacy and toxicity of decitabine in patients over 60 years old with untreated acute myeloid leukemia ineligible for induction chemotherapy , 227 patients ( median age , 72 years ) , many with comorbidities , adverse cytogenetics and /or preceding myelodysplastic syndrome were treated with this hypomethylating agent . During the initial decitabine treatment ( 135 mg/m2 total dose infused intravenously over 72 hours every 6 weeks ) , a median of two cycles was administered ( range , 1–4 ) . All-trans retinoic acid was administered to 100 patients during course 2 . Fifty-two patients who completed four cycles of treatment subsequently received a median of five maintenance courses ( range , 1–19 ) with a lower dose of decitabine ( 20 mg/m2 ) infused over 1 hour on 3 consecutive days every 4–6 weeks . Results The complete and partial remission rate was 26 % , 95 % CI ( 20 % , 32 % ) , and an antileukemic effect was noted in 26 % of patients . Response rates did not differ between patients with or without adverse cytogenetics ; patients with monosomal karyotypes also responded . The median overall survival from the start of decitabine treatment was 5.5 months ( range , 0–57.5 + ) and the 1-year survival rate was 28 % , 95%CI ( 22%,34 % ) . Toxicities were predominantly hematologic . Conclusions Decitabine is well tolerated by older , medically non-fit patients with acute myeloid leukemia ; myelosuppression is the major toxicity . The response rate and overall survival were not adversely influenced by poor-risk cytogenetics or myelodysplastic syndrome . Because of these encouraging results , r and omized studies evaluating single-agent decitabine versus conventional treatment are warranted . The study is registered with the German Clinical Trials Registry , number DRKS00000069 Decitabine may open the chromatin structure of leukemia cells making them accessible to the calicheamicin epitope of gemtuzumab ozogamicin ( GO ) . A total of 110 patients ( median age 70 years ; range 27–89 years ) were treated with decitabine and GO in a trial design ed on model-based futility to accommo date subject heterogeneity : group 1 : relapsed/refractory acute myeloid leukemia ( AML ) with complete remission duration ( CRD ) < 1 year ( N=28 , 25 % ) ; group 2 : relapsed/refractory AML with CRD ⩾1 year ( N=5 , 5 % ) ; group 3 : untreated AML unfit for intensive chemotherapy or untreated myelodysplastic syndrome ( MDS ) or untreated myelofibrosis ( MF ; N=57 , 52 % ) ; and group 4 : AML evolving from MDS or relapsed/refractory MDS or MF ( N=20 , 18 % ) . Treatment consisted of decitabine 20 mg/m2 daily for 5 days and GO 3 mg/m2 on day 5 . Post-induction therapy included five cycles of decitabine+GO followed by decitabine alone . Complete remission (CR)/CR with incomplete count recovery was achieved in 39 ( 35 % ) patients ; group 1= 5/28 ( 17 % ) , group 2=3/5 ( 60 % ) , group 3=24/57 ( 42 % ) and group 4=7/20 ( 35 % ) . The 8-week mortality in groups 3 and 4 was 16 % and 10 % , respectively . Common drug-related adverse events included nausea , mucositis and hemorrhage . Decitabine and GO improved the response rate but not overall survival compared with historical outcomes in untreated AML ⩾60 years BACKGROUND The molecular determinants of clinical responses to decitabine therapy in patients with acute myeloid leukemia ( AML ) or myelodysplastic syndromes ( MDS ) are unclear . METHODS We enrolled 84 adult patients with AML or MDS in a single-institution trial of decitabine to identify somatic mutations and their relationships to clinical responses . Decitabine was administered at a dose of 20 mg per square meter of body-surface area per day for 10 consecutive days in monthly cycles . We performed enhanced exome or gene-panel sequencing in 67 of these patients and serial sequencing at multiple time points to evaluate patterns of mutation clearance in 54 patients . An extension cohort included 32 additional patients who received decitabine in different protocol s. RESULTS Of the 116 patients , 53 ( 46 % ) had bone marrow blast clearance ( < 5 % blasts ) . Response rates were higher among patients with an unfavorable-risk cytogenetic profile than among patients with an intermediate-risk or favorable-risk cytogenetic profile ( 29 of 43 patients [ 67 % ] vs. 24 of 71 patients [ 34 % ] , P<0.001 ) and among patients with TP53 mutations than among patients with wild-type TP53 ( 21 of 21 [ 100 % ] vs. 32 of 78 [ 41 % ] , P<0.001 ) . Previous studies have consistently shown that patients with an unfavorable-risk cytogenetic profile and TP53 mutations who receive conventional chemotherapy have poor outcomes . However , in this study of 10-day courses of decitabine , neither of these risk factors was associated with a lower rate of overall survival than the rate of survival among study patients with intermediate-risk cytogenetic profiles . CONCLUSIONS Patients with AML and MDS who had cytogenetic abnormalities associated with unfavorable risk , TP53 mutations , or both had favorable clinical responses and robust ( but incomplete ) mutation clearance after receiving serial 10-day courses of decitabine . Although these responses were not durable , they result ed in rates of overall survival that were similar to those among patients with AML who had an intermediate-risk cytogenetic profile and who also received serial 10-day courses of decitabine . ( Funded by the National Cancer Institute and others ; Clinical Trials.gov number , NCT01687400 . ) Novel , non-intensive treatment options in older MDS/AML patients planned for allografting , with the goal of down-staging the underlying disease and bridging time to transplantation , are presently being developed . 5-azacytidine and decitabine ( DAC ) are of particular interest , as they can be given repetitively , with very limited non-hematologic toxicity and result in responses both in MDS and AML even at low doses . We describe 15 consecutive patients ( median age 69 years , range 60–75 years ) with MDS ( n=10 ) or AML ( n=5 ) who all received first-line treatment with DAC and subsequent allografting ( from sibling donor in four patients , unrelated donor in 11 ) after reduced-intensity conditioning with the FBM regimen . Successful engraftment was attained in 14/15 patients , all of whom achieved a CR , with a median duration of 5 months ( range 1 + to 51 + ) . Six of these 14 patients are alive ( 4 with complete donor chimerism ) , 8 have died either from relapse ( n=4 ) or treatment-related complications while in CR ( n=4 ) . We conclude that allografting after low-dose DAC and subsequent conditioning with FBM is feasible , with no unexpected toxicities and appears as a valid alternative to st and ard chemotherapy ( ‘ InDACtion instead of induction ’ ) in elderly patients with MDS/AML PURPOSE Older patients with acute myeloid leukemia ( AML ) have limited treatment options because of the lack of effectiveness and the toxicity of available therapies . We investigated the efficacy and toxicity of the hypomethylating agent decitabine as initial therapy in older patients with AML . PATIENTS AND METHODS In this multicenter , phase II study , patients older than 60 years who had AML ( ie , > 20 % bone marrow blasts ) and no prior therapy for AML were treated with decitabine 20 mg/m(2 ) intravenously for 5 consecutive days of a 4-week cycle . Response was assessed by weekly CBC and bone marrow biopsy after cycle 2 and after each subsequent cycle . Patients continued to receive decitabine until disease progression or an unacceptable adverse event occurred . RESULTS Fifty-five patients ( mean age , 74 years ) were enrolled and were treated with a median of three cycles ( range , one to 25 cycles ) of decitabine . The expert- review ed overall response rate was 25 % ( complete response rate , 24 % ) . The response rate was consistent across subgroups , including in patients with poor-risk cytogenetics and in those with a history of myelodysplastic syndrome . The overall median survival was 7.7 months , and the 30-day mortality rate was 7 % . The most common toxicities were myelosuppression , febrile neutropenia , and fatigue . CONCLUSION Decitabine given in a low-dose , 5-day regimen has activity as upfront therapy in older patients with AML , and it has acceptable toxicity and 30-day mortality Older patients with acute myeloid leukemia ( AML ) have poor outcomes with st and ard induction chemotherapy . We retrospectively review ed our institute 's experience with epigenetic ( Epi ) versus cytarabine‐ and anthracycline‐based intensive chemotherapy ( IC ) as induction in newly diagnosed AML patients aged 60 years and older . One hundred sixty‐seven patients ( n = 84 , IC ; n = 83 , Epi ) were assessed ; 69 patients received decitabine and 14 azacitidine . Baseline characteristics between the IC and Epi patient cohorts were not statistically different except for age , initial white blood cell count , and comorbidity index . Overall response rate ( ORR , 50 % vs. 28 % , respectively , P < 0.01 ) and complete response rate ( CRR , 43 % vs. 20 % , respectively , P < 0.01 ) were superior following IC vs. Epi . Although univariate analysis demonstrated longer overall survival after IC ( 10.7 vs. 9.1 months , P = 0.012 ) , multivariate analysis showed no independent impact of induction treatment . Treatment‐related mortality was not statistically different in the two groups . Outcomes of patients with secondary , poor cytogenetic risk , FLT‐3 mutated AML , or relapsed/refractory disease after IC or Epi were not significantly different . Outcomes of patients receiving IC versus a 10‐day decitabine regimen ( n = 63 ) also were not significantly different . Our results suggest that IC and Epi therapy are clinical ly equivalent approaches for upfront treatment of older patients with AML and that other factors ( feasibility , toxicity , cost , etc . ) should drive treatment decisions . Prospect i ve r and omized trials to determine the optimal induction approach for specific patient subsets are needed . Am . J. Hematol . 90:639–646 , 2015 . © 2015 Wiley Periodicals , 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 A phase II clinical trial with single-agent decitabine was conducted in older patients ( ≥60 years ) with previously untreated acute myeloid leukemia ( AML ) who were not c and i date s for or who refused intensive chemotherapy . Subjects received low-dose decitabine at 20 mg/m2 i.v . over 1 h on days 1 to 10 . Fifty-three subjects enrolled with a median age of 74 years ( range , 60–85 ) . Nineteen ( 36 % ) had antecedent hematologic disorder or therapy-related AML ; 16 had complex karyotypes ( ≥3 abnormalities ) . The complete remission rate was 47 % ( n = 25 ) , achieved after a median of three cycles of therapy . Nine additional subjects had no morphologic evidence of disease with incomplete count recovery , for an overall response rate of 64 % ( n = 34 ) . Complete remission was achieved in 52 % of subjects presenting with normal karyotype and in 50 % of those with complex karyotypes . Median overall and disease-free survival duration s were 55 and 46 weeks , respectively . Death within 30 days of initiation of treatment occurred in one subject ( 2 % ) , death within 8 weeks in 15 % of subjects . Given the DNA hypomethylating effect of decitabine , we examined the relationship of clinical response and pretreatment level of miR-29b , previously shown to target DNA methyltransferases . Higher levels of miR-29b were associated with clinical response ( P = 0.02 ) . In conclusion , this schedule of decitabine was highly active and well tolerated in this poor-risk cohort of older AML patients . Levels of miR-29b should be vali date d as a predictive factor for stratification of older AML patients to decitabine treatment PURPOSE To determine an optimal biologic dose ( OBD ) of decitabine as a single agent and then the maximum-tolerated dose ( MTD ) of valproic acid ( VA ) combined with decitabine in acute myeloid leukemia ( AML ) . PATIENTS AND METHODS Twenty-five patients ( median age , 70 years ) were enrolled ; 12 were untreated and 13 had relapsed AML . To determine an OBD ( based on a gene re-expression end point ) , 14 patients received decitabine alone for 10 days . To determine the MTD , 11 patients received decitabine ( at OBD , days 1 through 10 ) plus dose-escalating VA ( days 5 through 21 ) . RESULTS The OBD of decitabine was 20 mg/m(2)/d intravenously , with limited nonhematologic toxicity . In patients treated with decitabine plus VA , dose-limiting encephalopathy occurred in two of two patients at VA 25 mg/kg/d and one of six patients at VA 20 mg/kg/d . Drug-induced re-expression of estrogen receptor ( ER ) was associated with clinical response ( P < or = .05 ) . ER promoter demethylation , global DNA hypomethylation , depletion of DNA methyltransferase enzyme , and histone hyperacetylation were also observed . In an intent-to-treat analysis , the response rate was 44 % ( 11 of 25 ) . Of 21 assessable patients , 11 ( 52 % ) responded : four with morphologic and cytogenetic complete remission ( CR ; each had complex karyotype ) , four with incomplete CR , and three with partial remission . In untreated AML , four of nine assessable patients achieved CR . Clinical responses appeared similar for decitabine alone or with VA . CONCLUSION Low-dose decitabine was safe and showed encouraging clinical and biologic activity in AML , but the addition of VA led to encephalopathy at relatively low doses . On the basis of these results , additional studies of decitabine ( 20 mg/m(2)/d for 10 days ) alone or with an alternative deacetylating agent are warranted The treatment of older adults with acute myeloid leukemia ( AML ) using st and ard intensive chemotherapy has been associated with poor outcomes . Effective , less toxic therapies are needed to achieve and maintain durable remissions We recently reported promising clinical activity for a 10-day regimen of decitabine in older AML patients ; high miR-29b expression associated with clinical response . Subsequent pre clinical studies with bortezomib in AML cells have shown drug-induced miR-29b up-regulation , result ing in loss of transcriptional activation for several genes relevant to myeloid leukemogenesis , including DNA methyltransferases and receptor tyrosine kinases . Thus , a phase 1 trial of bortezomib and decitabine was developed . Nineteen poor-risk AML patients ( median age 70 years ; range , 32 - 84 years ) enrolled . Induction with decitabine ( 20 mg/m(2 ) intravenously on days 1 - 10 ) plus bortezomib ( escalated up to the target 1.3 mg/m(2 ) on days 5 , 8 , 12 , and 15 ) was tolerable , but bortezomib-related neuropathy developed after repetitive cycles . Of previously untreated patients ( age ≥ 65 years ) , 5 of 10 had CR ( complete remission , n = 4 ) or incomplete CR ( CRi , n = 1 ) ; 7 of 19 overall had CR/CRi . Pharmacodynamic analysis showed FLT3 down-regulation on day 26 of cycle 1 ( P = .02 ) . Additional mechanistic studies showed that FLT3 down-regulation was due to bortezomib-induced miR-29b up-regulation ; this led to SP1 down-regulation and destruction of the SP1/NF-κB complex that transactivated FLT3 . This study demonstrates the feasibility and preliminary clinical activity of decitabine plus bortezomib in AML and identifies FLT3 as a novel pharmacodynamic end point for future trials |
13,879 | 27,203,412 | Although some articles in the literature are in favor of the use of a postoperative brace after anterior cruciate ligament ( ACL ) reconstruction , this review found that several systematic review s and other reports on the topic do not support the use of a postoperative brace after ACL reconstruction .
There is no scientific evidence so far to support the routine use of a functional knee brace following a successful ACL reconstruction in the postoperative course .
Most authors believe that bracing is not necessary .
Postoperative bracing after ACL reconstruction does not seem to help with pain , function , rehabilitation , and stability . | null | null |
13,880 | 24,122,775 | Conclusion It is likely that PA is a sustainable outcome from interventions in children and adolescents , and there is reasonable evidence that interventions of longer than 1 year and interventions that utilize a theoretical model or framework are effective in producing this sustained impact . | Background There is emerging evidence for positive associations between physical activity ( PA ) , fitness , and fundamental movement skill ( FMS ) competence , for both children and adolescents .
Current review s of interventions to improve these variables note few studies conduct follow-up assessment s to assess behavior maintenance .
Objective The aim of this systematic review was to determine whether typically developing children and adolescents ( aged 3–18 years ) who have participated in school-based interventions have sustained outcomes in PA , fitness , and /or FMS . | OBJECTIVE The objective of this study was to test whether heart-rate feedback prompts increased physical activity ( PA ) in primary school students . METHODS A controlled trial with 210 9 - 11 year olds from subsidized Hong Kong Government primary schools was completed in December 2006 . Schools were r and omly assigned to one of three groups : Control ( CG ) ; Educational program ( EG ) ; No-educational program ( NEG ) . INTERVENTION In a short-term school-based intervention , heart-rate feedback was given either in combination with an educational program ( EG ) or in isolation ( NEG ) . Long-term retention was assessed in comparison to the control group after 6 months follow-up . MAIN OUTCOME MEASURES Physical activity and changes in attraction to PA . RESULTS In the short-term , heart-rate monitor feedback increased total daily PA by an average of 24 % ( p<0.001 ) and vigorous PA by 0.6 % ( p<0.05 ) . No change was found for moderate PA . Increases occurred regardless of involvement in the educational program , and in the absence of any change in attitudes towards PA . No long-term retention was apparent . CONCLUSIONS The findings from the study suggest that feedback from heart-rate monitors encourages low intensity PA , but when removed increases do not persist Developing an evidence base for making public health decisions will require using data from evaluation studies with r and omized and nonr and omized design s. Assessing individual studies and using studies in quantitative research syntheses require transparent reporting of the study , with sufficient detail and clarity to readily see differences and similarities among studies in the same area . The Consoli date d St and ards of Reporting Trials ( CONSORT ) statement provides guidelines for transparent reporting of r and omized clinical trials . We present the initial version of the Transparent Reporting of Evaluations with Nonr and omized Design s ( TREND ) statement . These guidelines emphasize the reporting of theories used and descriptions of intervention and comparison conditions , research design , and methods of adjusting for possible biases in evaluation studies that use nonr and omized design The purpose of this study was to investigate the associations between obesity and motor coordination ability in Taiwanese children with and without developmental coordination disorder ( DCD ) . 2029 children ( 1078 boys , 951 girls ) aged nine to ten years were chosen r and omly from 14 elementary schools across Taiwan . We used bioelectrical impedance analysis to measure percentage of body fat ( PBF ) and the Movement Assessment Battery for Children test ( MABC test ) to evaluate the motor coordination ability . Using cut-off points based on PBF from past studies , boys and girls were divided into obese , overweight and normal-weight groups , respectively . In boys , total impairment scores and scores on balance subtest in the MABC were significantly higher in the obese and overweight groups when compared against the normal-weight group . Girls in the obese and the overweight groups had higher balance impairment scores than those of the normal-weight group . Among boys , the prevalence of obesity was highest in the DCD group , when compared to the borderline DCD and TD boys . A higher percentage of DCD girls were overweight and obese than TD girls . Obesity may be associated with poor motor coordination ability among boys and girls , and particularly in relation to balance ability . Children with DCD may have a higher risk to be overweight or obese in Taiwan OBJECTIVE To assess differences through grade 8 in diet , physical activity , and related health indicators of students who participated in the Child and Adolescent Trial for Cardiovascular Health ( CATCH ) school and family intervention from grade s 3 through 5 . DESIGN Follow-up of the 4-center , r and omized , controlled field trial with 56 intervention and 40 control elementary schools . PARTICIPANTS We studied 3714 ( 73 % ) of the initial CATCH cohort of 5106 students from ethnically diverse background s in California , Louisiana , Minnesota , and Texas at grade s 6 , 7 , and 8 . RESULTS Self-reported daily energy intake from fat at baseline was virtually identical in the control ( 32.7 % ) and intervention ( 32.6 % ) groups . At grade 5 , the intake for controls remained at 32.2 % , while the intake for the intervention group declined to 30.3 % ( P<.001 ) . At grade 8 , the between-group differential was maintained ( 31.6 % vs 30.6 % , P = .01 ) . Intervention students maintained significantly higher self-reported daily vigorous activity than control students ( P = .001 ) , although the difference declined from 13.6 minutes in grade 5 to 11.2 , 10.8 , and 8.8 minutes in grade s 6 , 7 , and 8 , respectively . Significant differences in favor of the intervention students also persisted at grade 8 for dietary knowledge and dietary intentions , but not for social support for physical activity . No impact on smoking behavior or stages of contemplating smoking was detected at grade 8 . No significant differences were noted among physiologic indicators of body mass index , blood pressure , or serum lipid and cholesterol levels . CONCLUSION The original CATCH results demonstrated that school-level interventions could modify school lunch and school physical education programs as well as influence student behaviors . This 3-year follow-up without further intervention suggests that the behavioral changes initiated during the elementary school years persisted to early adolescence for self-reported dietary and physical activity behaviors Background Physical inactivity is recognised as a public health concern within children and interventions to increase physical activity are needed . GreatFun2Run was a school-based healthy lifestyles intervention that showed positive changes in physical activity levels and body composition immediately post-intervention . The purpose of this paper was to examine whether these changes in physical activity and body composition were maintained 18 - 20 months after the intervention ended . Method Participants ( n = 589 , aged 7 - 11 yrs ) from 4 intervention and 4 control schools took part in the 10-month intervention , of which 421 ( 71 % ) were present for follow-up . The intervention comprised a CD-rom learning and teaching re source for teachers ; an interactive website for pupils , teachers and parents ; two highlight physical activity events ( 1 mile school runs/walks ) ; a local media campaign ; and a summer activity wall planner and record . R and omisation was not possible because of local media content . Outcome measures were objective ly measured physical activity ( pedometers and accelerometers ) and body composition variables ( body mass index , waist circumference , estimated percent body fat , and sum of skinfolds ) . Teacher interviews and participant focus groups were conducted . Multi-level modelling was employed for the data analysis . Results Both control and intervention participants had increased their physical activity at follow-up but there was no group by time interaction ( control : 2726 steps per day increase ; intervention 3404 steps per day increase , p > .05 ) . There were significant increases in estimated percent body fat , sum of skinfolds , waist circumference and body mass index ( BMI ) with increasing age . In the control group , there was evidence for a plateauing in the rate of change in all body composition variables with increasing age , except BMI . In contrast , significant interaction terms suggest that the rate of change in waist circumference , BMI and BMI SDS continued to increase with age in the intervention group . Teacher interviews suggested that because of time pressures , competing re sources , curriculum dem and s and staff changes the majority of teachers had not continued to use the re sources . Conclusions While the intervention initially produced positive changes in physical activity levels and body composition , these changes were not sustained once the intervention ended . Facilitating long-term health behaviour change in children remains a challenge 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 Physical activity ( PA ) rates decline precipitously during the high school years and are consistently lower among adolescent girls than adolescent boys . Due to cultural barriers , this problem might be exacerbated in female Iranian adolescents . However , little intervention research has been conducted to try to increase PA participation rates with this population . Because PA interventions in schools have the potential to reach many children and adolescents , this study reports on PA intervention research conducted in all-female Iranian high schools . Methods A r and omized controlled trial was conducted to examine the effects of two six-month tailored interventions on potential determinants of PA and PA behavior . Students ( N = 161 ) were r and omly allocated to one of three conditions : an intervention based on Pender 's Health Promotion model ( HP ) , an intervention based on an integration of the health promotion model and selected constructs from the Transtheoretical model ( THP ) , and a control group ( CON ) . Measures were administered prior to the intervention , at post-intervention and at a six-month follow-up . Results Repeated measure ANOVAs showed a significant interaction between group and time for perceived benefits , self efficacy , interpersonal norms , social support , behavioral processes , and PA behavior , indicating that both intervention groups significantly improved across the 24-week intervention , whereas the control group did not . Participants in the THP group showed greater use of counter conditioning and stimulus control at post-intervention and at follow-up . While there were no significant differences in PA between the HP and CON groups at follow-up , a significant difference was still found between the THP and the CON group . Conclusion This study provides the first evidence of the effectiveness of a PA intervention based on Pender 's HP model combined with selected aspects of the TTM on potential determinants to increase PA among Iranian high school girls Aims : In this paper we evaluate the sustainability of changes of involvement in physical activity . The paper examines the effectiveness of a model aim ing at influencing the frequency of leisuretime physical activity , physical fitness and body constituency in youth . Methods : The baseline of this study was a r and omly selected sample of 13 year olds who participated in an intervention programme carried out in three schools in Poznan in 2005—08 . From a total of 199 adolescent boys a sub sample of 38 individuals from the experimental group and 34 from the control group were followed for 15 months after the interventional programme finished . From 170 girls , a sub sample of 33 from the experimental group and 32 girls from the control group were also r and omly selected for the follow-up study . Among the variables monitored were : physical fitness , body constituency , and frequency of leisuretime physical activity . All the variables were monitored in pre-test , post-test and follow-up examinations . Results : It was established that 15 months after the end of the interventional programme boys and girls from the intervention groups maintained a higher level of leisuretime physical activity than their control group peers , and similarly in the case of selected health-related components of physical fitness . No distinctive differences were found in the case of body constituency , though , apart from muscle mass and the sum of skinfolds in girls . Conclusions : The study exposed an increase in leisuretime physical activity in time and a positive influence on selected components of health-related variables . The findings confirm the effectiveness of a multi-level intervention programme involving self-determined out-of-school physical activity planning for school-age youths , indicating the importance of personal and social context Objectives : To evaluate the effectiveness of an intervention to prevent excess weight gain , reduce time spent in screen behaviours , promote participation in and enjoyment of physical activity ( PA ) , and improve fundamental movement skills among children . Participants : In 2002 , 311 children ( 78 % response ; 49 % boys ) , average age 10 years 8 months , were recruited from three government schools in low socioeconomic areas of Melbourne , Australia . Design : Group-r and omized controlled trial . Children were r and omized by class to one of the four conditions : a behavioural modification group ( BM ; n=66 ) ; a fundamental movement skills group ( FMS ; n=74 ) ; a combined BM/FMS group ( BM/FMS ; n=93 ) ; and a control ( usual curriculum ) group ( n=62 ) . Data were collected at baseline , post intervention , 6- and 12-month follow-up periods . Results : BMI data were available for 295 children at baseline and 268 at 12-month follow-up . After adjusting for food intake and PA , there was a significant intervention effect from baseline to post intervention on age- and sex-adjusted BMI in the BM/FMS group compared with controls ( −1.88 kg m−2 , P<0.01 ) , which was maintained at 6- and 12-month follow-up periods ( −1.53 kg m−2 , P<0.05 ) . Children in the BM/FMS group were less likely than controls to be overweight/obese between baseline and post intervention ( adjusted odds ratio (AOR)=0.36 , P<0.05 ) ; also maintained at 12-month follow-up ( AOR=0.38 , P<0.05 ) . Compared with controls , FMS group children recorded higher levels and greater enjoyment of PA ; and BM children recorded higher levels of PA and TV viewing across all four time points . Gender moderated the intervention effects for participation in and enjoyment of PA , and fundamental movement skills . Conclusion : This programme represents a promising approach to preventing excess weight gain and promoting participation in and enjoyment of PA . Examination of the mediators of this intervention and further tailoring of the programme to suit both genders is required UNLABELLED The aim of this study was to examine the relationship between motor proficiency and pedometer-determined physical activity in 5 - 6 year-old children . Participants ( n = 232 ) were r and omly recruited and assessed from 30 kindergartens in Northern Greece . Two trained research ers administered the measurements for the assessment of children 's motor proficiency by using the BOTMP-SF . Physical activity was assessed by OMRON pedometers . Significant relationships between BOTMP-SF st and ard score and steps ( S ) , aerobic walking time ( AWT ) and aerobic steps ( AS ) , ( p < .05 ) were found . When motor proficiency was divided into quartiles to assess the distribution of the relationship between motor proficiency and pedometer-derived variables , significant associations were found for AWT , S and AS ( p < .001 ) . Young children with high levels of motor proficiency were more active in contrast to their peers with lower motor proficiency . The findings add to the growing body of literature that considers motor skills/abilities as important elements of physical activity participation . ( ABBREVIATIONS S-steps per day ; AS-aerobic steps per day ; AWT-aerobic walking time ( minutes·day(-1 ) ) ; BOTMP-SF-Bruininks-Oseretsky Test of Motor Proficiency-Short Form ( st and ard score ) ) A major aim of the current study was to determine what classroom teachers perceived to be the greatest barriers affecting their capacity to deliver successful physical education ( PE ) programs . An additional aim was to examine the impact of these barriers on the type and quality of PE programs delivered . This study applied a mixed-mode design involving data source triangulation using semistructured interviews with classroom teachers ( n = 31 ) and teacher-completed question naires ( n = 189 ) from a r and om sample of 38 schools . Results identified the key factors inhibiting PE teachers , which were categorized as teacher-related or institutional . Interestingly , the five greatest barriers were defined as institutional or out of the teacher 's control . The major adverse effects of these barriers were evident in reduced time spent teaching PE and delivering PE lessons of question able quality |
13,881 | 22,914,481 | Complications were mostly related to catheter tube malfunction with no visceral injuries reported .
No differences in the rate of recatheterization or hospital stay were demonstrated .
: Based on the best available evidence , no route for bladder drainage in gynecologic patients is clearly superior .
The reduced rate of infective morbidity with suprapubic catheterization is offset by a higher rate of catheter-related complications and crucially does not translate into reduced hospital stay .
Minimally invasive surgery may alter the requirement for prolonged postoperative catheterization | OBJECTIVE : Suprapubic catheterization is commonly used for postoperative bladder drainage after gynecologic procedures .
However , recent studies have suggested an increased rate of complications compared with urethral catheterization . | Postoperative acute urinary retention was evaluated in the patients who underwent Pereyra procedure . Comparison of suprapubic and urethral catheterization . Between January 1994 and July 1995 , fifty two patients with urinary stress incontinence underwent Pereyra procedure , 31 female patient with suprapubic drainage ( cistofix Ch 15 ) and 17 urethral catherization with a latex foley catheter . Sponatneous micturition and urinary retention was evaluated until the catheter was removed . Mean age was 43.8 years ( 32 a 66 ) , the duration of suprapubic vesical drainage with suprapubic catheter were 3 days in 58.6 % of the patients , and more than 3 days in 41.29 % . Recatheterizacion in the patients with urethral drainage was more frequent . Urinary retention after 7 days was present in 23.99 % with suprapubic vesical drainage and 28.5 % with urethral catheter . Recatheterization is more frequent in patients with urethral catheter In a prospect i ve study the results of postoperative urinary discharge by suprapubic catheterisation ( SC ) are compared with those of transurethral catheterisation ( TC ) in a r and omised collective of gynaecological patients after vaginal hysterectomy with front ( resp . front and back ) plastic . During November 1979 and September 1980 157 patients were examined , 88 patients by suprapubic catheterisation and 69 by transurethral catheterisation , with r and om distribution . Additionally , 430 other patients with suprapubic aspiration after vaginal hysterectomy with front and /or back plastic performed between September 1980 and October 1982 were examined retrospectively especially under the aspect of possible complications . The advantages of suprapubic urinary discharge are shown in the significantly reduced rate of primary infections . 20.5 per cent of infections are opposed to 67.1 per cent in the comparative group with TC . Spontaneous miction was possible in the SC group two days earlier than in the group of TC ( 5.2 days opposed to 7.35 days ) . Additional drug treatment for restitution of the bladder function was more often necessary for patients with TC , although the results with 43.5 per cent against 29.5 per cent in the SC collective are not significant . The number of renewed catheterisations after removal of the catheter was higher by 27 per cent in the group of patients with SC . Subjective complaints were stated by patients with TC in 66.7 per cent against 18.2 per cent of women with SC . This result is significant . In the TC collective there were significantly more patients with leucocyturia ( 88.5 per cent against 48.7 per cent ) . Antibiotic treatment of an urinary tract infection with typical symptoms was necessary in 35.8 per cent for patients with TC and in 14.1 per cent for women with SC . ( ABSTRACT TRUNCATED AT 250 WORDS The objective of this study is to assess the impact of bladder catheterization on the incidence of postoperative urinary tract infection ( UTI ) and urinary retention ( PUR ) following laparoscopic-assisted vaginal hysterectomy ( LAVH ) . One hundred fifty patients undergoing LAVH were r and omly assigned to no catheter use , 1-day , and 2-day catheter groups . The relationship between preoperative , intraoperative , and postoperative factors and the rates of UTI and PUR were determined . The incidences of UTI and PUR were 9.3 % and 18.7 % , respectively . The highest rate of UTI occurred in the 2-day catheter group ; the highest rate of PUR occurred in no-catheter-use group . Multivariable logistical regression showed the duration of catheterization was the single predictor of UTI ; duration of catheterization and diabetes mellitus were predictors for PUR . While short-term indwelling catheterization result ed in decreased rate of PUR , UTI rate increased among patients undergoing LAVH . Nonetheless , most patients resumed normal urination shortly after surgery Abstract . Ninety‐two patients with preoperative sterile urine undergoing colposuspension or vaginal repair operation for stress urinary incontinence and /or genital descensus were r and omized to either suprapubic or transurethral postoperative catheter drainage . The prevalence of significant bac‐teriuria on the fifth postoperative day was statistically significantly lower when using suprapubic catheter ( 20.8 % ) than with transurethral catheter drainage ( 45.5 % ) . This applied especially to colposuspension . The rate of postoperatively impaired bladder emptying also tended to be reduced when using suprapubic catheter . At follow‐up after one year , postoperative bacteriuria was closely correlated to increased rates of both clinical cystitis and asymptomatic significant bacteriuria . Thus it is recommended to use suprapubic bladder drainage not only after colposuspension but also after vaginal repair in an effort to avoid an increased risk of urinary infections Introduction and hypothesisDifferent forms of urinary drainage are applied after anterior colporrhaphy . Suprapubic urinary catheter ( SUC ) and indwelling urinary catheter ( IUC ) for 2 to 96 h are preferred . If there is no difference in symptomatic urinary tract infection ( SUTI ) or complications between IUCs for 96 and 24 h , the latter will be considered sufficient . If IUCs have no higher rate of infections or complications compared to SUC for 96 h , the former could be considered sufficient . Methods It was a three-arm prospect i ve , r and omized study including 257 patients . The three arms were : IUCs for 24 h , IUCs for 96 h , and SUCs for 96 h. Results We found no significant difference in SUTIs between all three groups . Although the SUC arm showed no SUTIs , a significant higher rate of complications was seen . Conclusion The optimal bladder catheter after anterior colporrhaphy was , in our trial , the IUC for 24 A controversy exists concerning the most appropriate method of bladder drainage after vaginal hysterectomy and anterior-posterior repair . The present study compares the use of the Foley catheter and the suprapubic tube following these operations . One hundred and fifty suitable c and i date s were selected , with 75 using each system . The results showed that the suprapubic group had one-third the rate { 12 % vs 38 % ) of significant bacteriuria when compared to the Foley group at the time the instruments were removed on the fourth postoperative day . In addition the Foley group also had a significant increase in the number of positive urine cultures 6 weeks after the operation ( 10 % vs 2 % ) , a higher incidence of prolonged hospitalization ( greater than 6 days ) , and a more frequent use of bladder analgesics ( 69 % vs 41 % ) . Other advantages in the use of suprapubic tubes after vaginal surgery appeared to be ease of care by ward personnel , greater patient comfort , and a reduced incidence of severe complications . An additional finding of this study was related to the increase of significant bacteriuria in patients receiving cold knife conization prior to hysterectomy . This factor appeared to be constant regardless of the drainage system used although a greater number of cases were found in the Foley group OBJECTIVE To determine the potential benefits of ISC ( intermittent self-catheterisation ) over SPC ( supra-pubic catheterisation ) in the post-operative bladder care of women following radical hysterectomy . METHODS A prospect i ve r and omised controlled trial of women treated by radical hysterectomy for early stage cervical cancer . RESULTS . : 40 women were recruited to the study , 21 to ISC and 19 to SPC . All patients r and omised to ISC were able to learn the technique of ISC satisfactorily following a period of pre-operative training . The day 3 and day 5 positive CSU ( catheter specimen of urine ) rate was significantly higher in the ISC group ( 42 % and 63 % ) compared to the SPC group ( 6 % and 18 % ) , P = 0.05 and P = 0.004 , respectively ) . Eight of 17 patients r and omised to SPC ( 47 % ) documented having symptoms/problems arising from the SPC site of which 4 ( 23 % ) were shown to have a positive wound swab . There was no significant difference in length of period for bladder care between the two groups , P = 0.83 . However , there were significant differences in patient acceptability ( P = 0.009 ) , freedom to lead a normal life ( P = 0.000 ) , disturbance at night ( P = 0.006 ) and patient anxiety/embarrassment ( P = 0.005 ) between the two groups . CONCLUSIONS Patients are able to learn the technique of ISC without difficulty . Despite a greater urinary tract infection rate , the high incidence of SPC site problems can be avoided by use of ISC . The technique of ISC was seen to be more acceptable to patients allowing fewer disturbances at night , greater freedom to lead a normal life during the day and less anxiety/embarrassment compared to SPC In a prospect i ve r and omized study comprising 90 women undergoing vaginal plastic surgery , suprapubic and transurethral catheter drainage of the bladder were compared regarding urinary tract infection and asymptomatic bacteriuria . No statistically significant differences were found . The mean duration of catheterization was 4.9 days for suprapubic vs 3.3 days for transurethral catheter patients . Postoperative urinary tract infection was diagnosed in 23.7 % of patients with suprapubic and in 27.5 % of patients with transurethral catheters . Asymptomatic bacteriuria at catheter removal was found in 21.0 % of suprapubic and in 12.5 % of transurethral catheter patients . More mechanical complications were seen with SPCsthan with TUCs . It is concluded that the two methods involve similar risks of infectious complications but that SPCs have a higher rate of mechanical complications OBJECTIVE To compare the use of intermittent urethral catheterization with indwelling suprapubic catheterization in women undergoing surgery for urodynamic stress incontinence or uterovaginal prolapse . DESIGN R and omized controlled trial . SETTING Tertiary referral urogynaecology unit . POPULATION Women undergoing surgery for pelvic organ prolapse and /or stress urinary incontinence . METHODS Women were r and omized into one of two groups . Group 1 had bladder drainage using a suprapubic catheter inserted in theatre . The catheter was left on free drainage for 48 hours post-operatively before clamping . Group 2 was catheterized intermittently post-operatively . MAIN OUTCOME MEASURES Length of post-operative hospital stay : time to resume normal voiding ( defined as voided volumes greater than 200 mls and residual urine volumes less than 100 mls on three occasions ) ; number of urinary tract infections ( UTIs ) ; catheterization costs ; patient experience ( determined from question naire ) ; and a pain score . RESULTS 75 women were r and omized ; 38 to suprapubic catheterization ; 37 to intermittent catheterization . Three were withdrawn from study , leaving 36 women in each group . Groups were closely matched for age and type of surgery undertaken . Length of hospital stay and total duration of catheterization were both significantly shorter for the intermittent catheterization group ; although there was no difference in the rate of UTI between the two groups . There was no clear patient preference for a specific catheterization method . CONCLUSIONS The use of intermittent catheterization following urogynaecological surgery is associated with a more rapid return to normal micturition and a shorter hospital stay , although the clinical significance of the difference is perhaps limited Fifty-one patients with clinical and urodynamic diagnoses of stress urinary incontinence were r and omly allocated to either suprapubic ( N = 24 ) or transurethral ( N = 27 ) bladder drainage after vaginal surgery for stress incontinence ( revised Pereyra procedure ) . Postoperative use of suprapubic bladder drainage significantly reduced febrile morbidity ( calculated as fever index ; P < .01 ) and length of hospitalization ( P < .05 ) . Postoperative normal bladder functions resumed more quickly when suprapubic drainage was used ( P < .05 ) , so that most patients did not need bladder catheterization upon discharge , as opposed to more than half of those with Foley catheters , who left the hospital with a catheter in place ( P < .05 ) . We conclude that it is both beneficial and cost-effective to use suprapubic bladder drainage after a Pereyra operation for stress urinary incontinence STUDY OBJECTIVE We sought to evaluate the incidence of postoperative voiding dysfunction in patients undergoing vaginal hysterectomy ( VH ) or total laparoscopic hysterectomy ( TLH ) and to identify risk factors for the development of postoperative urinary retention after uncomplicated total hysterectomy . DESIGN Prospect i ve cohort study ( Canadian Task Force classification II-2 ) . SETTING Gynecology department of a university hospital . PATIENTS Two hundred thirty-three consecutive women undergoing TLH or VH for benign gynecologic disease . INTERVENTIONS A regimen of immediate catheter removal after the operation was instituted . A strict voiding trial protocol was used during the study period . Postoperative voiding dysfunction was defined as failure of first voiding trial after surgery ( urinary retention ) or postvoid residual volume of greater than 150 mL necessitating recatheterization . MEASUREMENTS AND MAIN RESULTS A total of 49 women ( 21 % ) developed postoperative voiding dysfunction , of which 32 ( 13.7 % ) had complete urinary retention and 17 ( 7.3 % ) had a postvoid residual volume greater than 150 mL. None of these patients experienced voiding dysfunction beyond 48 hours . There was no statistical correlation between development of postoperative voiding dysfunction and demographic , historic , preoperative , and postoperative variables collected . The only factor with significant impact on postoperative voiding dysfunction was vaginal approach to hysterectomy ( OR 2.8 ; 95 % CI 1.5 - 5.4 ) . Hospital stay was significantly longer for women experiencing voiding difficulties than for those who voided efficiently ( 2.2 + /- 0.8 [ 95 % CI 1.5 - 1.9 ] vs 1.7 + /- 1.2 [ 95 % CI 1.9 - 2.4 ] days ; p < .0001 ) . Voiding dysfunction was an independent predictor of postoperative urinary tract infection ( OR 4.9 ; 95 % CI 1.6 - 15.4 ) . CONCLUSION Patients undergoing VH are more likely to develop postoperative voiding dysfunction than those who undergo TLH , when a policy of immediate catheter removal after surgery is used Aim : To compare the effect of suprapubic and transurethral catheterization on postvoid residual volumes ( PRVs ) after cystocele repair . Methods : 126 women who underwent pelvic organ prolapse surgery including cystocele repair were r and omized to suprapubic or transurethral catheterization . At the third postoperative day , PRVs were measured . The number of women with PRV > 150 ml , need for prolonged catheterization , recatheterization , length of hospital stay , frequency of urinary tract infections and complications were determined . Results : PRVs exceeded 150 ml in 13 out of 64 ( 20 % ) and 14 out of 62 ( 23 % ) women in the suprapubic and transurethral group , respectively ( p = 0.76 ) . In the suprapubic group a higher rate of urine leakage was noted ( 27 vs. 7 % , p = 0.003 ) . 10 women ( 16 % ) allocated to the suprapubic group switched to transurethral catheterization , because of problems with the suprapubic catheter . No protocol deviations were reported in the transurethral group . Of the women in both groups , 9 % developed urinary tract infections ( p = 0.93 ) . Conclusions : Suprapubic catheterization was comparable to transurethral catheterization in the prevention of postoperative voiding dysfunction after vaginal prolapse surgery , but it was associated with a higher rate of complications 75 patients , needing a bladder drainage for nonurological indications and having sterile urines were studied after r and omization into two groups . In the first group , drained with an urethral catheter , urinary infection took place in 12 (= 30 % ) patients , while it was detected in 4 (= 11 % ) drained with a suprapubic catheter . In this latter group , patients felt more comfortable , had less pain ; the duration of urinary drainage and hospital stay was shorter Twenty-four patients who underwent radical hysterectomy and pelvic node dissection for cervical carcinoma were r and omized in a pilot study to compare continuous postoperative drainage by urethral and suprapubic catheters . There were no statistically significant differences in either the duration of continuous catheter drainage before the return of spontaneous voiding or the incidence of urinary tract infection in the two groups . Power calculations reveal that 628 patients require to be entered into each arm of a future study in order to be able to detect the former difference should it exist ( α = 0.05 , β = 0.2 , difference = 16 % of one s.d . ) and 41 in the latter ( α = 0.05 , β = 0.2 , 92.9 % urethral group had UTI , 70 % suprapubic group had UTI ) . We conclude that differences in these objective measures of catheter efficacy and morbidity between the groups , if they exist , are clinical ly irrelevant . On this basis we suggest that individual gynaecological oncologists should continue to use whichever method of catheter drainage best suits their clinical practice OBJECTIVE The purpose of this study was to compare the risk of significant bacteruria between clean intermittent self-catheterization ( CISC ) and suprapubic catheterization ( SPC ) after urogynecologic surgery . STUDY DESIGN Patients were r and omized to CISC or SPC . A urinalysis and patient satisfaction question naire were conducted on postoperative days 2 and 7 . Urine culture was performed for positive urinalysis . Significant bacteruria was defined as > 100,000 cfu/mL. To detect a decrease in bacteruria risk from 25 % to 10 % , 113 subjects per group were needed with 80 % power and alpha of 0.05 . RESULTS Of 248 r and omized patients , 210 were included in the final analysis . The overall risk of bacteruria was 27 % with no difference between SPC and CISC ( 31 % vs 23 % , P = .23 ) . Patients reported more frustration ( P = .01 ) and more difficulty ( P = .003 ) using CISC . CONCLUSION There was no difference in risk of significant bacteruria between CISC and SPC . Patients reported more frustration and difficulty with self-catheterization |
13,882 | 19,430,813 | Conclusion In conclusion , EGFR mutation and protein expression status may provide useful clinical information in terms of the likelihood of tumor response and disease prognosis . | Introduction The objective of this analysis was to examine the relationship between genomic variation and health outcomes in studies performed in non-small cell lung cancer ( NSCLC ) patients treated with single agent epidermal growth factor receptor-tyrosine kinase inhibitors ( EGFR-TKIs ) using a systematic review with statistical pooling of data . | BACKGROUND We conducted a r and omized , placebo-controlled , double-blind trial to determine whether the epidermal growth factor receptor inhibitor erlotinib prolongs survival in non-small-cell lung cancer after the failure of first-line or second-line chemotherapy . METHODS Patients with stage IIIB or IV non-small-cell lung cancer , with performance status from 0 to 3 , were eligible if they had received one or two prior chemotherapy regimens . The patients were stratified according to center , performance status , response to prior chemotherapy , number of prior regimens , and prior platinum-based therapy and were r and omly assigned in a 2:1 ratio to receive oral erlotinib , at a dose of 150 mg daily , or placebo . RESULTS The median age of the 731 patients who underwent r and omization was 61.4 years ; 49 percent had received two prior chemotherapy regimens , and 93 percent had received platinum-based chemotherapy . The response rate was 8.9 percent in the erlotinib group and less than 1 percent in the placebo group ( P<0.001 ) ; the median duration of the response was 7.9 months and 3.7 months , respectively . Progression-free survival was 2.2 months and 1.8 months , respectively ( hazard ratio , 0.61 , adjusted for stratification categories ; P<0.001 ) . Overall survival was 6.7 months and 4.7 months , respectively ( hazard ratio , 0.70 ; P<0.001 ) , in favor of erlotinib . Five percent of patients discontinued erlotinib because of toxic effects . CONCLUSIONS Erlotinib can prolong survival in patients with non-small-cell lung cancer after first-line or second-line chemotherapy PURPOSE In non-small-cell lung cancer ( NSCLC ) , clinical and biologic predictors for epidermal growth factor receptor ( EGFR ) tyrosine kinase inhibitor sensitivity have been identified in retrospective studies , and there is urgent need to vali date these results in prospect i ve trials . The ONCOBELL trial is a prospect i ve phase II study evaluating gefitinib sensitivity in NSCLC patients who never smoked or have increased EGFR gene copy number or activation of the antiapoptotic protein Akt . PATIENTS AND METHODS EGFR gene copy number was evaluated using fluorescence in situ hybridization ( FISH ) , and presence of phospho-Akt was evaluated using immunohistochemistry . Additional tests included immunohistochemistry analysis of EGFR , FISH analysis of HER2 , and mutation analysis of EGFR , HER2 , and K-ras . RESULTS From November 2004 to February 2006 , 183 patients were screened , and 42 patients were enrolled onto the trial . We observed one complete and 19 partial responses , for an overall response rate ( RR ) of 47.6 % ( 95 % CI , 32.5 % to 62.7 % ) . Median duration of response was 6.1 months , median time to progression ( TTP ) was 6.4 months , 1-year survival rate was 64.3 % , and median survival time was not reached . EGFR FISH-positive patients , compared with negative patients , had higher RR ( 68.0 % v 9.1 % , respectively ; P < .001 ) , longer TTP ( 7.6 v 2.7 months , respectively ; P = .02 ) , and a trend for longer survival ( median survival not reached v 7.4 months , respectively ; P = .3 ) . Therapy was well tolerated , and there were no drug-related deaths . Median follow-up time was too short for significance tests of differences in survival outcomes . CONCLUSION Gefitinib is active and well tolerated in patients with trial characteristics , and EGFR FISH analysis is an accurate predictor for such therapy Purpose : In patients with non – small cell lung cancer ( NSCLC ) , mutations in the epidermal growth factor receptor ( EGFR ) tyrosine kinase domain have been associated with sensitivity to erlotinib and gefitinib . We undertook this study to explore the relationship between EGFR mutation type and clinical variables , including treatment with gefitinib and erlotinib . Experimental Design : In patients with NSCLC , EGFR exon 19 deletion mutations and EGFR L858R point mutations were analyzed by nonsequencing PCR-based methods from paraffin blocks of tissue obtained before treatment . The results were correlated with clinical information ( sex , pathologic subtype , race/ethnicity , treatment , and overall survival ) . Results : The two most common EGFR mutations were identified in 24 % ( 70 of 291 ; 95 % confidence interval , 26%-38 % ) of tumors from patients with NSCLC . EGFR mutation was associated with Asian ethnicity ( P = 0.0023 ) and being a “ never smoker ” ( P = 0.0001 ) . Among patients with EGFR mutations , 39 % ( 27 of 70 ) had EGFR L858R , whereas 61 % ( 43 of 70 ) had an EGFR exon 19 deletion . After treatment with erlotinib ( n = 12 ) or gefitinib ( n = 22 ) , patients with EGFR mutations had a median overall survival of 20 months . After treatment with erlotinib or gefitinib , patients with EGFR exon 19 deletions had significantly longer median survival than patients with EGFR L858R ( 34 versus 8 months ; log-rank P = 0.01 ) . Conclusions : EGFR mutations in exons 19 or 21 are correlated with clinical factors predictive of response to gefitinib and erlotinib . Those with EGFR exon 19 deletion mutations had a longer median survival than patients with EGFR L858R point mutation . These observations warrant confirmation in a prospect i ve study and exploration of the biological mechanisms of the differences between the two major EGFR mutations PURPOSE Epidermal growth factor receptor ( EGFR ) mutations have been associated with tumor response to treatment with single-agent EGFR inhibitors in patients with relapsed non-small-cell lung cancer ( NSCLC ) . The implication s of EGFR mutations in patients treated with EGFR inhibitors plus first-line chemotherapy are unknown . KRAS is frequently activated in NSCLC . The relationship of KRAS mutations to outcome after EGFR inhibitor treatment has not been described . PATIENTS AND METHODS Previously untreated patients with advanced NSCLC in the phase III TRIBUTE study who were r and omly assigned to carboplatin and paclitaxel with erlotinib or placebo were assessed for survival , response , and time to progression ( TTP ) . EGFR exons 18 through 21 and KRAS exon 2 were sequenced in tumors from 274 patients . Outcomes were correlated with EGFR and KRAS mutations in retrospective subset analyses . RESULTS EGFR mutations were detected in 13 % of tumors and were associated with longer survival , irrespective of treatment ( P < .001 ) . Among erlotinib-treated patients , EGFR mutations were associated with improved response rate ( P < .05 ) and there was a trend toward an erlotinib benefit on TTP ( P = .092 ) , but not improved survival ( P = .96 ) . KRAS mutations ( 21 % of tumors ) were associated with significantly decreased TTP and survival in erlotinib plus chemotherapy-treated patients . CONCLUSION EGFR mutations may be a positive prognostic factor for survival in advanced NSCLC patients treated with chemotherapy with or without erlotinib , and may predict greater likelihood of response . Patients with KRAS-mutant NSCLC showed poorer clinical outcomes when treated with erlotinib and chemotherapy . Further studies are needed to confirm the findings of this retrospective subset analysis PURPOSE To evaluate the relationship between mutations of the epidermal growth factor receptor ( EGFR ) gene and the effectiveness of gefitinib treatment in patients with recurrent lung cancer after pulmonary resection . PATIENTS AND METHODS We sequenced exons 18 - 21 of the EGFR gene using total RNA extracted from 59 patients with lung cancer who were treated with gefitinib for recurrent lung cancer . Gefitinib effectiveness was evaluated by both imaging studies and change in serum carcinoembryonic antigen ( CEA ) levels . RESULTS EGFR mutations were found in 33 patients ( 56 % ) . Of these mutations , 17 were deletions around codons 746 - 750 and 15 were point mutations ( 12 at codon 858 , three at other codons ) , and one was an insertion . EGFR mutations were significantly more prevalent in females , adenocarcinoma , and never-smokers . Gefitinib treatment result ed in tumor shrinkage and /or CEA decrease to less than half of the baseline level in 26 patients , tumor growth and /or CEA elevation in 24 patients , and gefitinib effect was not assessable in nine patients . Female , never-smoking patients with adenocarcinoma tended to respond better to gefitinib treatment . Gefitinib was effective in 24 of 29 patients with EGFR mutations , compared with two of 21 patients without mutations ( P < .0001 ) . Of note , del746 - 750 might be superior to L858R mutations for prediction of gefitinib response . Patients with EGFR mutations survived for a longer period than those without the mutations after initiation of gefitinib treatment ( P = .0053 ) . CONCLUSION EGFR mutations were a good predictor of clinical benefit of gefitinib in this setting Purpose : Erlotinib has proven activity in pretreated patients with advanced non – small cell lung cancer ( NSCLC ) . We evaluated erlotinib in the frontline treatment of advanced NSCLC and assessed biological predictors of outcome . Experimental Design : In this phase II study , chemotherapy-naive patients with stage IIIB/IV NSCLC received oral erlotinib ( 150 mg/d ) until disease progression or unacceptable toxicity occurred . Tumor response was assessed every 6 weeks , and sample s were analyzed for potential molecular markers of treatment response and survival . The primary end point was the proportion of patients without disease progression after 6 weeks of treatment . Results : Fifty-three patients were eligible . The overall rate of nonprogression at 6 weeks was 52.8 % ( 28 of 53 patients ) . Tumor response rate was 22.7 % , with 1 complete response , 11 partial responses , and 16 cases of stable disease . Responses were seen across most patient clinical characteristics . The median duration of tumor response was 333 days ; median overall survival was 391 days ; and median time to disease progression was 84 days . Erlotinib was well tolerated , the main treatment-related adverse events being mild-to-moderate rash and diarrhea . Histologic material for biological studies was available in 29 cases . Four of five responders and one patient with stable disease had a classic epidermal growth factor receptor tyrosine kinase mutation . Two progressing patients exhibited epidermal growth factor receptor point mutations ( one with T790 M mutation ) , and K-ras mutations were detected in 10 nonresponders . Conclusions : Erlotinib shows significant antitumor activity in the first-line treatment of advanced NSCLC and may be a viable alternative to chemotherapy . Patient selection can not easily be based on clinical or biological variables PURPOSE The phase III Iressa Survival Evaluation in Lung Cancer ( ISEL ) trial compared gefitinib with placebo in 1,692 patients with refractory advanced non-small-cell lung cancer . We analyzed ISEL tumor biopsy sample s to examine relationships between biomarkers and clinical outcome after gefitinib treatment in a placebo-controlled setting . METHODS Biomarkers included epidermal growth factor receptor ( EGFR ) gene copy number by fluorescence in situ hybridization ( n = 370 ) ; EGFR ( n = 379 ) and phosphorylated Akt ( p-Akt ) protein expression ( n = 382 ) by immunohistochemistry ; and mutations in EGFR ( n = 215 ) , KRAS ( n = 152 ) , and BRAF ( n = 118 ) . RESULTS High EGFR gene copy number was a predictor of a gefitinib-related effect on survival ( hazard ratio [ HR ] , 0.61 for high copy number and HR , 1.16 for low copy number ; comparison of high v low copy number HR , P = .045 ) . EGFR protein expression was also related to clinical outcome ( HR for positive , 0.77 ; HR for negative , 1.57 ; comparison of high v low protein expression HR , P = .049 ) . Patients with EGFR mutations had higher response rates than patients without EGFR mutations ( 37.5 % v 2.6 % ) ; there were insufficient data for survival analysis . No relationship was observed between p-Akt protein expression and survival outcome , and the limited amount of data collected for KRAS and BRAF mutations prevented any meaningful evaluation of clinical outcomes in relation to these mutations . CONCLUSION EGFR gene copy number was a predictor of clinical benefit from gefitinib in ISEL . Additional studies are warranted to assess these biomarkers fully for the identification of patients most likely to benefit from gefitinib treatment PURPOSE This is a phase II , multicenter , open-label study of chemotherapy-naïve patients with non-small-cell lung cancer ( NSCLC ) and age > or = 70 years who were treated with erlotinib and evaluated to determine the median , 1-year , and 2-year survival . The secondary end points include radiographic response rate , time to progression ( TTP ) , toxicity , and symptom improvement . PATIENTS AND METHODS Eligible patients with NSCLC were treated with erlotinib 150 mg/d until disease progression or significant toxicity . Tumor response was assessed every 8 weeks by computed tomography scan using Response Evaluation Criteria in Solid Tumors . Tumor sample s were analyzed for the presence of somatic mutations in EGFR and KRAS . RESULTS Eighty eligible patients initiated erlotinib therapy between March 2003 and May 2005 . There were eight partial responses ( 10 % ) , and an additional 33 patients ( 41 % ) had stable disease for 2 months or longer . The median TTP was 3.5 months ( 95 % CI , 2.0 to 5.5 months ) . The median survival time was 10.9 months ( 95 % CI , 7.8 to 14.6 months ) . The 1- and 2- year survival rates were 46 % and 19 % , respectively . The most common toxicities were acneiform rash ( 79 % ) and diarrhea ( 69 % ) . Four patients developed interstitial lung disease of grade 3 or higher , with one treatment-related death . EGFR mutations were detected in nine of 43 patients studied . The presence of an EGFR mutation was strongly correlated with disease control , prolonged TTP , and survival . CONCLUSION Erlotinib monotherapy is active and relatively well tolerated in chemotherapy-naïve elderly patients with advanced NSCLC . Erlotinib merits consideration for further investigation as a first-line therapeutic option in elderly patients PURPOSE We conducted a phase II study of single agent treatment with gefitinib in chemotherapy-naïve patients with advanced non-small-cell lung cancer ( NSCLC ) to assess its efficacy and toxicity . PATIENTS AND METHODS Patients received 250 mg doses of gefitinib daily . Administration of gefitinib was terminated if partial response ( PR ) was not achieved within 8 weeks or if tumor reduction was not observed within 4 weeks . In these cases , platinum-based doublet chemotherapy was given as a salvage treatment . We evaluated mutation status of the epidermal growth factor receptor ( EGFR ) gene in cases with available tumor sample s. RESULTS Forty-two patients were enrolled between March and November 2003 , with 40 of these patients being eligible . The response rate was 30 % ( 95 % CI , 17 % to 47 % ) . The most common toxicity included grade 1 or 2 acne-like rash ( 50 % ) and grade 1 diarrhea ( 18 % ) . Grade 2 or 3 hepatic toxicity was observed in 8 % of patients . Four patients developed grade 5 interstitial lung disease ( ILD ) . Thirty patients received second-line chemotherapy . Median survival time was 13.9 months ( 95 % CI , 9.1 to 18.7 months ) , and the 1-year survival rate was 55 % . Tumor sample s were available in 13 patients , including four cases of PR , six cases of stable disease , and three cases of progressive disease . EGFR mutations ( deletions in exon 19 or point mutations [ L858R or E746V ] ) were detected in four tumor tissues . All four patients with EGFR mutation achieved PR with gefitinib treatment . CONCLUSION Single agent treatment with gefitinib is active in chemotherapy-naïve patients with advanced NSCLC , but produces unacceptably frequent ILD in the Japanese population PURPOSE Most cases of non-small-cell lung cancer ( NSCLC ) with dramatic responses to gefitinib have specific activating mutations in the epidermal growth factor receptor ( EGFR ) , but the predictive value of these mutations has not been defined in large clinical trials . The goal of this study was to determine the contribution of molecular alterations in EGFR to response and survival within the phase II ( IDEAL ) and phase III ( INTACT ) trials of gefitinib . PATIENTS AND METHODS We analyzed the frequency of EGFR mutations in lung cancer specimens from both the IDEAL and INTACT trials and compared it with EGFR gene amplification , another genetic abnormality in NSCLC . RESULTS EGFR mutations correlated with previously identified clinical features of gefitinib response , including adenocarcinoma histology , absence of smoking history , female sex , and Asian ethnicity . No such association was seen in patients whose tumors had EGFR amplification , suggesting that these molecular markers identify different biologic subsets of NSCLC . In the IDEAL trials , responses to gefitinib were seen in six of 13 tumors ( 46 % ) with an EGFR mutation , two of seven tumors ( 29 % ) with amplification , and five of 56 tumors ( 9 % ) with neither mutation nor amplification ( P = .001 for either EGFR mutation or amplification v neither abnormality ) . Analysis of the INTACT trials did not show a statistically significant difference in response to gefitinib plus chemotherapy according to EGFR genotype . CONCLUSION EGFR mutations and , to a lesser extent , amplification appear to identify distinct subsets of NSCLC with an increased response to gefitinib . The combination of gefitinib with chemotherapy does not improve survival in patients with these molecular markers |
13,883 | 29,775,501 | There was limited ( low to very low- quality ) evidence of an effect for all growth outcomes .
Quality of evidence There is moderate to very low- quality evidence that educational interventions can improve complementary feeding practice s but insufficient evidence to conclude that it impacts growth outcomes .
AUTHORS ' CONCLUSIONS Overall , we found evidence that education improves complementary feeding practice | BACKGROUND Although complementary feeding is a universal practice , the methods and manner in which it is practice d vary between cultures , individuals and socioeconomic classes .
The period of complementary feeding is a critical time of transition in the life of an infant , and inappropriate complementary feeding practice s , with their associated adverse health consequences , remain a significant global public health problem .
Educational interventions are widely acknowledged as effective in promoting public health strategy , and those aim ed at improving complementary feeding practice s provide information about proper complementary feeding practice s to caregivers of infants/children .
It is therefore important to summarise evidence on the effectiveness of educational interventions to improve the complementary feeding practice s of caregivers of infants .
OBJECTIVES To assess the effectiveness of educational interventions for improving the complementary feeding ( weaning ) practice s of primary caregivers of children of complementary feeding age , and related health and growth outcomes in infants . | Background As a result of inappropriate feeding , poor health and hygiene , and poor caring practice s , the nutritional status of many young infants deteriorates with advancing age . Objective To explore the effectiveness of a nutrition education package to prevent malnutrition among young children . Methods A community-based , r and omized , controlled trial was conducted among 605 normal and mildly malnourished children aged 6 to 9 months in 121 Community Nutrition Centers ( CNCs ) of the Bangladesh Integrated Nutrition Project ( BINP ) in four regions of Bangladesh from 2000 to 2002 . The intervention group received weekly nutrition education based on the nutrition triangle concept of UNICEF for 6 months , whereas the control group received regular BINP services . Both groups were observed for a further 6 months to assess the sustainability of the effects . Information on socio-economic status , feeding patterns , morbidity , and anthropometric features was collected . Results A significant increase in the frequency of complementary feeding was observed in the intervention group as compared with the control group , and the increase was sustained throughout the observation period . The intervention group had a higher weight gain than the control group after the end of the intervention ( 0.86 vs. 0.77 kg , p = 0.053 ) and after the end of the observation period ( 1.81 vs. 1.39 kg , p < .001 ) . The proportion of normal and mildly malnourished children was greater in the intervention group than in the control group after the end of the observations ( 88.9 % vs. 61.5 % , p < .001 ) . Nutrition education successfully prevented malnutrition in all the areas . Variation in the outcome of nutrition education among the regions was observed . Conclusions This culturally appropriate nutrition education package based on the nutrition triangle model effectively prevented growth faltering and malnutrition among young children ABSTRACT OBJECTIVE To assess the effect of educational dietary intervention offered in the child ’s first year of life , as well as teenage mothers and gr and mothers in carrying out the dietary recommendations at four to seven years . METHODS R and omized clinical trial initiated in 2006 , in Porto Alegre , RS , involving 323 teenage mothers and gr and mothers who cohabited . The intervention consisted of six counseling sessions on breastfeeding and healthy complementary feeding . The first session occurred in the maternity ward and the other ones in the households of mothers at seven , 15 , 30 , 60 , and 120 days of the child ’s life . The information about the child ’s diet were obtained on a monthly basis in the first six months , every two months in the second half-year , and at four to seven years , using a food frequency question naire . To assess the adequacy of food consumption to the recommendations from the Ministry of Health , we elaborated a score system that would reflect the compliance with the Ten Steps for Healthy Toddlers from 2 to 10 Years . The average scores of intervention and control groups were compared using the t-test . RESULTS Low adherence to recommendations on child nutrition was found in the study population , with no difference in implementation the steps between the groups . The score on the compliance with the steps was similar in both groups ( 9.6 [ SD = 1.63 ] and 9.3 [ SD = 1.60 ] in the intervention and control groups , respectively ) and no influence of the cohabitation with the gr and mother was found . CONCLUSIONS Educational dietary intervention in the first four months of the child ’s life for teenage mothers and gr and mothers had no effect on the compliance with the recommendations at four to seven years of the child ’s life Summary Background Many countries now offer support to teenage mothers to help them to achieve long-term socioeconomic stability and to give a successful start to their children . The Family Nurse Partnership ( FNP ) is a licensed intensive home-visiting intervention developed in the USA and introduced into practice in Engl and that involves up to 64 structured home visits from early pregnancy until the child 's second birthday by specially recruited and trained family nurses . We aim ed to assess the effectiveness of giving the programme to teenage first-time mothers on infant and maternal outcomes up to 24 months after birth . Methods We did a pragmatic , non-blinded , r and omised controlled , parallel-group trial in community midwifery setting s at 18 partnerships between local authorities and primary and secondary care organisations in Engl and . Eligible participants were nulliparous and aged 19 years or younger , and were recruited at less than 25 weeks ' gestation . Field-based research ers r and omly allocated mothers ( 1:1 ) via remote r and omisation ( telephone and web ) to FNP plus usual care ( publicly funded health and social care ) or to usual care alone . Allocation was stratified by site and minimised by gestation ( < 16 weeks vs ≥16 weeks ) , smoking status ( yes vs no ) , and preferred language of data collection ( English vs non-English ) . Mothers and assessors ( local research ers at baseline and 24 months ' follow-up ) were not masked to group allocation , but telephone interviewers were blinded . Primary endpoints were biomarker-calibrated self-reported tobacco use by the mother at late pregnancy , birthweight of the baby , the proportion of women with a second pregnancy within 24 months post-partum , and emergency attendances and hospital admissions for the child within 24 months post-partum . Analyses were by intention to treat . This trial is registered with IS RCT N , number IS RCT N23019866 . Findings Between June 16 , 2009 , and July 28 , 2010 , we screened 3251 women . After enrolment , 823 women were r and omly assigned to receive FNP and 822 to usual care . All follow-up data were retrieved by April 25 , 2014 . 304 ( 56 % ) of 547 women assigned to FNP and 306 ( 56 % ) of 545 assigned to usual care smoked at late pregnancy ( adjusted odds ratio [ AOR ] 0·90 , 97·5 % CI 0·64–1·28 ) . Mean birthweight of 742 babies with mothers assigned to FNP was 3217·4 g ( SD 618·0 ) , whereas birthweight of 768 babies assigned to usual care was 3197·5 g ( SD 581·5 ; adjusted mean difference 20·75 g , 97·5 % CI −47·73 to 89·23 . 587 ( 81 % ) of 725 assessed children with mothers assigned to FNP and 577 ( 77 % ) of 753 assessed children assigned to usual care attended an emergency department or were admitted to hospital at least once before their second birthday ( AOR 1·32 , 97·5 % CI 0·99–1·76 ) . 426 ( 66 % ) of 643 assessed women assigned to FNP and 427 ( 66 % ) 646 assigned to usual care had a second pregnancy within 2 years ( AOR 1·01 , 0·77–1·33 ) . At least one serious adverse event ( mainly clinical events associated with pregnancy and infancy period ) was reported for 310 ( 38 % ) of 808 participants ( mother – child ) in the usual care group and 357 ( 44 % ) of 810 in the FNP group , none of which were considered related to the intervention . Interpretation Adding FNP to the usually provided health and social care provided no additional short-term benefit to our primary outcomes . Programme continuation is not justified on the basis of available evidence , but could be reconsidered should supportive longer-term evidence emerge . Funding Department of Health Policy Research Programme OBJECTIVE To assess the impact of a child feeding training program for primary care health professionals about breastfeeding and complementary feeding practice s. METHODS Cluster-r and omized field trial conducted in the city of Porto Alegre , ( RS ) , Brazil . Twenty primary health care centers ( HCC ) were r and omized into intervention ( n = 9 ) and control ( n = 11 ) groups . The health professionals ( n = 200 ) at the intervention group centers received training about healthy feeding practice s. Pregnant women were enrolled at the study . Up to six months of child 's age , home visits were made to obtain variables related to breastfeeding and introduction of foods . RESULTS 619 children were evaluated : 318 from the intervention group and 301 from the control group . Exclusive breastfeeding prevalence in the first ( 72.3 versus 59.4 % ; RR = 1.21 ; 95%CI 1.08 - 1.38 ) , second ( 62.6 versus 48.2 % ; RR = 1.29 ; 95%CI 1.10 - 1.53 ) , and third months of life ( 44.0 % versus 34.6 % ; RR = 1.27 ; 95%CI 1.04 - 1.56 ) was higher in the intervention group compared to the control group . The prevalence of children who consumed meat four or five times per week was higher in the intervention group than in the control group ( 36.8 versus 22.6 % ; RR = 1.62 ; 95%CI 1.32 - 2.03 ) . The prevalence of children who had consumed soft drinks ( 34.9 versus 52.5 % ; RR = 0.66 ; 95%CI 0.54 - 0.80 ) , chocolate ( 24.5 versus 36.7 % RR = 0.66 95%CI 0.53 - 0.83 ) , petit suisse ( 68.9 versus 79.7 ; 95%CI 0.75 - 0.98 ) and coffee ( 10.4 versus 20.1 % ; RR = 0.51 ; 95%CI 0.31 - 0.85 ) in their six first months of life was lower in the intervention group . CONCLUSION The training of health professionals had a positive impact on infant feeding practice s , contributing to the promotion of child health The WHO ( 2001 ) recommends exclusive breast-feeding and delaying the introduction of solid foods to an infant 's diet until 6 months postpartum . However , in many countries , this recommendation is followed by few mothers , and earlier weaning onto solids is a commonly reported global practice . Therefore , this prospect i ve , observational study aim ed to assess compliance with the WHO recommendation and examine weaning practice s , including the timing of weaning of infants , and to investigate the factors that predict weaning at ≤ 12 weeks . From an initial sample of 539 pregnant women recruited from the Coombe Women and Infants University Hospital , Dublin , 401 eligible mothers were followed up at 6 weeks and 6 months postpartum . Quantitative data were obtained on mothers ' weaning practice s using semi-structured question naires and a short dietary history of the infant 's usual diet at 6 months . Only one mother ( 0.2 % ) complied with the WHO recommendation to exclusively breastfeed up to 6 months . Ninety-one ( 22.6 % ) infants were prematurely weaned onto solids at ≤ 12 weeks with predictive factors after adjustment , including mothers ' antenatal reporting that infants should be weaned onto solids at ≤ 12 weeks , formula feeding at 12 weeks and mothers ' reporting of the maternal gr and mother as the principal source of advice on infant feeding . Mothers who weaned their infants at ≤ 12 weeks were more likely to engage in other sub-optimal weaning practice s , including the addition of non-recommended condiments to their infants ' foods . Provision of professional advice and exploring antenatal maternal misperceptions are potential areas for targeted interventions to improve compliance with the recommended weaning practice The effectiveness of in-hospital self-care patient education , delivered to patients following heart surgery , is question able , as evidence indicates individuals are not able to absorb and /or retain information at this time . In the absence of adequate instruction , individuals will not have the relevant information to engage in specific self-care behaviors , result ing in the onset of complications and /or hospital readmissions . The purpose of this pilot study was to collect preliminary evidence to demonstrate the impact of an individualized education intervention given above and beyond usual care , delivered , at two points in time , following hospital discharge . A r and omized controlled trial was used in which 34 patients were r and omly assigned to one of two groups . Chi-square analyses to examine differences between groups on complications and hospital readmission rates were conducted . Findings point to the impact of the intervention in reducing the number of hospital readmissions and complications at 3 months following hospital discharge Background Many HIV/AIDS patients experience pain often due to advanced HIV/AIDS infection and side effects of treatment . In sub-Saharan Africa , pain management for people with HIV/AIDS is suboptimal . With survival extended as a direct consequence of improved access to antiretroviral therapy , the prevalence of HIV/AIDS related pain is increasing . As most care is provided at home , the management of pain requires patient and family involvement . Pain education is an important aspect in the management of pain in HIV/AIDS patients . Studies of the effectiveness of pain education interventions for people with HIV/AIDS have been conducted almost exclusively in western countries . Methods / design A r and omised controlled trial is being conducted at the HIV and palliative care clinics of two public hospitals in Malawi . To be eligible , patient participants must have a diagnosis of HIV/AIDS ( stage III or IV ) . Carer participants must be the individual most involved in the patient ’s unpaid care . Eligible participants are r and omised to either : ( 1 ) a 30-minute face-to-face educational intervention covering pain assessment and management , augmented by a leaflet and follow-up telephone call at two weeks ; or ( 2 ) usual care . Those allocated to the usual care group receive the educational intervention after follow-up assessment s have been conducted ( wait-list control group ) . The primary outcome is pain severity measured by the Brief Pain Inventory . Secondary outcomes are pain interference , patient knowledge of pain management , patient quality of life , carer knowledge of pain management , caregiver motivation and carer quality of life . Follow-up assessment s are conducted eight weeks after r and omisation by palliative care nurses blind to allocation . Discussion This r and omised controlled trial conducted in sub-Saharan Africa among people living with HIV/AIDS and their carers will assess whether a pain education intervention is effective in reducing pain and improving pain management , quality of life and carer motivation . Trial registration Current Controlled Trials IS RCT N72861423 OBJECTIVE To determine the effectiveness of an educational intervention on infant feeding behaviors and mothers ' psychosocial mediating variables based on the Theory of Planned Behavior ( TPB ) , and to assess the predictive effect of mediating variables on mothers ' intention and feeding practice s. METHODS We did a cluster-r and omized trial in 8 paired townships of Laishui County , China during 2006 - 2007 . 599 mothers with infants aged 2 - 4-mo were enrolled at the baseline survey , of whom 485 were followed up after 11-mo intervention . RESULTS The intervention group had significantly higher scores than controls in knowledge , attitudes , self-efficacy , intention , norm beliefs , as well as feeding behaviors ( Hotellings T-square=143.96 , P<0.01 ) . Mothers ' intention towards recommended feeding behaviors was positively associated with mothers ' attitudes , subjective norms and self-efficacy at baseline , and was associated with their attitudes , self-efficacy , and knowledge at post-intervention evaluation . Intervention , mothers ' knowledge , intention and subjective norm of villagers were independent predictors of their feeding behaviors after intervention . CONCLUSIONS Findings from this study suggested that TPB is an appropriate theory for explaining the effect of psychosocial factors such as knowledge , attitudes , self-efficacy , subjective norms , and intentions on infant feeding behaviors , and a useful guideline to design the targets and key approaches for infant feeding interventions Summary Background Around 30 % of the world 's stunted children live in India . The Government of India has proposed a new cadre of community-based workers to improve nutrition in 200 districts . We aim ed to find out the effect of such a worker carrying out home visits and participatory group meetings on children 's linear growth . Methods We did a cluster-r and omised controlled trial in two adjoining districts of Jharkh and and Odisha , India . 120 clusters ( around 1000 people each ) were r and omly allocated to intervention or control using a lottery . R and omisation took place in July , 2013 , and was stratified by district and number of hamlets per cluster ( 0 , 1–2 , or ≥3 ) , result ing in six strata . In each intervention cluster , a worker carried out one home visit in the third trimester of pregnancy , monthly visits to children younger than 2 years to support feeding , hygiene , care , and stimulation , as well as monthly women 's group meetings to promote individual and community action for nutrition . Participants were pregnant women identified and recruited in the study clusters and their children . We excluded stillbirths and neonatal deaths , infants whose mothers died , those with congenital abnormalities , multiple births , and mother and infant pairs who migrated out of the study area permanently during the trial period . Data collectors visited each woman in pregnancy , within 72 h of her baby 's birth , and at 3 , 6 , 9 , 12 , and 18 months after birth . The primary outcome was children 's length-for-age Z score at 18 months of age . Analyses were by intention to treat . Due to the nature of the intervention , participants and the intervention team were not masked to allocation . Data collectors and the data manager were masked to allocation . The trial is registered as ISCRTN ( 51505201 ) and with the Clinical Trials Registry of India ( number 2014/06/004664 ) . Results Between Oct 1 , 2013 , and Dec 31 , 2015 , we recruited 5781 pregnant women . 3001 infants were born to pregnant women recruited between Oct 1 , 2013 , and Feb 10 , 2015 , and were therefore eligible for follow-up ( 1460 assigned to intervention ; 1541 assigned to control ) . Three groups of children could not be included in the final analysis : 147 migrated out of the study area ( 67 in intervention clusters ; 80 in control clusters ) , 77 died after the neonatal period and before 18 months ( 31 in intervention clusters ; 46 in control clusters ) , and seven had implausible length-for-age Z scores ( < –5 SD ; one in intervention cluster ; six in control clusters ) . We measured 1253 ( 92 % ) of 1362 eligible children at 18 months in intervention clusters , and 1308 ( 92 % ) of 1415 eligible children in control clusters . Mean length-for-age Z score at 18 months was −2·31 ( SD 1·12 ) in intervention clusters and −2·40 ( SD 1·10 ) in control clusters ( adjusted difference 0·107 , 95 % CI −0·011 to 0·226 , p=0·08 ) . The intervention did not significantly affect exclusive breastfeeding , timely introduction of complementary foods , morbidity , appropriate home care or care-seeking during childhood illnesses . In intervention clusters , more pregnant women and children attained minimum dietary diversity ( adjusted odds ratio [ aOR ] for women 1·39 , 95 % CI 1·03–1·90 ; for children 1·47 , 1·07–2·02 ) , more mothers washed their h and s before feeding children ( 5·23 , 2·61–10·5 ) , fewer children were underweight at 18 months ( 0·81 , 0·66–0·99 ) , and fewer infants died ( 0·63 , 0·39–1·00 ) . Interpretation Introduction of a new worker in areas with a high burden of undernutrition in rural eastern India did not significantly increase children 's length . However , certain secondary outcomes such as self-reported dietary diversity and h and washing , as well as infant survival were improved . The interventions tested in this trial can be further optimised for use at scale , but substantial improvements in growth will require investment in nutrition-sensitive interventions , including clean water , sanitation , family planning , girls ' education , and social safety nets . Funding UK Medical Research Council , Wellcome Trust , UK Department for International Development ( DFID ) Research suggests that repeatedly offering infants a variety of vegetables during weaning increases vegetable intake and liking . The effect may extend to novel foods . The present study aim ed to investigate the impact of advising parents to introduce a variety of single vegetables as first foods on infants ' subsequent acceptance of a novel vegetable . Mothers of 4- to 6-month-old infants in the UK , Greece and Portugal were r and omised to either an intervention group ( n 75 ) , who received guidance on introducing five vegetables ( one per d ) as first foods repeated over 15 d , or a control group ( n 71 ) who received country-specific ' usual care ' . Infant 's consumption ( g ) and liking ( maternal and research er rated ) of an unfamiliar vegetable were assessed 1 month post-intervention . Primary analyses were conducted for the full sample with secondary analyses conducted separately by country . No significant effect of the intervention was found for vegetable intake in the three countries combined . However , sub-group analyses showed that UK intervention infants consumed significantly more novel vegetable than control infants ( 32.8 ( SD 23.6 ) v. 16.5 ( sd 12.1 ) g ; P = 0.003 ) . UK mothers and research ers rated infants ' vegetable liking higher in the intervention than in control condition . In Portugal and Greece , there was no significant intervention effect on infants ' vegetable intake or liking . The differing outcome between countries possibly reflects cultural variations in existing weaning practice s. However , the UK results suggest in countries where vegetables are not common first foods , advice on introducing a variety of vegetables early in weaning may be beneficial for increasing vegetable acceptance OBJECTIVE To describe the introduction of complementary foods in a population -based cohort in relation to recommendations and explore the possible impact of maternal education on infant feeding practice s. DESIGN Prospect i ve data from the All Babies in Southeast Sweden ( ABIS ) cohort study were used . The ABIS study invited all infants born in south-east Sweden during October 1997-October 1999 ( n 21 700 ) to participate . A question naire was completed for 16 022 infants . During the infants ' first year parents continuously filed in a diary covering introduction of foods . SETTING Sweden . SUBJECTS Infants ( n 9727 ) with completed food diaries . RESULTS Potatoes , vegetables , fruits/berries and porridge were the foods first introduced , with a median introduction between 19 and 22 weeks , followed by introduction of meat , cow 's milk , follow-on formula and sour milk/yoghurt between 24 and 27 weeks . Early introduction of any food , before 16 weeks , occurred for 27 % of the infants and was more common in infants of mothers with low education . Overall , potatoes ( 14·7 % ) , vegetables ( 11·1 % ) , fruits/berries ( 8·5 % ) , porridge ( 7·4 % ) and follow-on formula ( 2·7 % ) were the foods most frequently introduced early . The majority of infants ( ≥70 % ) were introduced to potatoes , vegetables , fruits/berries and porridge during concurrent breast-feeding , but introduction during concurrent breast-feeding was less common in infants of mothers with low education . CONCLUSIONS Most infants were introduced to complementary foods timely in relation to recommendations . Low maternal education was associated with earlier introduction of complementary foods and less introduction during concurrent breast-feeding . Still , the results indicated exposure to fewer foods at 12 months in infants of mothers with low education It is unclear whether a substantial decline in malnutrition among infants in developing countries can be achieved by increasing food availability and nutrition counseling without concurrent morbidity-reducing interventions . The study was design ed to determine whether provision of generous amounts of a micronutrient-fortified food supplement supported by counseling or nutritional counseling alone would significantly improve physical growth between 4 and 12 mo of age . In a controlled trial , 418 infants 4 mo of age were individually r and omized to one of the four groups and followed until 12 mo of age . The first group received a milk-based cereal and nutritional counseling ; the second group monthly nutritional counseling alone . To control for the effect of twice-weekly home visits for morbidity ascertainment , similar visits were made in one of the control groups ( visitation group ) ; the fourth group received no intervention . The median energy intake from nonbreast milk sources was higher in the food supplementation group than in the visitation group by 1212 kJ at 26 wk ( P < 0.001 ) , 1739 kJ at 38 wk ( P < 0.001 ) and 2257 kJ at 52 wk ( P < 0.001 ) . The food supplementation infants gained 250 g ( 95 % confidence interval : 20 - -480 g ) more weight than did the visitation group . The difference in the mean increment in length during the study was 0.4 cm ( 95 % confidence interval : -0.1 - -0.9 cm ) . The nutritional counseling group had higher energy intakes ranging from 280 to 752 kJ at different ages ( P < 0.05 at all ages ) but no significant benefit on weight and length increments . Methods to enhance the impact of these interventions need to be identified Background Childhood overweight and obesity is a global public health challenge . Primary prevention initiatives targeting parents have been called for to encourage a positive feeding environment and healthy eating habits that may lay a good foundation for future health . At the same time , there is a need for interventions which combine accessibility and scalability with cost effectiveness . Today ’s parents are extensive Internet-users , but only a few r and omized controlled trials have investigated the use of Internet to promote healthy eating habits in early childhood . In Early Food for Future Health we have developed and will evaluate an Internet-based tool for parents of children between 6 and 12 months , aim ing to increase knowledge about infant nutrition and foster protective feeding behavior . Methods During springtime 2016 , parents of children aged between 3 and 5 months were recruited through Norwegian child health centres and announcements on Facebook . After completing the baseline question naire , 718 parents were individually r and omized to intervention- or control group . The intervention group received monthly emails with links to an age-appropriate web-site when their child was between 6 and 12 months . The control group received ordinary care from the child health centres . The data - collection is ongoing . All participants will be followed up at ages 12 and possibly 24 and 48 months , with question naires relating to eating behaviour and feeding practice s , food variety and diet quality . Discussion Providing guidance and counseling to parents of infants is an important task for health authorities and the public child health services . Early Food for Future health is an intervention focusing on promoting early healthy food-habits which may prevent childhood overweight and obesity . If proven to be effective , Early Food for Future Health can be used by parents and public health nurses for supplementary guidance on feeding practice s and diet . This study has the potential to provide greater insight and underst and ing regarding early parental feeding practice s , child eating behavior and the development and efficacy of Internet-based public health interventions .Trial registration IS RCT N13601567 BACKGROUND A previous study in Pakistan assessed the effectiveness of delivering responsive stimulation and enhanced nutrition interventions to young children . Responsive stimulation significantly improved children 's cognitive , language , and motor development at 2 years of age . Both interventions significantly improved parenting skills , with responsive stimulation showing larger effects . In this follow-up study , we investigated whether interventions had benefits on children 's healthy development and care at 4 years of age . METHODS We implemented a follow-up study of the initial , community-based cluster-r and omised effectiveness trial , which was conducted through the Lady Health Worker programme in Sindh , Pakistan . We re-enrolled 1302 mother-child dyads ( 87 % of the 1489 dyads in the original enrolment ) for assessment when the child was 4 years of age . The children were originally r and omised in the following groups : nutrition education and multiple micronutrient powders ( enhanced nutrition ; n=311 ) , responsive stimulation ( n=345 ) , combined responsive stimulation and enhanced nutrition ( n=315 ) , and routine health and nutrition services ( control ; n=331 ) . The data collection team were masked to the allocated intervention . The original enrolment period included children born in the study area between April 1 , 2009 , and March 31 , 2010 , if they were up to 2·5 months old without signs of severe impairments . The primary endpoints for children were development and growth at 4 years of age . Interventions were given in monthly group sessions and in home visits . The primary endpoint for mothers was wellbeing and caregiving knowledge , practice s , and skills when the child was 4 years of age . Analysis was by intention to treat . The original trial is registered with Clinical Trials.gov , number NCT00715936 . FINDINGS 1302 mother-child dyads were re-enrolled between Jan 1 , 2013 , and March 31 , 2013 , all of whom were followed up at 4 years of age . Children who received responsive stimulation ( with or without enhanced nutrition ) had significantly higher cognition , language , and motor skills at 4 years of age than children who did not receive responsive stimulation . For children who received responsive stimulation plus enhanced nutrition , effect sizes ( Cohen 's d ) were 0·1 for IQ ( mean difference from control 1·2 , 95 % CI -0·3 to 2·7 ) , 0·3 for executive functioning ( 0·18 , -0·07 to 0·29 ) , 0·5 for pre-academic skills ( 7·53 , 5·14 to 9·92 ) and 0·2 for pro-social behaviours ( 0·08 , 0·03 to 0·13 ) . For children who received responsive stimulation alone , effect sizes were 0·1 for IQ ( mean difference with controls 1·7 , -0·3 to 3·7 ) , 0·3 for executive functioning ( 0·17 , 0·07 to 0·27 ) , 0·2 for pre-academic skills ( 3·86 , 1·41 to 6·31 ) , and 0·2 for pro-social behaviours ( 0·07 , 0·02 to 0·12 ) . Enhanced nutrition improved child motor development , with effect size of 0·2 for responsive stimulation plus enhanced nutrition ( 0·56 , -0·03 to 1·15 ) , and for enhanced nutrition alone ( 0·82 , 0·18 to 1·46 ) . Mothers who received responsive stimulation ( with or without enhanced nutrition ) had significantly better responsive caregiving behaviours at 4 years of child age than those who did not receive intervention . Effect size was 0·3 for responsive stimulation plus enhanced nutrition ( 1·95 , 0·75 to 3·15 ) and 0·2 for responsive stimulation ( 2·01 , 0·74 to 3·28 ) . The caregiving environment had a medium effect size of 0·3 for all interventions ( responsive stimulation plus enhanced nutrition 2·99 , 1·50 to 4·48 ; responsive stimulation alone 2·82 , 1·21 to 4·43 ; enhanced nutrition 3·52 , 1·70 to 5·34 ) . INTERPRETATION Responsive stimulation delivered in a community health service can improve child development and care , 2 years after the end of intervention . Future analyses of these data are needed to identify which children and families benefit more or less over time . FUNDING Gr and Challenges Canada To assess the impact on child growth of the nutrition-counseling component of the Integrated Management of Childhood Illnesses ( IMCI ) strategy , a r and omized trial was implemented . All 28 government health centers in a Southern Brazil city were paired according to baseline nutritional indicators . One center from each pair was r and omly selected and its doctors received 20-h training in nutrition counseling . Thirty-three doctors were included and 12 - 13 patients < 18 mo of age from each doctor were recruited . The study included testing the knowledge of doctors , observing consultations and visiting the children at home 8 , 45 and 180 d after the initial consultation . Maternal knowledge , practice s and adherence to nutritional recommendations were assessed , and anthropometric measurements were taken . Day-long dietary intake was evaluated on a sub sample of children . Doctors in the intervention group had better knowledge of child nutrition and improved assessment and counseling practice s. Maternal recall of recommendations was higher in the intervention than in the control group , as was satisfaction with the consultation . Reported use of recommended foods was also increased . Daily fat intake was higher in the intervention than in the control group ; mean daily intakes of energy and zinc also tended to improve . Children 12 mo of age or older had improved weight gain and a positive but nonsignificant improvement in length . Nutrition-counseling training improved doctors ' performances , maternal practice s and the diets and weight gain of children . The r and omized design with blind outcome evaluation strongly supports a causal link . These results should be replicated in other setting Complementary feeding practice s are often inadequate in developing countries , result ing in a significant nutritional decline between 6 and 18 mo of age . We assessed the effectiveness of an educational intervention to promote adequate complementary feeding practice s that would be feasible to sustain with existing re sources . The study was a cluster r and omized controlled trial in communities in the state of Haryana in India . We developed the intervention through formative research . Eight communities were pair matched on their baseline characteristics ; one of each pair was r and omly assigned to receive the intervention and the other to no specific feeding intervention . Health and nutrition workers in the intervention communities were trained to counsel on locally developed feeding recommendations . Newborns were enrolled in all of the communities ( 552 in the intervention and 473 in the control ) and followed up every 3 mo to the age of 18 mo . The main outcome measures were weights and lengths at 6 , 9 , 12 , and 18 mo and complementary feeding practice s at 9 and 18 mo . All analyses were by intent to treat . In the overall analyses , there was a small but significant effect on length gain in the intervention group ( difference in means 0.32 cm , 95 % CI , 0.03 , 0.61 ) . The effect was greater in the subgroup of male infants ( difference in mean length gain 0.51 cm , 95 % CI 0.03 , 0.98 ) . Weight gain was not affected . Energy intakes from complementary foods overall were significantly higher in the intervention group children at 9 mo ( mean + /- SD : 1556 + /- 1109 vs. 1025 + /- 866 kJ ; P < 0.001 ) and 18 mo ( 3807 + /- 1527 vs. 2577 + /- 1058 kJ ; P < 0.001 ) . Improving complementary feeding practice s through existing services is feasible but the effect on physical growth is limited . Factors that limit physical growth in such setting s must be better understood to plan more effective nutrition programs Physician behavior and caregiver retention of nutrition advice were examined as potential mediating factors in the success of a nutrition counseling efficacy trial in Pelotas , Brazil , which reduced growth faltering in children 12 - 24 mo old . After pair-matching on socioeconomic status and nutrition indicators , municipal health centers were r and omly assigned to an intervention group , in which physicians were trained with an IMCI-derived ( Integrated Management of Childhood Illness ) nutrition counseling protocol , or to a control group , without continuing education in nutrition . In a sub study of the larger trial , direct observation of consultations , followed by home interviews with mothers , provided data on physician counseling behavior and mothers ' retention of nutrition advice . Trained providers were more likely to engage in nutrition counseling ( P < 0.013 ) and to deliver more extensive advice ( P < 0.02 ) . They also used communication skills design ed to improve rapport and ensure that mothers understood the advice ( P < 0.01 ) . Mothers who received advice from trained providers had high rates of recalling the messages on specific foods ( 95 vs.27 % ; P < 0.01 ) and feeding practice and food preparation recommendations ( 90 vs. 20 % ; P < 0.01 ) , whereas the proportions of the messages recalled on breast-feeding ( 60 % vs. 30 % ) did not differ significantly ( P < 0.20 ) . The training course contained several elements that may explain why intervention group mothers were better able to recall nutrition advice . These include locally appropriate messages , tools for assessing individual problems , and counseling skills Background Underst and ing how we can prevent childhood obesity in scalable and sustainable ways is imperative . Early RCT interventions focused on the first two years of life have shown promise however , differences in Body Mass Index between intervention and control groups diminish once the interventions cease . Innovative and cost-effective strategies seeking to continue to support parents to engender appropriate energy balance behaviours in young children need to be explored . Methods / Design The Infant Feeding Activity and Nutrition Trial ( InFANT ) Extend Program builds on the early outcomes of the Melbourne InFANT Program . This cluster r and omized controlled trial will test the efficacy of an extended ( 33 versus 15 month ) and enhanced ( use of web-based material s , and Facebook ® engagement ) , version of the original Melbourne InFANT Program intervention in a new cohort . Outcomes at 36 months of age will be compared against the control group . Discussion This trial will provide important information regarding capacity and opportunities to maximize early childhood intervention effectiveness over the first three years of life . This study continues to build the evidence base regarding the design of cost-effective , scalable interventions to promote protective energy balance behaviors in early childhood , and in turn , promote improved child weight and health across the life course . Trial registration ACTRN12611000386932 . Registered 13 April 2011 OBJECTIVE Inappropriate complementary feeding is one of the major causes of malnutrition in young children in developing countries . We developed an educational intervention , delivered by local health-care providers , aim ed at improving complementary feeding practice s and child nutrition . DESIGN Eight townships in Laishui , a rural area in China , were r and omly assigned to the educational intervention or control group . A total of 599 healthy infants were enrolled at age 2 - 4 months and followed up until 1 year of age . In the intervention group , educational messages and enhanced home-prepared recipes were disseminated to caregivers through group trainings and home visits . Question naire surveys and anthropometric measurements were taken at baseline and ages 6 , 9 and 12 months . Analysis was by intention to treat . RESULTS It was found that food diversity , meal frequency and hygiene practice s were improved in the intervention group . Infants in the intervention group gained 0.22 kg more weight ( 95 % CI 0.003 , 0.45 kg , P = 0.047 ) and gained 0.66 cm more length ( 95 % CI 0.03 , 1.29 cm , P = 0.04 ) than did controls over the study period . CONCLUSIONS Findings from the study suggest that an educational intervention delivered through local health-care providers can lead to substantial behavioural changes of caregivers and improve infant growth In order to teach suitable feeding and hygiene practice s to a group of r and omly selected Qashqa'i tribe families with 406 children aged 0 - 59 months , a culturally appropriate community-based education intervention approach was used . To assess the impact of the intervention on the study group , another group of families with 405 children were r and omly selected to serve as the controls . At the beginning of the intervention programme both groups of children had access to a similar diet , consisting of cereals , beans , oil , sugar , milk and yoghurt . Baseline data , age , gender , weight , height and mean arm circumference ( MAC ) , were obtained before the intervention . Using Hubley 's behavioural change model , the components of which deal with beliefs , attitudes , subjective norms and enabling factors , the research team studied the behaviour of the family members and tried to change their nutritional behaviour . This was achieved by design ing a suitable education programme to be carried out for 12 months . During the programme , families were instructed to follow different methods of food preparation and cooking practice s. The final data were collected 3 months after the end of the intervention programme . The results indicated that the children in the study group gained : 1.16 ( sd 1.2 ) kg body weight , 0.033 ( sd 0.05 ) m in height , 0.0067 ( sd 0.015 ) m in MAC , 0.8 ( sd 1 ) in weight-for-age Z-score , 0.97 ( sd 1.7 ) in height-for-age Z-score and 0.28 ( sd 1.8 ) in weight-for-height Z-score by the end of the study . The corresponding values for the control group were 0.42 ( sd 1.0 ) , 0.0167 ( sd 0.047 ) , 0.0017 ( sd 0.012 ) , 0.35 ( sd 1.1 ) , 0.56 ( sd 1.5 ) and 0.014 ( sd 1.6 ) respectively and the differences were statistically significant ( P<0.05 ) . These findings suggest that educational interventions involving parents and /or other family members who might play a role in the care behaviour and care re sources are important in feeding the children energy- and protein-enriched , hygienic , simple and cheap foods . Such practice s could improve child growth even under conditions of poverty Background : Childhood undernutrition is a major public health problem in Bangladesh . Evaluating child nutrition programs is a priority . Objective : The objective of this study was to evaluate a community-based nutrition education program ( implemented from 2011 to 2013 ) aim ed at improving infant and young child feeding ( IYCF ) practice s and growth in rural Bangladesh . Methods : A cohort-based evaluation was conducted that included 2400 women ( 1200 from Karimganj , the intervention subdistrict , and 1200 from Katiadi , the control subdistrict ) enrolled at 28 - 31 wk gestation in 3 waves between January and October 2011 . Follow-up occurred at 3 , 9 , 16 , and 24 mo of offspring age . The main outcomes were exclusive breastfeeding ( EBF ) , measured at 3 mo , timing of complementary feeding ( CF ) initiation and minimum acceptable diet ( MAD ) , measured at 9 mo , and child growth [ assessed via length-for-age z score ( LAZ ) and weight-for-length z score ] , measured at all follow-ups . The main exposures were subdistrict of residence and wave of enrollment . For IYCF practice s as outcome , logistic regressions were used . Generalized estimating equations were used for child growth as outcome . Results : EBF rates at 3 mo remained unchanged between waves 1 and 3 in Karimganj ( 55.6 % compared with 57.3 % ) , but the proportion of infants receiving timely CF initiation and MAD at 9 mo increased significantly ( CF : 27.1 - 54.7 % ; MAD : 8.4 - 35.3 % ) . Mean LAZ at 24 mo remained unchanged between waves 1 and 3 in Karimganj ( -2.18 compared with -1.98 ) . Conclusions : The program was successful in improving the quality of infant diet at 9 mo and timely CF initiation , but not EBF at 3 mo or LAZ . These findings support the case for implementing simple messages in all programs aim ed at improving infant diet , especially in setting s in which supplementing overall household diet may not be feasible OBJECTIVE : The goal of this study was to evaluate outcomes of a universal intervention to promote protective feeding practice s that commenced in infancy and aim ed to prevent childhood obesity . METHODS : The NOURISH r and omized controlled trial enrolled 698 first-time mothers ( mean ± SD age : 30.1 ± 5.3 years ) with healthy term infants ( 51 % female ) aged 4.3 ± 1.0 months at baseline . Mothers were r and omly allocated to self-directed access to usual care or to attend two 6-session interactive group education modules that provided anticipatory guidance on early feeding practice s. Outcomes were assessed 6 months after completion of the second information module , 20 months from baseline and when the children were 2 years old . Maternal feeding practice s were self-reported by using vali date d question naires and study -developed items . Study -measured child height and weight were used to calculate BMI z scores . RESULTS : Retention at follow-up was 78 % . Mothers in the intervention group reported using responsive feeding more frequently on 6 of 9 subscales and 8 of 8 items ( all , P ≤ .03 ) and overall less controlling feeding practice s ( P < .001 ) . They also more frequently used feeding practice s ( 3 of 4 items ; all , P < .01 ) likely to enhance food acceptance . No statistically significant differences were noted in anthropometric outcomes ( BMI z score : P = .10 ) nor in prevalence of overweight/obesity ( control 17.9 % vs intervention 13.8 % ; P = .23 ) . CONCLUSIONS : Evaluation of NOURISH data at child age 2 years found that anticipatory guidance on complementary feeding , tailored to developmental stage , increased use by first-time mothers of “ protective ” feeding practice s that potentially support the development of healthy eating and growth patterns in young children BACKGROUND The effect of breastfeeding on growth in HIV-exposed infants is not well described . OBJECTIVE The objective was to evaluate the effect of early breastfeeding cessation on growth . DESIGN In a trial conducted in Lusaka , Zambia , HIV-infected mothers were r and omly assigned to exclusive breastfeeding for 4 mo followed by rapid weaning to replacement foods or exclusive breastfeeding for 6 mo followed by introduction of complementary foods and continued breastfeeding for a duration of the mother 's choice . Weight-for-age z score ( WAZ ) , length-for-age z score ( LAZ ) , and weight-for-length z score ( WLZ ) and the self-reported breastfeeding practice s of 593 HIV-uninfected singletons were analyzed . Generalized estimating equations were used to adjust for confounders . RESULTS WAZ scores declined precipitously between 4.5 and 15 mo . The decline was slower in the breastfed infants . At 9 , 12 , and 15 mo , mean WAZs were , respectively , -0.74 , -0.92 , and -1.06 in infants who were reportedly breastfed and were -1.07 , -1.20 , and -1.31 in the weaned infants ( P = 0.003 , 0.007 , and 0.02 , respectively ) . No differences were observed past 15 mo . Breastfeeding practice was not associated with LAZ , which declined from -0.98 to -2.24 from 1 to 24 mo . After adjustment for birth weight , maternal viral load , body mass index , education , season , and marital and socioeconomic status , not breastfeeding was associated with a 0.28 decline in WAZ between 4.5 and 15 mo ( P < 0.0001 ) . During the rainy season , not breastfeeding was associated with a larger WAZ decline ( 0.33 ) than during the dry season ( 0.22 ; P for interaction = 0.02 ) . CONCLUSIONS Early growth is compromised in uninfected children born to HIV-infected Zambian mothers . Continued breastfeeding partially mitigates this effect through 15 mo . Nutritional interventions to complement breastfeeding after 6 mo are urgently needed . This trial was registered at clinical trials.gov as NCT00310726 Food preferences are established in early childhood and track later in life . Therefore , it is important to promote healthy feeding practice s as early as possible . A r and omized field trial was conducted with 500 mother-child pairs from a low-income area of São Leopoldo , State of Rio Gr and e do Sul , Brazil , to evaluate the impact of a nutritional intervention in the first year of life on the dietary quality of 3- to 4-y-old children . Mother-child pairs were r and omized either to intervention and control groups and dietary counseling was provided for mothers in the intervention group during 10 home visits in the course of the first year of life . These visits were carried out by fieldworkers who counseled the mothers about the Ten Steps for Healthy Feeding from Birth to Two Years of Age , based on the WHO guidelines . Dietary intake was assessed at 3 - 4 y of age for 345 children using two 24-h food recalls . Overall diet quality was determined by the Healthy Eating Index . The prevalence of poor diet in the intervention group was lower compared with the control group [ relative risk ( RR ) = 0.30 ; 95 % CI = 0.13 - 0.71 ) . The number of children who achieved the 75th percentile for the vegetable and fruit component score was higher in the intervention than in control group ( RR = 1.95 ; 95 % CI = 1.31 - 2.89 and RR = 1.49 ; 95 % CI = 1.07 - 2.07 , respectively ) . Such data provide evidence that dietary counseling for mothers during the first year of life improves the overall dietary quality of children in a low-income population IMPORTANCE Rapid infant weight gain is associated with later obesity , but interventions to prevent rapid infant growth and reduce risk for overweight status in infancy are lacking . OBJECTIVE To examine the effect of a responsive parenting ( RP ) intervention on infant weight gain between birth and 28 weeks and overweight status at age 1 year . DESIGN , SETTING , AND PARTICIPANTS The Intervention Nurses Start Infants Growing on Healthy Trajectories ( INSIGHT ) study is an ongoing r and omized clinical trial comparing an RP intervention design ed to prevent childhood obesity with a safety control . The study includes primiparous mother-newborn dyads ( n = 291 ) and was conducted at the Penn State Milton S. Hershey Medical Center , Hershey , Pennsylvania , in addition to home visits . Enrollment was initiated in January 2012 , and evaluable population analyses for this study were conducted between April 2015 and November 2015 . INTERVENTIONS At 2 weeks post partum , initial intervention material s appropriate to the assigned treatment group were mailed to the participant 's home . Research nurses conducted home visits at 3 weeks , 16 weeks , 28 weeks , and 40 weeks , and a research center visit occurred at 1 year . The Intervention Nurses Start Infants Growing on Healthy Trajectories curriculum included messages about infant feeding , sleep hygiene , active social play , emotion regulation , and growth record education . The control group received a developmentally appropriate home safety intervention also delivered by nurse home visitors . MAIN OUTCOMES AND MEASURES Conditional weight gain from birth to 28 weeks was calculated . General linear models examined intervention effect on conditional weight gain . The intervention 's effect on infant weight-for-length percentiles was tested using analysis of variance . Logistic regression compared the odds of overweight status ( weight for length ≥95th percentile ) at 1 year as a function of conditional weight gain . RESULTS Of the mothers included in the study , 246 were white ( 88 % ) , 260 were non-Hispanic ( 93 % ) , 210 were married ( 75 % ) , and 201 were working full time ( 72 % ) at time of enrollment . The mean conditional weight gain score was lower among infants in the RP group compared with the control group ( -0.18 ; 95 % CI , -0.36 to -0.001 ) , reflecting that the RP infants gained weight more slowly than control group infants ( 0.18 ; 95 % CI , 0.02 - 0.34 ) ; this effect did not differ by feeding mode ( predominantly fed breast milk or not ) . Infants in the RP group also had lower mean weight-for-length percentiles at 1 year than infants in the control group ( 57.5 % ; 95 % CI , 52.56%-62.37 % vs 64.4 % ; 95 % CI , 59.94%-69.26 % ; P = .04 ) and were less likely to be overweight at age 1 year ( 5.5 % vs 12.7 % ; P = .05 ) . CONCLUSIONS AND RELEVANCE An RP intervention is associated with reduced rapid weight gain during the first 6 months after birth and overweight status at age 1 year . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01167270 BACKGROUND Although the WHO recommends that complementary feeding in infants should begin at 6 mo of age , it often begins before this in developed countries . OBJECTIVE Our objective was to determine whether lactation consultant ( LC ) support , with educational re sources given at 4-mo postpartum , can delay the introduction of complementary foods until around 6 mo of age . METHODS A total of 802 mother-infant pairs were recruited from the single maternity hospital serving Dunedin , New Zeal and ( 59 % response rate ) and r and omly assigned to the following : 1 ) usual care ( control group ) ; 2 ) infant sleep education intervention ( Sleep ) ; 3 ) food , activity , and breastfeeding intervention ( FAB ) ; or 4 ) combination ( both ) intervention ( Combo ) . Certified LCs delivered 3 intervention sessions ( late pregnancy and 1-wk and 4-mo postpartum ) . The 4-mo contact used educational re sources focused on developmental readiness for complementary foods . Age when complementary foods were introduced was obtained from repeated interviews ( monthly from 3- to 27-wk postpartum ) . RESULTS A total of 49.5 % and 87.2 % of infants received complementary foods before 5 and 6 mo of age , respectively . There was evidence of group differences in the number of infants introduced to complementary foods before 5 mo ( P = 0.006 ) , with those receiving support and re sources ( FAB and Combo groups combined ; 55.6 % ) more likely to wait until at least 5 mo compared with controls ( control and Sleep groups combined ; 43.3 % ) ( OR : 1.52 ; 95 % CI : 1.08 , 2.16 ) . However , there was no evidence they were more likely to wait until 6 mo of age ( P = 0.52 ) . Higher maternal age , higher parity , and a less positive attitude toward breastfeeding were positively associated , and drinking alcohol during pregnancy was negatively associated , with later age of introduction of complementary foods . CONCLUSIONS Providing an LC and educational re sources at 4-mo postpartum to predominantly well-educated , mainly European , women can delay the introduction of complementary foods until 5 mo of age , but not until the WHO recommendation of 6 mo . This trial was registered at clinical trials.gov as NCT00892983 Background Waterborne disease is a major risk for small water supplies in rural setting s. This study was done to assess the impact of an educational intervention design ed to improve water quality and estimate the contribution of water to the incidence of diarrhoeal disease in poor rural communities in Puerto Rico a two-part study was undertaken . Methods An educational intervention was delivered to communities relying on community water supplies . This intervention consisted of student operators and administrators supervising and assisting community members who voluntarily " operate " these systems . These voluntary operators had no previous training and were principally concerned with seeing that some water was delivered . The quality of that water was not something they either understood or addressed . The impact of this intervention was measured through water sampling for st and ard bacteriological indicators and a frank pathogen . In addition , face-to-face epidemiological studies design ed to determine the base-line occurrence of diarrhoeal disease in the communities were conducted . Some 15 months after the intervention a further epidemiological study was conducted in both the intervention communities and in control communities that had not received any intervention . Results Diarrhoeal illness rates over a four week period prior to the intervention were 3.5 % . Salmonella was isolated from all of 5 distributed sample s prior to intervention and from only 2 of 12 sample s after the intervention . In the 15 months follow-up study , illness rates were lower in the intervention compared to control communities ( 2.5 % vs 3.6%% ) ( RR = 0.70 , 95%CI 0.43 , 1.15 ) , though this was not statistically significant . However , in the final Poisson regression model living in an intervention system ( RR = 0.318 ; 95%CI 0.137 - 0.739 ) and owning a dog ( RR = 0.597 , 95%CI 0.145 - 0.962 ) was negatively associated with illness . Whilst size of system ( RR = 1.006 , 95%CI 1.001 - 1.010 ) and reporting problems with sewage system ( RR = 2.973 , 95%CI 1.539 - 5.744 ) were positively associated with illness . Conclusions Educational interventions directed both at identified individuals and the community in general in small communities with poor water quality is a way of giving communities the skills and knowledge to manage their own drinking water quality . This may also have important and sustainable health benefits , though further research preferably using a r and omised control trial design is needed Abstract Optimal infant and young child feeding ( IYCF ) practice s can help ensure nutrient adequacy and support healthy growth and development . Small‐quantity lipid‐based nutrient supplements ( SQ‐LNS ) have been proposed to help fill nutrient gaps , but little is known about the impact of provision of SQ‐LNS on breastfeeding or complementary feeding practice s. In the context of four coordinated r and omized controlled nutrient supplementation trials in diverse sites in Africa , we compared IYCF practice s at infant age 18 months ( after 9–12 months of supplementation ) between those receiving and not receiving SQ‐LNS . Practice s were assessed by caregiver recall . Continued breastfeeding ranged from 74 % ( Ghana site ) to 97 % ( Burkina Faso site ) and did not differ between groups in any site ; prevalence of frequent breastfeeding also did not differ . In two sites ( Burkina Faso and Malawi ) , infants receiving SQ‐LNS were more likely to meet the World Health Organization recommendations for frequency of feeding ( percentage point differences of 12–14 % , P < 0.0001 and P = 0.005 , respectively ; the remaining two sites did not have data for this indicator ) . Most indicators of infant dietary diversity did not differ between groups in any site , but in the same two sites where frequency of feeding differed , infants receiving SQ‐LNS were less likely to have low frequency of consumption of animal‐ source foods in the previous week ( percentage point differences of 9–19 % for lowest tertile , P = .02 and P = 0.04 , respectively ) . We conclude that provision of SQ‐LNS did not negatively impact self‐reported IYCF practice s and may have positively impacted frequency of feeding OBJECTIVE : To assess whether embedding pediatric anticipatory guidance into books read to infants is an effective way to educate low-income , first-time mothers about injury-prevention and health-promotion practice s. PATIENTS AND METHODS : Primiparous women ( N = 168 ) were r and omly assigned to 1 of 3 groups : an educational-book group ; a noneducational-book group ; or a no-book group . Knowledge of anticipatory-guidance topics regarding children from birth to 12 months of age ( eg , injury prevention , parenting , nutrition ) was assessed during the third trimester of pregnancy and again when infants were ∼2 , 4 , 6 , 9 , 12 , and 18 months of age . RESULTS : Women in the educational-book group scored consistently higher on knowledge than did those in the other 2 groups . Those in the educational-book group were found to have significantly higher knowledge scores than those in both the noneducational-book group ( effect size [ ES ] : 0.3 , P < .001 ) and the no-book group ( ES : 0.3 , P < .001 ) in the longitudinal model . CONCLUSIONS : Books read by mothers to infants seem to be an effective way to provide anticipatory guidance to new mothers . However , future work is needed to determine if increased knowledge translates into safer and more developmentally appropriate parenting practice OBJECTIVES : Despite recent efforts to increase breastfeeding , young African American mothers continue to breastfeed at low rates , and commonly introduce complementary foods earlier than recommended . This study examines the effects of a community doula home visiting intervention on infant feeding practice s among young mothers . METHODS : Low-income , African American mothers ( n = 248 ) under age 22 years participated in a r and omized trial of a community doula intervention . Intervention-group mothers received services from paraprofessional doulas : specialized home visitors trained as childbirth educators and lactation counselors . Doulas provided home visits from pregnancy through 3 months postpartum , and support during childbirth . Control-group mothers received usual prenatal care . Data were obtained from medical records and maternal interviews at birth and 4 months postpartum . RESULTS : Intent-to-treat analyses showed that doula-group mothers attempted breastfeeding at a higher rate than control-group mothers ( 64 % vs 50 % ; P = .02 ) and were more likely to breastfeed longer than 6 weeks ( 29 % vs 17 % ; P = .04 ) , although few mothers still breastfed at 4 months . The intervention also impacted mothers ’ cereal/solid food introduction ( P = .008 ) : fewer doula-group mothers introduced complementary foods before 6 weeks of age ( 6 % vs 18 % ) , while more waited until at least 4 months ( 21 % vs 13 % ) compared with control-group mothers . CONCLUSIONS : Community doulas may be effective in helping young mothers meet breastfeeding and healthy feeding guidelines . The intervention ’s success may lie in the relationship that develops between doula and mother based on shared cultural background and months of prenatal home visiting , and the doula ’s presence at the birth , where she supports early breastfeeding experiences BACKGROUND Iron deficiency and poor linear growth are common in infants from deprived socioeconomic background s and may be associated with inadequate complementary feeding ( CF ) practice s. OBJECTIVE We tested the hypothesis that new CF guidelines emphasizing meat as a source of iron and zinc would improve linear growth , iron , and zinc status in infants living in poor socioeconomic circumstances in Bogota , Colombia . DESIGN A total of 85 term infants who were exclusively breastfed for ≥4 mo were r and omly assigned at 6 mo of age to a control group [ CG ( n = 43 ) ; current advice ] or intervention group ( new guidelines group [ NGG ( n = 42 ) ; with counseling to 1 ) continue breastfeeding , 2 ) offer red meat ≥3 d/wk , and 3 ) offer fruit and vegetables daily ] ) . Main outcomes were 1 ) linear growth from 6 to 12 mo of age ; 2 ) hemoglobin , hematocrit , iron [ serum ferritin ( SF ) ] , and zinc status at 12 mo of age ; and 3 ) meat intake at 12 mo of age ( by using a food-frequency question naire ) . RESULTS A total of 38 infants/group provided data at 12 mo of age . NGG infants had significantly higher red meat intake [ mean ± SD : 5.4 ± 1.8 compared with 3.5 ± 1.7 d/wk at 12 mo of age ; P < 0.001 ) , higher hemoglobin and hematocrit at 12 mo of age , and a significantly greater increase in hemoglobin ( mean ± SD change : 0.41 ± 0.8 compared with -0.13 ± 1.0 ; P = 0.01 ) and hematocrit ( 1.04 ± 2.2 compared with -0.15 ± 2.4 ; P = 0.03 ) from 6 to 12 mo of age than those in CG infants . There were no significant differences in linear growth from 6 to 12 mo of age or in SF or zinc . CONCLUSIONS The new guidelines showed efficacy with higher red meat intake and positive effects on hemoglobin and hematocrit . The intervention was acceptable and affordable for most mothers . These preliminary results suggest that the intervention merits investigation in a larger cohort with longer-term follow-up . This trial was registered at http://is rct n.org as IS RCT N57733004 Responsive complementary feeding , whereby the mother feeds her child in response to child cues of hunger state and psychomotor abilities , is a problem in some countries , and likely contributes to malnutrition . Interventions are needed to evaluate whether promoting responsive feeding would add any benefit . Using a cluster r and omized field trial , we evaluated a six-session educational programme that emphasized practice of two key behaviours , namely child self-feeding and maternal responsiveness . One hundred mothers and their 12- to 24-month-olds attended the sessions as part of village clusters r and omly assigned to the intervention group . A similar number of controls received sessions on foods to feed and nutritional disorders . Outcomes assessed at pre-test , 2-week post-intervention and again 5-months post-intervention included weight , mouthfuls of food taken , self-feeding and maternal responsiveness . Research assistants , blind to group assignment , observed and coded mother and child behaviours during the midday meal . Secondary measures included foods fed and feeding messages recalled . Analysis was based on intention to treat and accounted for clustering . Only 10 % of each group was lost to follow-up . Weight ( d = 0.28 ) , weight gain ( d = 0.48 ) and child self-feeding ( d = 0.30 ) were significantly higher in the responsive feeding group . Mouthfuls of food eaten and maternal responsiveness were not significantly increased by the intervention . Mothers in the intervention gave their children more vegetables , and spontaneously recalled more feeding messages at the 5-month follow-up . These results provide evidence that self-feeding and weight gain can improve by targeting specific behaviours , while maternal responsiveness may require more intensive strategies Poor infant and young child feeding ( IYCF ) practice s are major determinants of chronic malnutrition . The main objective of this study was to assess the impact of a nutrition education ( NE ) programme aim ed at promoting improved IYCF behaviours in combination with an agriculture intervention on children ’s dietary diversity and nutritional status . From 2012 to 2014 , a cluster r and omised trial was rolled out in Cambodia in the context of an agriculture and nutrition project of the FAO of the UN . The cross-sectional baseline study was carried out in sixteen pre-selected communes in 2012 . Restricted r and omisation allotted the communes to either intervention ( NE and agriculture intervention ) or comparison arms ( agriculture intervention only ) . The impact survey was conducted as a census in all FAO project villages in 2014 . Caregivers of children aged 0–23 months were interviewed using st and ardised questions on socio-economic status and dietary diversity ( 24-h recall ) . Anthropometric measurements were taken . A difference-in-differences model was applied . The sample comprised 743 households with children ≥6 months of age at baseline and 921 at impact . After 1 year of NE , 69 % of the intervention households reported to have participated in the NE . Estimated mean child dietary diversity was significantly different at impact between comparison and intervention ( 3·6 and 3·9 , respectively ) . In particular , the consumption of pro-vitamin A-rich foods and other fruits and vegetables increased . No treatment effects on height-for-age Z-scores could be shown . NE led to improvements in children ’s diets . For effects on growth , it is assumed that longer NE activities are required to achieve sustainable behaviour change of age-appropriate infant feeding Background Unhealthy infant feeding practice s , such as a combination of formula feeding and early introduction of solids may lead to rapid or excessive weight gain in early infancy . Adolescent mothers ’ feeding behaviors are most directly related to infant weight gain in the first year of life . Compared to adult mothers , adolescent mothers are less knowledgeable , less responsive , more controlling , and less skilled in infant feeding , which interferes with infants ’ healthy growth . The Tools for Teen Moms trial aims to compare the effect of a social media intervention for low-income adolescent , first-time mothers of infants 2 months of age or younger , versus st and ard care on infant weight , maternal responsiveness , and feeding style and practice s. The intervention is conducted during the infant ’s first four months of life to promote healthy transition to solids during their first year . Tools for Teen Moms is an intervention delivered via a social media platform that actively engages and coaches low-income adolescent mothers in infant-centered feeding to reduce rapid/excessive infant weight gain in the first six months of life . Methods / Design We describe our study protocol for a r and omized control trial with an anticipated sample of 100 low-income African- American and Caucasian adolescent , first – time mothers of infants . Participants are recruited through Maternal-Infant Health Programs in four counties in Michigan , USA . Participants are r and omly assigned to the intervention or the control group . The intervention provides infant feeding information to mothers via a web-based application , and includes daily behavioral challenges , text message reminders , discussion forums , and website information as a comprehensive social media strategy over 6 weeks . Participants continue to receive usual care during the intervention . Main maternal outcomes include : ( a ) maternal responsiveness , ( b ) feeding style , and ( c ) feeding practice s. The primary infant outcome is infant weight . Data collection occurs at baseline , and when the baby is 3 and 6 months old . Discussion Expected outcomes will address the effectiveness of the social media intervention in helping teen mothers develop healthy infant feeding practice s that contribute to reducing the risk of early onset childhood obesity . Trial registration Clinical Trials . Gov NCT02244424 , June 24 , BACKGROUND The American Academy of Pediatrics , the Special Supplemental Nutrition Program for Women , Infants , and Children ( WIC ) , and the World Health Organization recommend that infants receive only breast milk or formula for the first 4 to 6 months of life , followed by the introduction of complementary foods . Despite these recommendations , many infants , particularly those with adolescent mothers , receive solid foods ( often cereal mixed with formula in a bottle ) and liquids other than formula or breast milk in the first few weeks of life . Decisions on early feeding are often guided by gr and mothers and influenced by beliefs that infants need complementary food to counteract signals of hunger , reduce crying , and sleep through the night . OBJECTIVE This investigation evaluated the efficacy of an intervention to delay the early introduction of complementary feeding among first-time , black , adolescent mothers living in multigenerational households . The intervention focused on reducing the cultural barriers to the acceptance of the recommendations of the American Academy of Pediatrics , WIC , and World Health Organization on complementary feeding by highlighting 3 topics : 1 ) recognition of infants ' cues ; 2 ) nonfood strategies for managing infant behavior ; and 3 ) mother-gr and mother negotiation strategies . The intervention was delivered through a mentorship model in which a videotape made by an advisory group of black adolescent mothers was incorporated into a home-visiting program and evaluated through a r and omized , controlled trial . METHODS One hundred eighty-one first-time , low-income , black mothers < 18 years old , living in multigenerational households were recruited from 3 urban hospitals . Infants were born at term , with birth weight appropriate for gestational age and no congenital problems . Shortly after delivery , mothers and gr and mothers completed a baseline assessment and mothers were r and omized into an intervention or control group . Intervention group mothers received home visitation every other week for 1 year . At 3 months , a subset of 121 adolescent mothers reported on their infant 's intake through a food frequency question naire . Mothers who fed their infant only breast milk , formula , or water were classified as optimal feeders . Mothers who provided complementary foods other than breast milk , formula , or water were classified as less optimal feeders . RESULTS Sixty-one percent of the infants received complementary foods before 3 months old . Multivariate hierarchical logistic regression was used to evaluate the determinants of being in the optimal versus less optimal feeders group . After controlling for infant age and family income , mothers of infants in the optimal feeders group were more likely to report accurate messages from WIC regarding the timing of complementary food and nearly 4 times more likely to be in the intervention group . The most common complementary food was cereal mixed with formula in the bottle . CONCLUSIONS The success of this relatively brief intervention demonstrates the importance of using ecological theory and ethnographic research to design interventions that enable participants to alter their behavior in the face of contradictory cultural norms . The intervention focused on interpreting infants ' cues , nonfood methods of managing infant behavior , and mother-gr and mother negotiations . It was delivered through methods that were familiar and acceptable to adolescent mothers-a mentorship model incorporating home visits and videotape . The skill-oriented aspects of the intervention delivered in a culturally sensitive context may have enabled the young mothers to follow the guidelines that they received from WIC and from their pediatricians . Strategies , such as those used in this intervention , may be effective in promoting other caregiving recommendations , thereby enabling providers to meet the increasing dem and s from parents for advice regarding children 's early growth and development Child stunting and anemia are intractable public health problems in developing countries and have profound short- and long-term consequences . The Sanitation Hygiene Infant Nutrition Efficacy ( SHINE ) trial is motivated by the premise that environmental enteric dysfunction ( EED ) is a major underlying cause of both stunting and anemia , that chronic inflammation is the central characteristic of EED mediating these adverse effects , and that EED is primarily caused by high fecal ingestion due to living in conditions of poor water , sanitation , and hygiene ( WASH ) . SHINE is a proof-of-concept , 2 × 2 factorial , cluster-r and omized , community-based trial in 2 rural districts of Zimbabwe that will test the independent and combined effects of protecting babies from fecal ingestion ( factor 1 , operationalized through a WASH intervention ) and optimizing nutritional adequacy of infant diet ( factor 2 , operationalized through an infant and young child feeding [ IYCF ] intervention ) on length and hemoglobin at 18 months of age . Within SHINE we will measure 2 causal pathways . The program impact pathway comprises the series of processes and behaviors linking implementation of the interventions with the 2 child health primary outcomes ; it will be modeled using measures of fidelity of intervention delivery and household uptake of promoted behaviors and practice s. We will also measure a range of household and individual characteristics , social interactions , and maternal capabilities for childcare , which we hypothesize will explain heterogeneity along these pathways . The biomedical pathway comprises the infant biologic responses to the WASH and IYCF interventions that ultimately result in attained stature and hemoglobin concentration at 18 months of age ; it will be eluci date d by measuring biomarkers of intestinal structure and function ( inflammation , regeneration , absorption , and permeability ) ; microbial translocation ; systemic inflammation ; and hormonal determinants of growth and anemia among a subgroup of infants enrolled in an EED sub study . This article describes the rationale , design , and methods underlying the SHINE trial . Clinical Trials Registration . NCT01824940 Inadequate feeding and care may contribute to high rates of stunting and underweight among children in rural families in India . This cluster-r and omized trial tested the hypothesis that teaching caregivers appropriate complementary feeding and strategies for how to feed and play responsively through home-visits would increase children 's dietary intake , growth and development compared with home-visit-complementary feeding education alone or routine care . Sixty villages in And hra Pradesh were r and omized into three groups of 20 villages with 200 mother-infant dyads in each group . The control group ( CG ) received routine Integrated Child Development Services ( ICDS ) ; the complementary feeding group ( CFG ) received the ICDS plus the World Health Organization recommendations on breastfeeding and complementary foods ; and the responsive complementary feeding and play group ( RCF&PG ) received the same intervention as the CFG plus skills for responsive feeding and psychosocial stimulation . Both intervention groups received bi-weekly visits by trained village women . The groups did not differ at 3 months on socioeconomic status , maternal and child nutritional indices , and maternal depression . After controlling for potential confounding factors using the mixed models approach , the 12-month intervention to the CFG and RCF&PG significantly ( P < 0.05 ) increased median intakes of energy , protein , Vitamin A , calcium ( CFG ) , iron and zinc , reduced stunting [ 0.19 , confidence interval ( CI ) : 0.0 - 0.4 ] in the CFG ( but not RCF&PG ) and increased ( P < 0.01 ) Bayley Mental Development scores ( mean = 3.1 , CI : 0.8 - 5.3 ) in the RCF&PG ( but not CFG ) compared with CG . Community-based educational interventions can improve dietary intake , length ( CFG ) and mental development ( RCF&PG ) for children under 2 years in food-secure rural Indian families Malnutrition is common among children aged 6–24 months in developing countries . It increases the risk of mortality . Interventions to improve infant-feeding hold the promise of reducing malnutrition among these children . A study in Brazil has shown the success of training in communication and counselling skills among health workers in improving the nutritional status of young children . Questions were raised whether the method used in the study in Brazil would also be effective when applied in other countries . The aim of the present study was to reduce growth faltering in young children through proper nutrition-promotion techniques . The objective of the study was to determine the efficacy of training health workers in nutrition counselling in enhancing their communication skills and performance , improving feeding practice s , and reducing growth faltering in children aged 6–24 months . A cluster-r and omized controlled trial was carried out . The method used in this study was a replica of the method in a similar study in Pelotas , Brazil . Forty health centres were paired , and one centre of each pair was r and omly allocated to the intervention group , and the other to the control group . The Integrated Management of Childhood Illness ( IMCI ) module—‘Counsel the mother'—was used for training health workers in the health centres in the intervention group . Data from 36 paired health centres and 375 mothers and their children aged 6–24 months recruited from these health centres following consultation with health workers were included in analysis . Independent observers , masked to the intervention status , examined the performance of health workers within the first month after training . Mother-child pairs were visited at home within two weeks , 45 days , and 180 days after recruitment . Information was recorded on the feeding practice s , recall of the recommendations of health workers , and sociodemographic variables at these home-visits . Weight and length of the child were measured at each contact . The communication skills and consultation performance of health workers were significantly better in the intervention group than in the control group . The mothers ' recall of the recommendation of health workers and reported infant-feeding practice s were also significantly better in the intervention group than in the control group , even 180 days after the recruitment consultation . Growth faltering was less in the intervention group , with the largest effect observed among children in the age-group of 12 + months . These results indicate that training in IMCI feeding counselling can enhance the communication skills and performance of health workers . Improved feeding practice s of counselled mothers can , in turn , reduce growth faltering in their children More than 20 % of US children between ages 2 and 5 years are overweight suggesting efforts to prevent obesity must begin earlier . This study tested the independent and combined effects of two behavioral interventions delivered to parents , design ed to promote healthy infant growth in the first year . Mother-newborn dyads intending to breastfeed were recruited from a maternity ward . With a 2 × 2 design , 160 dyads were r and omized into one of four treatment cells to receive both , one , or no interventions delivered at two nurse home visits . The first intervention ( " Soothe/Sleep " ) instructed parents on discriminating between hunger and other sources of infant distress . Soothing strategies were taught to minimize feeding for non-hunger-related fussiness and to prolong sleep duration , particularly at night . The second intervention ( " Introduction of Solids " ) taught parents about hunger and satiety cues , the timing for the introduction of solid foods , and how to overcome infants ' initial rejection of healthy foods through repeated exposure . A total of 110 mother-infant dyads completed the year-long study . At 1 year , infants who received both interventions had lower weight-for-length percentiles ( P = 0.009 ) . Participants receiving both interventions had a mean weight-for-length in the 33rd percentile ; in contrast , those in other study groups were higher first intervention only--50th percentile ; second intervention only--56th percentile ; control group--50th percentile).This suggests that multicomponent behavioral interventions may have potential for long-term obesity prevention ( Clinical Trials.gov number , NCT00359242 ) Inappropriate complementary feeding practice s have led to , in part , significant disparities in growth and nutritional status between rural and urban children in China . A cluster-r and omised , controlled trial was implemented in Laishui , China to assess the effectiveness of an educational intervention on caregivers ' feeding practice s and children 's growth . Eight townships were r and omly assigned to the intervention or control . Five hundred ninety-nine healthy infants were enrolled at 2 - 4 months old , and were followed up at ages 6 , 9 , 12 , 15 and 18 months . The intervention group received information on enhanced home-prepared recipes and food preparation and hygiene through group training , counselling and home visit . Key outcomes were children 's physical growth , caregivers ' knowledge and behaviours on complementary feeding , and the infant and child feeding index ( ICFI ) . Analysis was by intention to treat . The intervention group achieved better knowledge and practice s related to complementary feeding , and significantly higher ICFI scores at each follow-up point . Children in the intervention group achieved higher z-scores for weight-for-age ( WAZ ) and weight-for-height ( WHZ ) than the control ( 0.18 vs. 0.01 and 0.49 vs. 0.19 , respectively ) at 18 months old , and were less likely to have stunted growth ( odds ratio = 0.71 , 95 % confidence interval : 0.53 - 0.94 ) . Mixed model showed that the intervention group achieved significantly better linear growth over time , including WAZ ( P = 0.016 ) , WHZ ( P = 0.030 ) and HAZ ( P = 0.078 ) . These results indicated that an educational intervention delivered through local health services can enhance caregivers ' knowledge and practice s of complementary feeding and ultimately improve children 's growth We developed a program intended to modify maternal attitudes towards feeding in order to delay the introduction of solids to infants until they are 2 months of age . The program was provided by nurses using an individualized , educational approach . To evaluate its efficacy , a r and omized trial design was used . The results in the 2 groups were comparable . The educational trial 's lack of success when compared to others and the reasons for this are discussed Objective . Theory use may enhance effectiveness of behavioral interventions , yet critics question whether theory-based interventions have been sufficiently scrutinized . This study applied a framework to evaluate theory use in physical activity interventions for breast cancer survivors . The aims were to ( 1 ) evaluate theory application intensity and ( 2 ) assess the association between extensiveness of theory use and intervention effectiveness . Methods . Studies were previously identified through a systematic search , including only r and omized controlled trials published from 2005 to 2013 , that addressed physical activity behavior change and studied survivors who were < 5 years posttreatment . Eight theory items from Michie and Prestwich ’s coding framework were selected to calculate theory intensity scores . Studies were classified into three subgroups based on extensiveness of theory use ( Level 1 = sparse ; Level 2 = moderate ; and Level 3 = extensive ) . Results . Fourteen r and omized controlled trials met search criteria . Most trials used the transtheoretical model ( n = 5 ) or social cognitive theory ( n = 3 ) . For extensiveness of theory use , 5 studies were classified as Level 1 , 4 as Level 2 , and 5 as Level 3 . Studies in the extensive group ( Level 3 ) had the largest overall effect size ( g = 0.76 ) . Effects were more modest in Level 1 and 2 groups with overall effect sizes of g = 0.28 and g = 0.36 , respectively . Conclusions . Theory use is often viewed as essential to behavior change , but theory application varies widely . In this study , there was some evidence to suggest that extensiveness of theory use enhanced intervention effectiveness . However , there is more to learn about how theory can improve interventions for breast cancer survivors The period from conception to 24 months of age is a crucial window for nutrition interventions . Personalized maternal counseling may improve childbirth outcomes , growth , and health . We assessed the effectiveness of facility-based personalized maternal nutrition counseling ( from pregnancy to 18 months after birth ) in improving child growth and health in rural Burkina Faso . We conducted a paired cluster r and omized controlled trial in a rural district of Burkina Faso with 12 primary health centers ( clusters ) . Healthcare providers in the intervention centers received patient-centered communication and nutrition counseling training . Pregnant women in the third trimester living in the center catchment areas and intending to stay for the next 2 years were prospect ively included . We followed 2253 mother-child pairs quarterly until the child was aged 18 months . Women were interviewed about counseling experiences , dietary practice s during pregnancy , and their child ’s feeding practice s and morbidity history . Anthropometric measurements were taken at each visit using st and ardized methods . The primary outcomes were the cumulative incidence of wasting , and changes in child weight-for-height z-score ( WHZ ) . Secondary outcomes were the women ’s prenatal dietary practice s , early breastfeeding practice s , exclusive breastfeeding , timely introduction of complementary food , child ’s feeding frequency and dietary diversity , children ’s mean birth weight , endpoint prevalence of stunting , and cumulative incidence of diarrhea , fever , and acute respiratory infection . All analyses were by intention-to-treat using mixed effects models . The intervention and control arms each included six health centers . Mothers in the intervention arm had a significantly higher exposure to counseling with 11.2 % for breastfeeding techniques to 75.7 % for counseling on exclusive breastfeeding . Mothers of infants below 6 months of age in the intervention arm were more likely to exclusively breastfeed ( 54.3 % vs 42.3 % ; Difference of Proportion ( DP ) 12.8 % ; 95 % CI : 2.1 , 23.6 ; p = 0.020 ) as compared to the control arm . Between 6 and 18 months of age , more children in the intervention arm benefited from the required feeding frequency ( 68.8 % vs 53.4 % ; DP 14.1 % ; 95 % CI : 9.0 , 19.2 ; p<0.001 ) and a larger proportion had a minimum dietary diversity ( 28.6 % vs 22.0 % ; DP 5.9 % ; 95 % CI : 2.7 , 9.2 ; p<0.001 ) . Birth weight of newborns in the intervention arm was on average 84.8 g ( p = 0.037 ) larger compared to the control arm . However , we found no significant differences in child anthropometry or morbidity between study arms . Facility-based personalized maternal nutrition counseling was associated with an improved prenatal dietary practice s , Infant and Young Child Feeding practice s , and child birth weight . Complementary strategies are warranted to obtain meaningful impact on child growth and morbidity . This includes strategies to ensure good coverage of facility-based services and effective nutrition/care practice s in early childhood OBJECTIVE : To assess the impact of dietary counseling given to mothers during the first year of infants ’ lives on food consumption , nutritional status , and lipid profile of the children up to 7 to 8 years old . METHODS : The r and omized trial was conducted with 500 mothers who gave birth to full-term infants with birth weight ≥2500 g between October 2001 and June 2002 in São Leopoldo , Brazil . Mothers were r and omly assigned to intervention ( n = 200 ) and control groups ( n = 300 ) and those in the intervention group received counseling on breastfeeding and complementary feeding by 12 fieldworkers on 10 home visits during the first year of children ’s lives . Blinded fieldworkers assessed dietary and anthropometric data at 12 to 16 months , 3 to 4 years , and 7 to 8 years and lipid profiles at 3 to 4 years and 7 to 8 years old . The lipid profile was the primary outcome . RESULTS : Of the 500 recruited children , 397 underwent the 12- to 16-month , 354 the 3- to 4-year , and 315 the 7- to 8-year assessment . The energy-dense foods intake was significantly lower in the intervention group at 12 to 16 months and 3 to 4 years old . At 3 to 4 years , serum lipid levels did not differ between groups . At 7 to 8 years , high-density lipoprotein levels were 0.11 mmol/L higher ( 0.00 to 0.20 ) , and triglycerides concentration was 0.13 mmol/L lower ( −0.25 to −0.01 ) in intervention children but only among the girls . Overweight/obesity rates did not differ between groups . CONCLUSIONS : Dietary counseling for mothers during infancy decreased the energy-dense foods consumption and improved lipid profile OBJECTIVES In a community r and omized trial , we aim ed to promote exclusive breastfeeding and appropriate complementary feeding practice s in under-twos to ascertain the feasibility of using available channels for nutrition counselling , their relative performance and the relationship between intensity of counselling and behaviour change . We also assessed whether using multiple opportunities to impart nutrition education adversely affected routine activities . METHODS We conducted a community r and omized , controlled effectiveness trial in rural Haryana , India , with four intervention and four control communities . We trained health and nutrition workers in the intervention communities to counsel mothers at multiple contacts on breastfeeding exclusively for 6 months and on appropriate complementary feeding practice s thereafter . The intervention was not just training health and nutrition workers in counselling but included community and health worker mobilization . FINDINGS In the intervention group , about 32 % of caregivers were counselled by traditional birth attendants at birth . The most frequent sources of counselling from birth to 3 months were immunization sessions ( 45.1 % ) and home visits ( 32.1 % ) , followed closely by weighing sessions ( 25.5 % ) ; from 7 to 12 months , home visits ( 42.6 % ) became more important than the other two . An increase in the number of channels through which caregivers were counselled was positively associated with exclusive breastfeeding prevalence at 3 months ( p = 0.002 ) , consumption of milk/cereal gruel or mix use at 9 months ( p = 0.004 ) and 18 months ( p = 0.003 ) , undiluted milk at 9 months ( p<0.0001 ) and 24 hour non-breast-milk energy intakes at 18 months ( p = 0.023 ) , after controlling for potential confounding factors . Intervention areas , compared with the control , had higher coverage for vitamin A ( 45 % vs. 11.5 % ) and iron folic acid ( 45 % vs. 0.4 % ) supplementation . CONCLUSIONS Using multiple available opportunities and workers for counselling caregivers was feasible , result ed in high coverage and impact , and instead of disrupting ongoing services , result ed in their improvement Background Nutrition in the first 1,000 days of life ( during pregnancy and the first two years ) is critical for child growth and survival . Poor maternal , infant and young child nutrition ( MIYCN ) practice s are widely documented in Kenya , with potential detrimental effects on child growth and survival . This is particularly a problem in slums , where most urban residents live . For example , exclusive breastfeeding for the first six months is only about two per cent . Innovative strategies to reach slum residents are therefore needed . Strategies like the Baby Friendly Hospital Initiative have proven effective in some setting s but their effectiveness in re source -limited setting s , including slums where many women do not deliver in hospital , is question able . We propose to test the effectiveness of a home-based intervention on infant feeding practice s , nutrition and health outcomes of infants born in two slums in Nairobi , Kenya . Methods / Design The study , employing a cluster-r and omised study design , will be conducted in two slums in Nairobi : Korogocho and Viw and ani where 14 community units ( defined by the Government ’s health care system ) will form the unit of r and omization . A total of 780 pregnant women and their respective child will be recruited into the study . The mother-child pair will be followed up until the child is one year old . Recruitment will last approximately one year and three months from September 2012 to December 2013 . The mothers will receive regular , personalised , home-based counselling by trained Community Health Workers on MIYCN . Regular assessment of knowledge , attitudes and practice s on MIYCN will be done , coupled with assessment s of nutritional status of the mother-child pairs and diarrhea morbidity for the children . Statistical methods will include analysis of covariance and multinomial logistic regression . Additionally , cost-effectiveness analysis will be done . The study is funded by the Wellcome Trust and will run from March 2012 to February 2015 . Discussion Interventions aim ed at promoting optimal breastfeeding and complementary feeding practice s are considered to have high impact and could prevent a fifth of the under-five deaths in countries with high mortality rates . This study will inform policy and practice in Kenya and similar setting s regarding delivery mechanisms for such high-impact interventions , particularly among urban poor population s . Trial registration IS RCT Objective . A pediatric office-based intervention was implemented following a r and omized , controlled design , aim ed at improving child feeding practice s and growth patterns and ultimately reducing risk for overweight and obesity later in life . Methods . Four clinics ( 232 infants ) were r and omized to control or intervention ( I ) , the latter delivered by health care provider at each of 7–9 well-baby visits over 2 years , using a previously developed program ( Growing Leaps and Bounds ) that included verbal , visual , and text advice and information for parents . Results . The I group offered significantly less soda ( p = 0.006 ) , sweetened tea ( p = 0.01 ) , punch ( p = 0.02 ) and /or cow 's milk ( p = 0.001 ) to infants and delayed the introduction of drink/food other than breast milk ( p < 0.05 ) . Parents in the I group had a higher perceived parental monitoring ( p = 0.05 ) and restriction ( p = 0.01 ) on infant feeding . While the I group exhibited at baseline more adverse socioeconomic indicators than the control group , growth trajectory or body size indices did not significantly differ between groups . Conclusions . Education provided by health care providers in addition to follow-up monthly phone calls may help modify parental behaviors related to child feeding and increase parental sense of responsibility toward child eating behaviors Background Strategies to improve infant and young child nutrition in low- and middle- income countries need to be implemented at scale . We context ualised and packaged successful strategies into a feasible intervention for implementation in rural Tanzania . Opportunities that can optimise delivery of the intervention and encourage behaviour change include mothers willingness to modifying practice s ; support of family members ; seasonal availability and accessibility of foods ; established set-up of village peers and functioning health system . The primary objective of the study is to evaluate the effectiveness of a nutrition education package in improving feeding practice s , dietary adequacy and growth as compared to routine health education . Methods / Design A parallel cluster r and omised controlled trial will be conducted in rural central Tanzania in 9 intervention and 9 control villages . The control group will receive routine health education offered monthly by health staff at health facilities . The intervention group will receive a nutrition education package in addition to the routine health education . The education package is comprised of four components : 1 ) education and counselling of mothers , 2 ) training community-based nutrition counsellors and monthly home visits , 3 ) sensitisation meetings with health staff and family members , and 4 ) supervision of community-based nutrition counsellors . The duration of the intervention is 9 months and infants will be recruited at 6 months of age . Primary outcome ( linear growth as length-for-age Z-scores ) and secondary outcomes ( changes in weight-for-length Z-scores ; mean intake of energy , fat , iron and zinc from complementary foods ; proportion of children consuming 4 or more food groups and recommended number of semi-solid/soft meals and snacks per day ; maternal level of knowledge and performance of recommended practice s ) will be assessed at baseline and ages 9 , 12 and 15 months . Process evaluation will document reach , dose and fidelity of the intervention and context at 8 and 15 months . Discussion Results of the trial will provide evidence of the effectiveness of the nutrition education package in community setting s of rural Tanzania . They will provide recommendations for strengthening the nutrition component of health education in child health services . Trial registration Clinical Trials.gov Identifier : NCT02249754 , September 25 , 2014 Background Obesity is a major problem in the United States , particularly among socio-economically disadvantaged Latino and Black children . Effective interventions that can be disseminated to large numbers of at-risk children and their families are needed . The goals of the Early Childhood Obesity Prevention Program ( ECHO ) are to examine the 12-month efficacy of a primary obesity prevention program targeting the first year of life that is delivered by home visitors and that engages mothers as agents of change to modify their own behavior and their infant ’s behavior through education and skill-building around nutrition , physical activity , and wellness , and then “ echoes ” her training with linkages to neighborhood programs and re sources . Methods / Design Six family centers located in low-income neighborhoods in Hartford , CT were r and omized into control and intervention neighborhoods . Fifty-seven mothers were recruited either prenatally or shortly after delivery into the Nurturing Families Network home visitation program ; 27 lived in a control neighborhood and received the st and ard home visitation program and 30 lived in an intervention neighborhood and received both the st and ard home visitation program and the ECHO intervention . The intervention increases maternal skills in goal - setting , stimulus control and problem-solving , engages family members to support changes , links mothers to neighborhood re sources and is embedded in the st and ard home visitation program . ECHO targets include breastfeeding , solids , juice and sugar-sweetened beverages , routines for sleep and responding to infant cues , television/screen time , and maternal diet and physical activity . We hypothesize that infants in ECHO will have been breastfed longer and exclusively , will have delayed introduction of solids and juice , have longer sleep duration , decreased television/screen time and a lower weight for length z-score at 12 months , and their mothers will have greater fruit and vegetable consumption and higher levels of physical activity . Discussion ECHO will provide important information about whether an enhanced behavior change curriculum integrated into an existing home visitation program , focused on the mother as the agent of change and linked to neighborhood re sources is effective in changing energy balance behaviors in the infant and in the mother . If effective , the intervention could be widely disseminated to prevent obesity in young children . Trial Registration Clinical Trials.gov NCT02052518 January 30 , 2014 Background Over half of the world ’s children suffer from poor nutrition , and as a consequence they experience delays in physical and mental health , and cognitive development . There is little data evaluating the effects of delivery of lipid-based , nutrition supplementation on growth and development during pregnancy and early childhood within the context of a scaled-up program . Furthermore , there is limited evidence on effects of scaled-up , home-visiting programs that focus on the promotion of child development within the context of an existing , national nutrition program . Methods / Design The MAHAY ( " smart " in Malagasy ) study uses a multi-arm r and omized-controlled trial ( RCT ) to test the effects and cost-effectiveness of combined interventions to address chronic malnutrition and poor child development . The arms of the trial are : ( T0 ) existing program with monthly growth monitoring and nutritional/hygiene education ; ( T1 ) is T0 + home visits for intensive nutrition counseling within a behavior change framework ; ( T2 ) is T1 + lipid-based supplementation ( LNS ) for children 6–18 months old ; ( T3 ) is T2 + LNS supplementation of pregnant/lactating women ; and ( T4 ) is T1 + intensive home visiting program to support child development . There are anticipated to be n = 25 communities in each arm ( n = 1250 pregnant women , n = 1250 children 0–6 months old , and n = 1250 children 6–18 months old ) . Primary outcomes include growth ( length/height-for-age z-scores ) and child development ( mental , motor and social development ) . Secondary outcomes include care-giver reported child morbidity , household food security and diet diversity , micro-nutrient status , maternal knowledge of child care and feeding practice s , and home stimulation practice s. We will estimate unadjusted and adjusted intention-to-treat effects . Study protocol s have been review ed and approved by the Malagasy Ethics Committee at the Ministry of Health in Madagascar and by the institutional review board at the University of California , Davis . This study is funded by the Strategic Impact Evaluation Fund ( SIEF ) , the World Bank Innovation Grant , the Early Learning Partnership Grant , the Japan Scaling-up for Nutrition Trustfund , and Gr and Challenges Canada . The implementation of the study is financed by Madagascar 's National Nutrition Office . Trial registration Current Controlled Trials IS RCT N14393738 . Registered June 23 , 2015 ABSTRACT This cluster-r and omized interventional trial at peri-urban setting s of Karachi was conducted to evaluate the impact of maternal educational messages regarding appropriate complementary feeding ( CF ) on the nutritional status of their infants after 30 weeks of educational interventions delivered by trained community health workers . Mothers in the intervention group received three education modules about breastfeeding ( BF ) and appropriate CF at a baseline visit and two subsequent visits 10 weeks apart . The control group received advice about BF according to national guidelines . Infants ' growth [ weight , length , and mid-upper arm-circumference ( MUAC ) , stunting , wasting , and underweight ] were measured at four time points . At the end of the study , infants in the intervention group had a higher mean weight of 350 g ( p=0.001 ) ; length of 0.66 cm ( p=0.001 ) , and MUAC of 0.46 cm ( p=0.002 ) compared to the controls ; proportionate reduction of stunting and underweight were 10 % ( 84 % vs 74 % ; ORadj 8.36 ( 5.6 - 12.42 ) and 5 % ( 25 % vs 20 % ; ORadj 0.75 ( 0.4 - 1.79 ) in the intervention compared to the control group . For relatively food-secure population s , educational interventions about appropriate CF to mothers had a direct positive impact on linear growth of their infants Background Poor feeding practice s during infancy contribute to obesity risk . As infants transition from human milk and /or formula-based diets to solid foods , these practice s interfere with infant feeding self-regulation and healthy growth patterns . Compared with other socioeconomic groups , lower-income mothers are more likely to experience difficulty feeding their infants . This may include misinterpreting feeding cues and using less-than-optimal feeding styles and practice s , such as pressuring infants during mealtimes and prematurely introducing solid food and sweetened beverages . The Healthy Babies trial aims to determine the efficacy of a community-based r and omized controlled trial of an in-home intervention with economically and educationally disadvantaged mother-infant dyads . The educational intervention is being conducted during the infant 's first 6 months of life to promote healthy transition to solids during their first year and is based on the theory of planned behavior . Methods / Design We will describe our study protocol for a multisite r and omized control trial being conducted in Colorado and Michigan with an anticipated sample of 372 economically and educationally disadvantaged African American , Hispanic , and Caucasian mothers with infants . Participants are being recruited by county community agency staff . Participants are r and omly assigned to the intervention or the control group . The intervention consists of six in-home visits by a trained paraprofessional instructor followed by three reinforcement telephone contacts when the baby is 6 , 8 , and 10 months old . Main maternal outcomes include a ) maternal responsiveness , b ) feeding style , and c ) feeding practice s. Main infant outcome is infant growth pattern . All measures occur at baseline and when the infant is 6 and 12 months old . Discussion If this project is successful , the expected outcomes will address whether the home-based early nutrition education intervention is effective in helping mothers develop healthy infant feeding practice s that contribute to improving infant health and development and reducing the risk of early-onset childhood obesity . Trial Registration Current Controlled Trials Background : Complementary feeding ( CF ) contributes to child growth and development , but few CF programs are delivered at scale . Alive & Thrive addressed this in Bangladesh through intensified interpersonal counseling ( IPC ) , mass media ( MM ) , and community mobilization ( CM ) . Objective : The objective was to evaluate the impact of providing IPC + MM + CM ( intensive ) compared with st and ard nutrition counseling + less intensive MM + CM ( nonintensive ) on CF practice s and anthropometric measurements . Methods : We used a cluster-r and omized , nonblinded evaluation with cross-sectional surveys [ n = ∼600 and 1090 children 6–23.9 mo and 24–47.9 mo/group , respectively , at baseline ( 2010 ) and n = ∼500 and 1100 children of the same age , respectively , at endline ( 2014 ) ] . We derived difference-in-difference impact estimates ( DDEs ) , adjusting for geographic clustering , infant age , sex , differences in baseline characteristics , and differential change in characteristics over time . Results : Groups were similar at baseline . CF improvements were significantly greater in the intensive than in the nonintensive group [ DDEs : 16.3 , 14.7 , 22.0 , and 24.6 percentage points ( pp ) for minimum dietary diversity , minimum meal frequency , minimum acceptable diet , and consumption of iron-rich foods , respectively ] . In the intensive group , CF practice s were high : 50.4 % for minimum acceptable diet , 63.8 % for minimum diet diversity , 75.1 % for minimum meal frequency , and 78.5 % for consumption of iron-rich foods . Timely introduction of foods improved . Significant , nondifferential stunting declines occurred in intensive ( 6.2 pp ) and nonintensive ( 5.2 pp ) groups in children 24–47.9 mo . Conclusions : The intensive program substantially improved CF practice s compared with the nonintensive program . Large-scale program delivery was feasible and , with the use of multiple platforms , reached 1.7 million households . Nondifferential impacts on stunting were likely due to rapid positive secular trends in Bangladesh . Accelerating linear growth further could require accompanying interventions . This study establishes proof of concept for large-scale behavior change interventions to improve child feeding . This trial was registered at clinical trials.gov as NCT01678716 Objective To assess the effectiveness of dietary counselling and complementary food supplements on anaemia and stunting prevalence in children aged 6–23 months . Design A controlled intervention study with measurements of height and haemoglobin levels , and cross-sectional surveys in August 2012 ( baseline ) , 2013 ( mid-term ) and 2014 ( end-line ) . Setting One intervention county and one control county in rural Qinghai Province , China . Intervention Complementary food supplements ( containing protein , fat , carbohydrate , vitamin A , B1 , B2 , B12 , D3 , folic acid , iron , zinc and calcium ) and complementary feeding counselling were given in the intervention county . Participants Caregivers and their children aged 6–23 months . Primary and secondary outcome measures Effect of the interventions on the prevalence of anaemia ( haemoglobin < 110 g/L ) and stunting ( z-score of height-for-age < −2.0 ) ( controlled for differences between the counties ) , and on infant feeding practice s. Results The surveys were conducted on 1804 , 2187 and 2186 children aged 6–23 months in the intervention county in August 2012 , 2013 and 2014 , respectively , and 804 , 680 and 790 children in the control county , respectively . Between the baseline and end-line surveys , anaemia prevalence decreased more in the intervention county than in the control county ( 71.1 % to 47.8 % vs 86.3 % to 75.3 % , respectively ; p<0.0001 ) . There was no difference in the decrease in stunting prevalence between the counties ( 9.7 % to 7.1 % vs 17.0 % to 15.0 % ; p=0.7954 ) . The proportions of children given iron-rich or iron-fortified food , introduced to ( semi- ) solid food at 6–8 months , and given food with minimum dietary diversity increased from 43.2 % to 88.8 % ( p<0.0001 ) , 81.4 % to 96 % ( p=0.0470 ) and 53.0 % to 59.8 % ( p<0.0001 ) , respectively in the intervention county . Conclusions We found much higher anaemia prevalence in poor rural areas of Qinghai Province compared with the national data . Community-based complementary food supplements combined with dietary counselling can improve feeding practice s and reduce anaemia prevalence . Future studies should use longer follow-up to assess the effects on stunting . Strengths and limitations We included a large number of participants and assessed a combined complementary food supplements and dietary counselling intervention in a poor rural area in China with high anaemia prevalence . Although the study took place in only one intervention county and one control county , we conducted an analysis that controlled for differences between the two counties . Also , although we made significant efforts to train village doctors , their education was not systematic ally assessed after training and thus their delivery of the interventions may have been variable . Trial registration number ChiCTRPRC12002444 ; Pre- results Despite substantial evidence of maternal and infant benefits of breastfeeding , adolescent mothers initiate breastfeeding less often and maintain breastfeeding for shorter duration s when compared to their adult counterparts . A r and omized controlled trial drawing on the theory of planned behavior and developmental theory was conducted to determine if an education and counseling intervention provided by a lactation consultant — peer counselor team increased breastfeeding initiation and duration up to 6 months postpartum among adolescent mothers . Study participants ( N = 289 ) enrolled from multiple prenatal clinic and school setting s , were 15 to 18 years old , and predominately African American , single , and primiparous . The intervention , which started in the second trimester of pregnancy and extended through 4 weeks postpartum , positively influenced breastfeeding duration ( p < .001 ) within the experimental group , but not breastfeeding initiation or exclusive breastfeeding rates . This education/support intervention was partially effective in enhancing breastfeeding outcomes . Implication s for research and practice are described OBJECTIVE The objective of the present study was to evaluate the effectiveness of an educational programme on healthy alimentation , carried out in day-care centres and aim ed at the parents of children from 1 to 2 years of age , regarding the acquisition of healthy eating habits among themselves and their children . DESIGN We performed a multicentre , multidisciplinary , r and omized controlled study in a community setting . SETTING The EniM study ( nutritional intervention study among children from Mataró ) was performed in twelve day-care centres in Mataró ( Spain ) . Centres were r and omized into a control group ( CG ) and an intervention group ( IG ) . IG received four or five educational workshops on diet , CG did not have workshops . SUBJECTS Children , not exclusively breast-fed , from 1 to 2 years of age , in the participating day-care centres and the persons responsible for their alimentation ( mother or father ) . RESULTS Thirty-five per cent of the IG did not attend the minimum of three workshops and were excluded . The CG included seventy-four children and seventy-two parents and the IG seventy-five children and sixty-seven parents . Both groups were comparable at baseline . Basal adherence to the Mediterranean diet was 56·4 % in parents ( Gerber index ) and 7·7 points in children ( Kidmed test ) . At 8 months , Mediterranean diet adherence had improved in the IG by 5·8 points in the Gerber index ( P=0·01 ) and 0·6 points in the Kidmed test ( P=0·02 ) compared with the CG . CONCLUSIONS This educational intervention performed in parents at the key period of incorporation of a 1 - 2-year-old child to the family table showed significant increases in adherence of the parents to the Mediterranean diet , suggesting future improvement in different indicators of health and an expected influence on the diet of their children OBJECTIVE : To assess the effectiveness of a parent-focused intervention on infants ’ obesity-risk behaviors and BMI . METHODS : This cluster r and omized controlled trial recruited 542 parents and their infants ( mean age 3.8 months at baseline ) from 62 first-time parent groups . Parents were offered six 2-hour dietitian-delivered sessions over 15 months focusing on parental knowledge , skills , and social support around infant feeding , diet , physical activity , and television viewing . Control group parents received 6 newsletters on nonobesity-focused themes ; all parents received usual care from child health nurses . The primary outcomes of interest were child diet ( 3 × 24-hour diet recalls ) , child physical activity ( accelerometry ) , and child TV viewing ( parent report ) . Secondary outcomes included BMI z-scores ( measured ) . Data were collected when children were 4 , 9 , and 20 months of age . RESULTS : Unadjusted analyses showed that , compared with controls , intervention group children consumed fewer grams of noncore drinks ( mean difference = –4.45 ; 95 % confidence interval [ CI ] : –7.92 to –0.99 ; P = .01 ) and were less likely to consume any noncore drinks ( odds ratio = 0.48 ; 95 % CI : 0.24 to 0.95 ; P = .034 ) midintervention ( mean age 9 months ) . At intervention conclusion ( mean age 19.8 months ) , intervention group children consumed fewer grams of sweet snacks ( mean difference = –3.69 ; 95 % CI : –6.41 to –0.96 ; P = .008 ) and viewed fewer daily minutes of television ( mean difference = –15.97 : 95 % CI : –25.97 to –5.96 ; P = .002 ) . There was little statistical evidence of differences in fruit , vegetable , savory snack , or water consumption or in BMI z-scores or physical activity . CONCLUSIONS : This intervention result ed in reductions in sweet snack consumption and television viewing in 20-month-old children OBJECTIVE To evaluate the impact that a program based on maternal dietary counseling covering breastfeeding and healthy complementary feeding had on the prevalence of iron deficiency , anemia and iron deficiency anemia in children aged 12 to 16 months . METHODS Newborn infants were r and omized at birth to an intervention or a control group . Mothers in the intervention group received home visits during the children 's first year of life on a monthly basis up to 6 months , and at 8 , 10 and 12 months . The mothers in the control group received visits for data collection when children reached 6 and 12 months . All children were visited at ages between 12 and 16 months and 24-hour dietary recalls and hemoglobin and ferritin tests were conducted . RESULTS There was no evidence that the intervention had an effect on anemia incidence , which was 66.5 % in the intervention group and 61.8 % in the control group . There was also no evidence of any difference between the groups in the prevalence of iron deficiency anemia or of iron deficiency . However , a higher percentage of children in the intervention group were exclusively breastfed at 4 and 6 months , and breastfed at 6 and 12 months . Intervention group children also consumed more meat and were fed diets with better iron bioavailability and consumed less cow 's milk and calcium than children from the control group . CONCLUSION This intervention had no effect on the prevalence of anemia , iron deficiency or iron deficiency anemia . Clinical trial registry identification number : NCT00629629 BACKGROUND Malnutrition is the underlying cause of half of child mortality . Many programmes attempt to remedy this issue but there is a lack of evidence on effective ways to decrease child malnutrition . METHODS We did a cluster-r and omised trial of an educational intervention in a poor periurban area ( ie , shanty town ) of Peru . Guided by formative research , the intervention aim ed to enhance the quality and coverage of existing nutrition education and to introduce an accreditation system in six government health facilities compared with six control facilities . The primary outcome measure was growth that was measured by weight , length , and Z scores for weight-for-age and length-for-age at age 18 months . Main secondary outcomes were the percentage of children receiving recommended feeding practice s and the 24-h dietary intake of energy , iron , and zinc from complementary food at ages 6 , 9 , 12 , and 18 months . Analysis was by intention to treat . FINDINGS We enrolled a birth cohort of 187 infants from the catchment areas of intervention centres and 190 from control areas . Caregivers in intervention areas were more likely to report receiving nutrition advice from the health service than were caregivers in control health facilities ( 16 [ 52 % ] of 31 vs 9 [ 24 % ] of 37 , p=0.02 ) . At 6 months more babies in intervention areas were fed nutrient-dense thick foods at lunch ( a recommended complementary feeding practice ) than were controls ( 48 [ 31 % ] of 157 vs 29 [ 20 % ] of 147 ; difference between groups 19 [ 11 % ] , p=0.03 ) . Fewer children in intervention areas failed to meet dietary requirements for energy ( 8 months : 30 [ 18 % ] of 170 vs 45 [ 27 % ] of 167 , p=0.04 ; 12 months : 64 [ 38 % ] of 168 vs 82 [ 49 % ] of 167 , p=0.043 ) , iron ( 8 months : 155 [ 91 % ] of 170 vs 161 [ 96 % ] of 167 , 9 months : 152 [ 93 % ] of 163 vs 165 [ 99 % ] of 166 , p=0.047 ) , and zinc ( 9 months : 125 [ 77 % ] of 163 vs 145 [ 87 % ] of 166 , p=0.012 ) than did controls . Children in control areas were more likely to have stunted growth ( ie , length for age less than 2 SD below the reference population median ) at 18 months than children in intervention groups ( 26 [ 16 % ] of 165 vs 8 [ 5 % ] of 171 ; adjusted odds ratio 3.04 [ 95 % CI 1.21 - 7.64 ] ) . Adjusted mean changes in weight gain , length gain , and Z scores were all significantly better in the intervention area than in the control area . INTERPRETATION Improvement of nutrition education delivered through health services can decrease the prevalence of stunted growth in childhood in areas where access to food is not a limiting factor OBJECTIVE Lack of diversity is a major factor contributing to inadequate nutrient intakes among children during the complementary feeding period in many rural areas in developing countries . This has been attributed to inadequate feeding practice s and nutrition knowledge among their caregivers . The aim of the present study was to assess the effect of an educational intervention on children 's dietary diversity and nutrition knowledge of caregivers . DESIGN Cluster r and omization was applied and twenty matched village pairs were r and omly assigned to the intervention or control group . The nutrition education intervention consisted of four sessions comprising of group trainings and cooking demonstrations that were conducted over a period of 5 months . SETTING Households in rural communities in Bondo and Teso South sub-counties , western Kenya . SUBJECTS Caregivers with children aged 6 - 17 months receiving nutrition education . RESULTS The children 's dietary diversity scores ( CDDS ) and nutrition knowledge scores of the caregivers improved significantly in the intervention group at endline . The treatment effect on CDDS was positive and significant ( P=0.001 ) . The CDDS rate of the children in the intervention group was 27 % larger than it would have been without the treatment effect . The intervention also had a significant effect on the caregivers ' nutrition knowledge scores ( incidence rate ratio=2.05 ; P<0.001 ) . However , the nutrition knowledge of the caregivers did not have a significant effect on CDDS ( P=0.731 ) . CONCLUSIONS The nutrition education intervention led to improvements in children 's dietary diversity and nutrition knowledge of the caregivers Objectives : To examine the effects of nutritional counseling for the infant diet focused on complementary feeding and total diet by use of dietary scores . Patients and Methods : In a r and omized controlled intervention trial , 183 mothers of full-term infants were allocated to 4 intervention groups ( IG0–IG3 ) . Intervention consisted of dietary counseling based on the food-based guidelines for infant nutrition in Germany . Counseling was done in 3 different forms : a telephone hotline ( IG1 ) , then written information ( IG2 ) , followed by additional personal telephone counseling ( IG3 ) . The IG0 group was not counseled at all . The actual diet of the infants was assessed by telephone interviews when the infants were 2 , 4 , 6 , 9 , and 12 months old and evaluated by food-based and meal-based dietary scores . Results : Plausible , although often not statistically significant , effects of counseling were found for several single scores at various age points . Total diet during the first year of life was significantly closer to the recommendations in the most intensively counseled group than in the noncounseled and lowest-counseled groups . Telephone counseling proved to be more effective than distribution of written material . Conclusions : The measured effects of the innovative approach of personal telephone counseling point to the advantages of giving dietary advice to mothers of infants by means of personal contacts and suggest that positive effects on dietary habits may even be greater by face-to-face talks between mothers and experts Background : Low dietary quality and quantity and inappropriate feeding practice s can cause undernutrition . Poor nutritional status in early childhood is associated with growth faltering . The objective of the study was to assess the potential of community-based nutrition education to improve height-for-age z-scores in children 6–23 months of age . Methods and Findings : We carried out a cluster-r and omized-controlled trial to assess the effectiveness of nutrition education . A total of 24 Extension Planning Area Sections served as clusters . The selection criteria were : the position of the extension officer was staffed and the sections had been selected by the project for activities in its first project year . The sections were r and omized into intervention and control restricted on mean height for age Z-score using baseline information . In the intervention area , food security activities and community-based nutrition education was implemented . The control area received food security activities only . At baseline ( 2011 ) and endline ( 2014 ) , caregivers with a child below two years of age were enrolled . Data assessment included anthropometric measurements , interviews on socio-economic status , dietary intake and feeding practice s. A difference-in-differences estimator was used to calculate intervention effects . A positive impact on child dietary diversity was observed ( B ( SE ) = 0.39 ( 0.15 ) , p = 0.01 ; 95%CI 0.09–0.68 ) . There was a non-significant positive intervention effect on mean height-for-age z-scores ( B ( SE ) = 0.17 ( 0.12 ) , p = 0.15 ; 95%CI -0.06–0.41 ) . Limitations : The 24h dietary recalls used to measure dietary diversity did not consider quantities of consumed foods . Unrecorded poor quality of consumed foods might have masked a potential benefit of increased child dietary diversity on growth . Conclusions : Participatory community-based nutrition education for caregivers improved child dietary diversity even in a food insecure area . Nutrition education should be part of programs in food insecure setting s aim ing at ameliorating food insecurity among communities OBJECTIVE To investigate the knowledge , attitude and practice ( KAP ) of young children 's mothers on infant feeding and to evaluate the effects of nutritional education in the rural areas . METHODS A cluster sampling method was used to select the local health station . Five hundred and fifteen mothers , who had infants with age of 4 - 6 months , were recruited for the question naire survey on the nutritional knowledge in rural areas of Tianjin municipality . The mothers were r and omly divided into intervention group I ( 160 ) , intervention group II ( 180 ) and control group ( 175 ) . The mothers in the intervention group I were educated with feeding guideline on infants and young children and had had Group lectures and advisory from experts about maternal and child nutrition for teaching them how to feed their children ; while , the mothers in the intervention group II were trained with feeding guideline on infants and young children by themselves ; and the mothers in the control group received routine guidance at the local health station . The follow-up evaluation on nutritional knowledge of the mothers in each group was carried out after 3 and 6 months intervention , respectively . RESULTS The educational background had significant effect on KAP scores : KAP scores of the mothers with primary education or less ( 8.3 + /- 2.2 ) were significantly lower than that of the mothers educated with high school ( 9.4 + /- 1.6 ) and university ( 9.6 + /- 1.8 ) ( LSD t = 3.70 , P < 0.001 ) . After being educated with feeding guideline on infants and young children , the knowledge of infant 's mothers was greatly improved and KAP scores of the mothers after intervention were higher than that of the baseline ( F = 183.556 , P = 0.006 ) ; the percentage of correct answer on nutrition knowledge in the intervention groups was significantly higher than that of the control group . At six months of intervention , the KAP scores of intervention group I ( 12.0 ) and intervention group II ( 11.6 ) were higher than that of the control group ( 10.5 ) ( LSD t = 5.96 , P < 0.001 ; LSD t = 4.25 , P < 0.001 ) . CONCLUSION Providing nutritional and health education to the infant 's mothers should be helpful for improving infant 's feeding pattern and ensuring the adequate growth and development of infants Objective : To evaluate a universal obesity prevention intervention , which commenced at infant age 4–6 months , using outcome data assessed 6 months after completion of the first of two intervention modules and 9 months from baseline . Design : R and omised controlled trial of a community-based early feeding intervention . Subjects and methods : Six hundred and ninety-eight first-time mothers ( mean age 30±5 years ) with healthy term infants ( 51 % male ) aged 4.3±1.0 months at baseline . Mothers and infants were r and omly allocated to self-directed access to usual care or to attend two group education modules , each delivered over 3 months , that provided anticipatory guidance on early feeding practice s. Outcome data reported here were assessed at infant age 13.7±1.3 months . Anthropometrics were expressed as z-scores ( WHO reference ) . Rapid weight gain was defined as change in weight-for-age z-score ( WAZ ) of > + 0.67 . Maternal feeding practice s were assessed via self-administered question naire . Results : There were no differences according to group allocation on key maternal and infant characteristics . At follow-up ( n=598 ( 86 % ) ) , the control group infants had higher BMI -for-age z-score ( BMI Z ) ( 0.42±0.85 vs 0.23±0.93 , P=0.009 ) and were more likely to show rapid weight gain from baseline to follow-up ( odds ratio (OR)=1.5 , confidence interval ( CI ) 95%=1.1–2.1 , P=0.014 ) . Mothers in the control group were more likely to report using non-responsive feeding practice s that fail to respond to infant satiety cues such as encouraging eating by using food as a reward ( 15 % vs 4 % , P=0.001 ) or using games ( 67 % vs 29 % , P<0.001 ) . Conclusions : These results provide early evidence that anticipatory guidance targeting the ‘ when , what and how ’ of solid feeding can be effective in changing maternal feeding practice s and , at least in the short term , reducing anthropometric indicators of childhood obesity risk . Analyses of outcomes at later ages are required to determine if these promising effects can be sustained OBJECTIVE To assess the effectiveness of the Melbourne Infant Feeding , Activity and Nutrition Trial ( InFANT ) Program according to maternal education and age . METHODS A cluster-r and omised controlled trial involving 542 mother/infant pairs from 62 existing first-time parent groups was conducted in 2008 in Melbourne , Australia . The intervention involved 6 × 2-hour dietitian-delivered sessions , DVD and written re sources from infant age 4 - 15 months . Outcomes included infant diet ( 3 × 24 h diet recalls ) , physical activity ( accelerometry ) , television viewing and body mass index . We tested for moderation by maternal education ( with/without a University degree ) and age ( < 32 and ≥ 32 years ) . The trial was registered with the IS RCT N Register ( identifier 81847050 ) . RESULTS Interaction effects with the treatment arm were observed for maternal education and age . The intervention effects on vegetable ( positive effect ) and sweet snack consumption ( negative effect ) were greater in children with higher educated mothers while intervention effects on water consumption ( positive effect ) were greater in infants with lower educated mothers . The intervention was also more effective in increasing both vegetable and water consumption in infants with mothers aged < 32 years . CONCLUSIONS Child obesity prevention interventions may be differentially effective according to maternal education and age . Evidence of differential effects is important for informing more sensitively targeted/tailored approaches The impact on vitamin A deficiency ( VAD ) , wasting malnutrition , and excessive childhood mortality of two alternative approaches-nutrition education and mega-dose capsule distribution ( 6 - 12-month-olds : 100,000 IU ; 1 - 5-year-olds : 200,000 IU)-in communities in Nepal are compared . Approximately 40,000 children from 75 locations in seven districts in two ecological setting s ( lowl and and hills ) took part in the study and were r and omly allocated to intervention cohorts or a control group . At 24 months after the implementation of the project the reduction of risk for xerophthalmia was greater among children whose mothers were able to identify vitamin-A-rich foods ( relative risk ( RR ) = 0.25 ; 95 % confidence interval ( CI ) = 0.10 - 0.62 ) than among the children who received mega-dose capsules ( RR = 0.59 ; 95 % CI = 0.41 - 0.84 ) . The risk of mortality at 2 years was reduced for both the nutrition education ( RR = 0.64 ; 95 % Cl = 0.48 - 0.86 ) and capsule distribution ( RR = 0.57 ; 95 % CI = 0.42 - 0.77 ) cohorts . The nutrition education programme was , however , more expensive to deliver than the capsule distribution programme . High rates of participation for children in the supplementation programme were achieved quickly . The nutrition education messages also spread rapidly throughout the study population ( regardless of intervention cohort assignment ) . Practice s , however , were slower to change . In communities where maternal literacy was low and channels of communication were limited the capsule distribution programme appeared to be more economical . However , there are economies of scale for nationwide education programmes that do not exist for capsule distribution programmes . Although nutrition education provides economies of scale and the promise of long-term sustainability , a comprehensive national programme requires both dietary supplementation and nutrition education components This study assesses the impact of an intervention known as the Ten Steps to Healthy Feeding : A Nutritional Guide for Children under Two on nutritional conditions and infant health in low-income families . Two hundred newborns were r and omized to the intervention group and three hundred to the control group . Parents of the intervention group received nutritional orientation during the child 's first year of life . Both groups received visits at 6 and 12 months and routine follow-up by their pediatricians . The results ( n = 397 ) showed that the intervention was associated with a higher proportion of exclusive breastfeeding at 4 months ( RR = 1.58 ; 95%CI : 1.21 - 2.06 ) and 6 months ( RR = 2.34 ; 95%CI : 1.37 - 3.99 ) and breastfeeding at 12 months ( RR = 1.26 ; 95%CI : 1.02 - 1.55 ) and a lower proportion of children with diarrhea ( RR = 0.68 ; 95%CI : 0.51 - 0.90 ) , respiratory problems ( RR = 0.63 ; 95%CI : 0.46 - 0.85 ) , use of medication ( RR = 0.56 ; 95%CI : 0.34 - 0.91 ) , and dental caries ( RR = 0.56 ; 95%CI : 0.32 - 0.96 ) in the 12 - 16 month bracket . The intervention had no effect on the occurrence of anemia , hospitalization , or nutritional status . The results suggest that the nutritional orientation program led to positive changes in infant feeding practice s and health conditions , but that it was insufficient to prevent iron deficiency anemia INTRODUCTION Although the disadvantages of introducing non-breast milk and the early introduction of complementary foods are known , such practice s are common worldwide . OBJECTIVE To evaluate the efficacy of counseling about breastfeeding and complementary feeding in preventing the introduction of non-breast milk and complementary foods in the first 6 months . METHODS This r and omized clinical trial enrolled 323 adolescent mothers and their newborns and 169 maternal gr and mothers ; 163 mothers and 88 gr and mothers received five counseling sessions on breastfeeding while in the hospital and at 7 , 15 , 30 , and 60 days , and one session on complementary feeding at 120 days . Data about infant feeding were collected monthly . The impact was evaluated by comparing the Kaplan-Meier survival curves for the time of introduction of non-breast milk and complementary foods of the control and intervention groups . Median time of introduction of milk was calculated in the two groups . RESULTS The survival curves showed that the intervention postponed the introduction of non-breast milk and complementary foods . At 4 months , 41 % ( 95 % CI , 32.8 - 49.2 ) of the infants in the control group received complementary foods in comparison to 22.8 % ( 95 % CI , 15.9 - 29.7 ) of the intervention group . Counseling postponed the introduction of non-breast milk , which occurred at 95 days ( 95 % CI , 8.7 - 111.3 ) in the control group and at 153 days ( 95 % CI , 114.6 - 191.4 ) in the intervention group . CONCLUSIONS Counseling sessions on infant 's first 4 months were an efficacious strategy to prevent the introduction of non-breast milk and complementary foods in the 6 months of life OBJECTIVE To evaluate the impact of a dietary counseling in reducing the intake of energy-dense foods by infants . DESIGN A r and omized controlled trial . SETTING AND PARTICIPANTS São Leopoldo , Brazil . Mothers and infants of a low-income-group population were r and omized into intervention ( n = 163 ) and received dietary counseling during 10 home visits , or control ( n = 234 ) groups . MAIN OUTCOMES MEASURES Child consumption of sugar-dense ( SD ) and lipid-dense ( LD ) foods at 12 to 16 months . ANALYSIS The effect of the intervention was expressed by relative risks and 95 % confidence intervals . Poisson regression analysis was used to determine the association between exclusive breastfeeding and the energy-dense foods intake . RESULTS A smaller proportion of infants from the intervention group consumed c and y , soft drinks , honey , cookies , chocolate , and salty snacks . In the intervention group , there was a reduction of 40 % and 50 % in the proportion of infants who consumed LD and SD foods , respectively . Being breastfed up to 6 months reduced the risk for consumption of LD and SD foods by 58 % and 67 % , respectively . CONCLUSIONS AND IMPLICATION S Dietary counseling to mothers may be effective in reducing the consumption of energy-dense foods among infants , and it is helpful in improving early dietary habits Importance Baby-led approaches to complementary feeding , which promote self-feeding of all nonliquid foods are proposed to improve energy self-regulation and lower obesity risk . However , to date , no r and omized clinical trials have studied this proposition . Objective To determine whether a baby-led approach to complementary feeding results in a lower body mass index ( BMI ) than traditional spoon-feeding . Design , Setting , and Participants The 2-year Baby-Led Introduction to Solids ( BLISS ) r and omized clinical trial recruited 206 women ( 168 [ 81.6 % ] of European ancestry ; 85 [ 41.3 % ] primiparous ) in late pregnancy from December 19 , 2012 , through March 17 , 2014 , as part of a community intervention in Dunedin , New Zeal and . Women were r and omized to a control condition ( n = 101 ) or the BLISS intervention ( n = 105 ) after stratification for parity and education . All outcomes were collected by staff blinded to group r and omization , and no participants withdrew because of an adverse event . Data were analyzed based on intention to treat . Interventions Mothers in the BLISS group received lactation consultant support ( ≥5 contacts ) to extend exclusive breastfeeding and delay introduction of complementary foods until 6 months of age and 3 personalized face-to-face contacts ( at 5.5 , 7.0 , and 9.0 months ) . Main Outcomes and Measures The primary outcome was BMI z score ( at 12 and 24 months ) . Secondary outcomes included energy self-regulation and eating behaviors assessed with question naires at 6 , 12 , and 24 months and energy intake assessed with 3-day weighed diet records at 7 , 12 , and 24 months . Results Among the 206 participants ( mean [ SD ] age , 31.3 [ 5.6 ] years ) , 166 were available for analysis at 24 months ( retention , 80.5 % ) . The mean ( SD ) BMI z score was not significantly different at 12 months ( control group , 0.20 [ 0.89 ] ; BLISS group , 0.44 [ 1.13 ] ; adjusted difference , 0.21 ; 95 % CI , −0.07 to 0.48 ) or at 24 months ( control group , 0.24 [ 1.01 ] ; BLISS group , 0.39 [ 1.04 ] ; adjusted difference , 0.16 ; 95 % CI , −0.13 to 0.45 ) . At 24 months , 5 of 78 infants ( 6.4 % ) were overweight ( BMI ≥95th percentile ) in the control group compared with 9 of 87 ( 10.3 % ) in the BLISS group ( relative risk , 1.8 ; 95 % CI , 0.6 - 5.7 ) . Lower satiety responsiveness was observed in BLISS infants at 24 months ( adjusted difference , −0.24 ; 95 % CI , −0.41 to −0.07 ) . Parents also reported less food fussiness ( adjusted difference , −0.33 ; 95 % CI , −0.51 to −0.14 ) and greater enjoyment of food ( adjusted difference , 0.25 ; 95 % CI , 0.07 to 0.43 ) at 12 months in BLISS infants . Estimated differences in energy intake were 55 kJ ( 95 % CI , −284 to 395 kJ ) at 12 months and 143 kJ ( 95 % CI , −241 to 526 kJ ) at 24 months . Conclusions and Relevance A baby-led approach to complementary feeding did not result in more appropriate BMI than traditional spoon-feeding , although children were reported to have less food fussiness . Further research should determine whether these findings apply to individuals using unmodified baby-led weaning . Trial Registration http://anzctr.org.au Identifier : Few trials have shown that promoting complementary feeding among young children is effective in improving child linear growth in re source -challenged setting s. We design ed a community-based participatory nutrition promotion ( CPNP ) programme adapting a Positive Deviance/Hearth approach that engaged mothers in 2-week nutrition sessions using the principles of ' learning by doing ' around child feeding . We aim ed to test the effectiveness of the CPNP for improving child growth in rural Ethiopia . A cluster r and omized trial was implemented by adding the CPNP to the existing government nutrition programmes ( six clusters ) vs. government programmes only ( six clusters ) . A total of 1790 children aged 6 to 12 months ( 876 in the intervention and 914 in the control areas ) were enrolled and assessed on anthropometry every 3 months for a year . Multi-level mixed-effect regression analysis of longitudinal outcome data ( n = 1475 ) examined the programme impact on growth , adjusting for clustering and enrollment characteristics . Compared with children 6 to 24 months of age in the control area , those in the intervention area had a greater increase in z scores for length-for-age [ difference ( diff ) : 0.021 z score/month , 95 % CI : 0.008 , 0.034 ] and weight-for-length ( diff : 0.042 z score/month , 95 % CI : 0.024 , 0.059 ) . At the end of the 12-month follow-up , children in the intervention area showed an 8.1 % ( P = 0.02 ) and 6.3 % ( P = 0.046 ) lower prevalence of stunting and underweight , respectively , after controlling for differences in the prevalence at enrollment , compared with the control group . A novel CPNP programme was effective in improving child growth and reducing undernutrition in this setting . © 2016 John Wiley & Sons OBJECTIVES : The goal of this study was to determine if a responsive stimulation and feeding intervention improved developmental and nutritional outcomes compared with a regular information-based parenting program . The hypothesis was that mothers in the intervention would exhibit better parenting skills and children would exhibit better developmental and nutritional outcomes than controls . METHODS : A cluster-r and omized field trial was conducted with 302 children aged 8 to 20 months and their mothers in rural Bangladesh who were r and omly assigned according to village to 1 of 3 groups . The control mothers received 12 informational sessions on health and nutrition . The intervention groups received an additional 6 sessions delivered by peer educators who included modeling and coached practice in self-feeding and verbal responsiveness with the child during play . A second intervention group received , along with the sessions , 6 months of a food powder fortified with minerals and vitamins . Developmental outcomes included the Home Observation for Measurement of the Environment ( HOME ) Inventory , mother-child responsive talk , and language development . Nutritional outcomes included weight , height , self-feeding , and mouthfuls eaten . We used analysis of covariance to compare the 3 groups at the posttest and at follow-up , covarying the pretest levels and confounders . RESULTS : At follow-up , responsive stimulation-feeding groups had better HOME inventory scores , responsive talking , language , mouthfuls eaten , and h and -washing . Micronutrient fortification result ed in more weight gain . CONCLUSIONS : A brief behavior-change program that focused on modeling and practice in stimulation and feeding was found to benefit children 's nutrition and language development . Micronutrients benefited children 's weight but not length Objective : To carry out a community-based research approach to determine the most effective educational interventions to reduce smoking among African-American smokers . The intervention included preparation of the community , planning and developing a model of change , and developing a community-based intervention . The study population consisted of 2,544 r and omly selected adult African-American smokers residing in four sites in the northeastern and southeastern parts of the United States . The research design provided a comparison of active intervention sites with passive control sites as well as low income and moderate income areas . Major Outcome Measures : Point prevalence of non-smoking at the time of interview ; Period prevalence of non-smoking at the time of interview ; Period prevalence of quit attempts in the prior six months ; Number of smoke-free days in the prior six months ; Number of cigarettes smoked daily at the time of interview . Results : Based upon a survey eighteen months after baseline data was collected , all four measures of cigarette smoking behavior showed a strong statistically significant reduction of personal smoking behavior among those receiving active interventions versus the passive group . On the basis of process variable analysis , direct contact with the project staff in the prior six months was significantly higher in the active intervention areas . There was only a small non-significant increase in personal smoking behavior in moderate income groups as opposed to low income groups . Conclusion : An analysis of process variables strongly suggests that , within this African-American Community , “ h and s on ” or “ face to face ” approaches along with mass media , mailings , and other less personal approaches were more effective in reducing personal smoking behavior than media , mailings , and other impersonal approaches alone addressed to large audiences BACKGROUND Despite an extensive well-child health service , 30 % of New Zeal and 's 2- to 4-y old children are overweight or obese . This suggests that additional intervention is necessary to establish healthy nutrition behaviors . OBJECTIVE The aim of this study was to assess the effect of intervention from 0 to 18 mo of age on food and nutrient intake , eating behaviors , and parental feeding practice s in 18- to 24-mo-old children . DESIGN In total , 802 families with healthy infants were r and omly allocated to 1 of 4 groups : Usual Care ( UC ) ; Food , Activity , and Breastfeeding ( FAB ) ; Sleep ; or FAB and Sleep ( Combination ) . All groups received st and ard " well-child " care . The FAB intervention comprised 7 - 8 additional contacts for education and support around breastfeeding , food , and activity . The Sleep intervention comprised 2 additional contacts for guidance about sleeping habits . Combination families received both interventions . A vali date d food-frequency question naire assessed food intake at 2 y. A question naire assessed eating behaviors and parental feeding practice s at 18 and 24 mo . RESULTS At 2 y , there were no statistically significant differences in food and nutrient intake or eating behaviors in the groups receiving the FAB intervention ( FAB , Combination ; 325 children ) compared with the groups who did not ( Sleep , UC ; 341 children ) . With the use of a 5-point scale , small but statistically significant differences in parental feeding practice s were observed in the groups receiving the FAB intervention : greater child control over eating ( difference : 0.14 ; 95 % CI : 0.02 , 0.26 ) and less pressure to eat ( difference : 0.18 ; 95 % CI : 0.04 , 0.32 ) at 18 mo , as well as greater encouragement of nutrient-dense foods at 24 mo ( difference : 0.16 ; 95 % CI : 0.03 , 0.30 ) . No statistically significant differences were observed between the groups who received the Sleep intervention ( Sleep , Combination ; 313 children ) and those who did not , except higher meat intake in the former ( 11 g/d ) . CONCLUSION Additional education and support for parents from birth did not improve nutrition behaviors in this population at 2 y of age . This trial was registered at clinical trials.gov as NCT00892983 This prospect i ve r and omized trial was carried out to test the efficacy of a specific intervention for reducing the extent of their malnutrition and to change behaviour of mothers relating to child-feeding practice s , care-giving , and health-seeking practice s under the Bangladesh Integrated Nutrition Project ( BINP ) . The study was conducted in rural Bangladesh among 282 moderately-malnourished ( weight-for-age between 61 % and 75 % of median of the National Center for Health Statistics st and ard ) children aged 6 - 24 months . Mothers of the first intervention group received intensive nutrition education ( INE group ) twice a week for three months . The second intervention group received the same nutrition education , and their children received additional supplementary feeding ( INE+SF group ) . The comparison group received nutrition education from the community nutrition promoters twice a month according to the st and ard routine service of BINP . The children were observed for a further six months . After three months of interventions , a significantly higher proportion of children in the INE and INE+SF groups improved ( 37 % and 47 % respectively ) from moderate to mild or normal nutrition compared to the comparison group ( 18 % ) ( p < 0.001 ) . At the end of six months of observation , the nutritional status of children in the intervention groups improved further from moderate to mild or normal nutrition compared to the comparison group ( 59 % and 86 % vs 30 % , p < 0.0001 ) . As the intensive nutrition education and supplementation given were highly effective , more children improved from moderate malnutrition to mild or normal nutritional status despite a higher incidence of morbidity . The frequency of child feeding and home-based complementary feeding improved significantly ( p < 0.001 ) in both the intervention groups after three months of interventions and six months of observation . Body-weight gain was positively associated with age , length-for-age , weight-for-length , frequency of feeding of khichuri , egg , and potato ( p < 0.05 ) . Ability of mothers to identify malnutrition improved from 15 % to 99 % in the INE group and from 15 % to 100 % in the INE+SF group , but reduced from 24 % to 21 % in the comparison group . Use of separate feed pots , frequency of feeding , and cooking of additional complementary feeds improved significantly in the INE and INE+SF groups compared to the comparison group after three months of interventions and six months of observation . It can be concluded from the findings of the study that intensive nutrition education significantly improves the status of moderately-malnourished children with or without supplementary feeding OBJECTIVE A community-based , r and omized trial was design ed to compare the effect of nutrition education and /or iron supplementation ( weekly ) on iron status of children in an urban slum in Delhi . METHODS Four hundred and fifty one children , 9 - 36 months of age and their caretakers ( mothers ) , assigned to one of the following groups were included in the cohort . Group 1 , nutrition education . Group 2 , supplementation ( with 20 mg elemental iron ) . Group 3 , nutrition education with supplementation ( with 20 mg elemental iron ) and Group 4 , control given placebo . The intervention program was of four months duration , with a treatment phase of 8 wk followed by 8 wk of no treatment . RESULTS Post intervention , at 8 wk and at 16 wk , the hemoglobin change in the nutrition education , supplementation , nutrition education with supplementation and control groups was 2.9 , 1.9 , 3.8 and -5.9 % , respectively and 2.1 , -1.9 , 0 and -9.3 % , respectively ( as compared to initial values ) . There was no significant effect of any of the intervention at 8 weeks . At 16 wk , there was significant positive effect of nutrition education group ( p less than 0.05 ) . The percent change in serum ferritin value at 16 wk in the nutrition education , supplementation , nutrition education with supplementation and control groups was 5.7 , -2.3 , -3.4 and -40 % , respectively . Serum ferritin values were significantly higher for the nutrition education group ( p < 0.001 ) as compared to the control . At 16 wk , the nutrition education group mothers showed significantly higher nutrition knowledge and the dietary iron intake of children was significantly higher than their control group counterparts ( p < 0.0001 ) . CONCLUSION The study suggests that nutrition education did have a positive effect on the iron status possibly by improving the dietary iron intake OBJECTIVE To evaluate a nutrition education intervention design ed to improve infant growth and feeding practice s. DESIGN An intervention study using monthly nutrition education delivered by locally trained counsellors targeted at caregivers of infants aged 5 - 11 months . Comparison of outcomes for 2 groups -- one non-intervention group of infants enrolled in 1997 that did not receive the intervention in the first year of life , and an intervention group of infants enrolled 1998 - 1999 that received the nutrition education . SETTING 11 r and omly selected and 2 purposively selected villages of south Karnataka . SUBJECTS 138 Infants ( n = 69 intervention ) aged 5 - 11 months . METHODS Families were administered a monthly question naire on feeding and child care behavior , and study infants were weighed at this time , using the SECA solar scales , developed for UNICEF . Logistic regression was used to examine differences between intervention and non-intervention infants in infant feeding behavior outcomes . RESULTS Statistically significant improvement was found in weight velocity for female infants in the intervention group . These infants were also more likely to exhibit at least four positive feeding behaviors -- intervention infants had a higher mean daily feeding frequency ( more likely to be fed solids at least four times a day ( OR = 4.35 , 95 % CI = 1.96 , 10.00 ) , higher dietary diversity ( more likely to receive a more diverse diet OR = 3.23 , 95 % CI = 1.28 , 7.69 ) , and were more likely to be fed foods suggested by the counsellors such as bananas ( OR = 10.00 , 95 % = 2.78 , 33.3 ) compared to non-intervention infants . CONCLUSION Nutrition education and counselling was significantly associated with increased weight velocity among girls and improved feeding behavior among both boys and girls . These results provide further evidence that community-based nutrition programs that emphasise appropriate feeding and care behavior can be used to prevent and address early childhood malnutrition in poor households In Ethiopia many women do not practice appropriate complementary feeding ( CF ) . The Health Belief Model ( HBM ) asserts that change in behavior is determined after consideration of severity , benefit , and barriers to change . This study examined the effectiveness of 3 months of HBM-based education compared to the traditional ( didactic ) method on CF practice s of mothers , with no education as control , using three r and omized groups . One hundred sixty-six mother-infant ( 6–18 months ) pairs were recruited . At baseline and after intervention , knowledge , perceptions , and practice s about CF and related areas were determined . It was only diet diversity that increased significantly in the HBM group ( from 3.05 ± 0.94 food groups to 3.79 ± 0.82 , p < .05 ) while the other two groups had no change . Improvements in food groups were most noticeable as legumes & nuts ( from 35.6 % use to 83.9 % in HBM group ) . Thus , nutrition education about diet diversity improvement needs to be conducted promotes behavior change OBJECTIVE To investigate whether educational modules presented on a touchscreen computer increase immediate nutrition and feeding knowledge in low-income , Spanish-speaking Latino immigrant parents . METHODS This was a r and omized controlled trial conducted in an urban pediatric clinic with a sample of low-income , Spanish-speaking Latino parents of children <3 years r and omly assigned to the intervention ( n = 80 ) and control groups ( n = 80 ) . Intervention group members viewed 5 modules on nutrition and feeding presented on an interactive platform using a touchscreen computer . Modules contained text , pictures , and audio . Content was drawn from Bright Futures Guidelines . The primary outcome was a parental total summed knowledge score based on correct responses to 19 questions related to module content . Domain-specific scores were also analyzed . RESULTS Intervention and control groups did not differ on demographic characteristics . Participants were of varied Latino origins , mean age was 27.5 years , 41 % reported a < 7th grade education , and 65 % reported that they rarely/never use a computer . Compared with the control group , the intervention group had a superior mean total summed knowledge score ( 72.3 % vs 90.8 % , P < .001 ) . Mean domain-specific summed knowledge scores were also greater in the intervention arm compared with the control for all 5 domains . These results did not differ on the basis of participant education level . 71 % ( n = 57 ) of intervention arm participants planned to change something based on what they learned from the computer program , and 80 % reported that they will ( n = 49 ) or may ( n = 15 ) talk to their child 's doctor about what they learned in the modules . CONCLUSIONS Results of this pilot study add to the growing literature on the use of this technology for health education in low-income Latino immigrants . Despite low education levels and computer experience , findings suggest that immediate parental knowledge was enhanced supporting the need for a more rigorous evaluation of this technology and its impact on health behaviors Responsive complementary feeding , whereby the mother feeds her child in response to child cues and psychomotor abilities , is low in some countries and likely contributes to malnutrition . Interventions are needed to evaluate whether promoting responsive feeding would add any benefit . Using a cluster-r and omized field trial , we evaluated a 6-session educational program that emphasized the practice of child self-feeding and maternal responsiveness . A total of 108 mothers and their 8- to 20-mo-old children in 19 clusters were r and omly assigned to the intervention group and 95 in 18 clusters were assigned to the informational control group . Outcomes were assessed at pretest , postintervention , and follow-up . Research assistants , who were unaware of group assignment , observed and coded mother and child midday meal behaviors . At follow-up , the percent of self-fed mouthfuls was 47.8 + /- 42.4 ( mean + /- SD ) in the responsive feeding group children compared with 32.2 + /- 41.0 in the controls ( P = 0.01 ) ; likewise , the number of responsive verbalizations was 6.55 + /- 5.9 in the responsive feeding mothers and 4.62 + /- 4.5 in controls ( P = 0.01 ) . Intervention mothers recalled more messages . Mouthfuls of food eaten by children and weight were equivalent in the 2 groups . Lack of change in foods eaten and small quantities may explain the similarly low levels of weight gain . These results provide evidence that self-feeding and maternal verbal responsiveness , two developmentally important behaviors , can be increased by targeting specific behaviors with appropriate behavior change strategies of modeling and coached practice . Weight gain may require more nutritional input , especially in areas of high food insecurity Background Nutritious complementary foods are needed in countries where undernutrition and stunting are major problems , but mothers may be reluctant to change from traditional gruels . Objective To test whether a recipe-based complementary feeding education intervention would improve knowledge and practice of mothers with young children in Hula , Ethiopia . Methods A baseline survey of 200 eligible , r and omly selected mother — child pairs gathered data on sociodemographic characteristics , food security status , knowledge and practice s concerning complementary feeding , food group intakes of children aged 6 to 23 months by 24-hour recalls , and children 's anthropometric measurements . Twice a month for 6 months , women in the intervention group received an education session consisting of eight specific messages using Alive and Thrive posters and a demonstration and tasting of a local barley and maize porridge recipe containing 30 % broad beans . The control group lived in a different area and had no intervention . Results At 6 months , knowledge and practice scores regarding complementary feeding were significantly improved ( p < .001 ) in the intervention group but not in the control group . The intervention result ed in improvement of children 's dietary diversity , as well as mean intake of energy and selected nutrients , compared with children in the control group . Changes in height and weight did not differ between the two groups . Conclusions Community-based nutrition education over 6 months that included demonstration of a local porridge recipe with broad beans added improved the complementary feeding practice s of caregivers and the nutritional status of their young children Background Despite the recent international focus on maternal and child nutrition , little attention is paid to nutrition capacity development . Although infant feeding counselling by health workers increases caregivers ’ knowledge , and improves breastfeeding , complementary feeding , and children ’s linear growth , most of the counselling in sub-Saharan Africa is primarily conducted by nurses or volunteers , and little is done to develop capacity for nutrition at the professional , organizational , or systemic levels . The Cameroon Baptist Convention Health Services Nutrition Improvement Program ( NIP ) has integrated a cadre of nutrition counselors into prevention of mother-to-child transmission of HIV programs , infant welfare clinics , and antenatal clinics to improve infant and young child feeding practice s ( IYCF ) . The study objective was to evaluate the effects of NIP ’s infant feeding counselors on exclusive breastfeeding ( EBF ) , complementary feeding ( CF ) , and children ’s linear growth . Methods A cross-sectional evaluation design was used . Using systematic r and om sampling , caregivers were recruited from NIP sites ( n = 359 ) and non-NIP sites ( n = 415 ) from Infant Welfare Clinics ( IWCs ) in the Northwest ( NWR ) and Southwest Regions ( SWR ) of Cameroon between October 2014 and April 2015 . Differences in EBF and CF practice s and children ’s linear growth between NIP and non-NIP sites were determined using chi-square and multiple logistic regression . Results After adjusting for differences in religion , occupation , and number of months planning to breastfeed , children were almost seven times ( Odds Ratio [ OR ] : 6.9 ; 95 % Confidence Interval [ CI ] : 2.30 , 21.09 ; β = 1.94 ) more likely to be exclusively breastfed at NIP sites compared to non-NIP sites . After adjusting for differences in occupation , religion , number of months planning to breastfeed , rural environment , economic status , attending other Infant Welfare Clinics , and non-biological caregiver , children were five times ( OR : 5.5 ; CI : 3.37 , 9.02 ; β = 1.71 ) more likely to be stunted at non-NIP sites compared to non-NIP sites . Conclusion Training a cadre of nutrition counselors is one approach towards increasing nutrition human re sources to implement nutrition interventions to improve maternal and child nutrition . In this research project , the study design did not allow for conclusive results , but rather suggest IYCF counseling provided by nutrition counselors was effective in increasing EBF and reduced the risk of stunting in children 6–8 months OBJECTIVE To assess the effectiveness of a home-based early intervention on infant feeding practice s and " tummy time " for infants in the first year of life . DESIGN R and omized controlled trial with follow-up measures scheduled at 6 and 12 months . SETTING Socially and economically disadvantaged areas of Sydney , Australia . PARTICIPANTS We recruited 667 first-time mothers and their infants in 2007 and 2008 . INTERVENTIONS The intervention consisted of 5 or 6 home visits from a specially trained research nurse delivering a staged home-based intervention in the antenatal period and at 1 , 3 , 5 , 9 , and 12 months . MAIN OUTCOME MEASURE Changes in infant feeding practice s and " tummy time . " RESULTS The intervention group had a significantly higher median duration of breastfeeding at 12 months than the control group ( 17 weeks [ 95 % confidence interval , 13.9 - 20.4 weeks ] vs 13 weeks [ 95 % confidence interval , 10.1 - 15.0 weeks ] ; P = .03 ) . Compared with the control group , the hazard ratio for stopping breastfeeding in the intervention group was 0.82 ( 95 % confidence interval , 0.68 - 0.99 ) . The intervention also result ed in a significantly later introduction of solid foods ( P < .001 for trend ) , reducing the proportion of mothers who introduced solids before 6 months by 12 % ( 95 % confidence interval , 4%-20 % ) from 74 % to 62 % . The intervention also decreased the age at which infants started tummy time ( P = .03 for trend ) and increased the daily practice of tummy time by 7 % from 76 % to 83 % ( P = .05 ) . CONCLUSION The home-based early intervention delivered by trained community nurses significantly improved some infant feeding practice s and result ed in earlier daily practice of tummy time . TRIAL REGISTRATION anzctr.org.au Identifier : ACTRN012607000168459 BACKGROUND Health consumers increasingly want access to accurate , evidence -based information about their medications . Currently , education about medications ( that is , information that is design ed to achieve health or illness related learning ) is provided predominantly via spoken communication between the health provider and consumer , sometimes supplemented with written material s. There is evidence , however , that current educational methods are not meeting consumer needs . Multimedia educational programs offer many potential advantages over traditional forms of education delivery . OBJECTIVES To assess the effects of multimedia patient education interventions about prescribed and over-the-counter medications in people of all ages , including children and carers . SEARCH METHODS We search ed the Cochrane Central Register of Controlled Trials ( CENTRAL , The Cochrane Library 2011 , Issue 6 ) , MEDLINE ( 1950 to June 2011 ) , EMBASE ( 1974 to June 2011 ) , CINAHL ( 1982 to June 2011 ) , PsycINFO ( 1967 to June 2011 ) , ERIC ( 1966 to June 2011 ) , ProQuest Dissertation & Theses Data base ( to June 2011 ) and reference lists of articles . SELECTION CRITERIA R and omised controlled trials ( RCTs ) and quasi- RCTs of multimedia-based patient education about prescribed or over-the-counter medications in people of all ages , including children and carers , if the intervention had been targeted for their use . DATA COLLECTION AND ANALYSIS Two review authors independently extracted data and assessed the risk of bias of included studies . Where possible , we contacted study authors to obtain missing information . MAIN RESULTS We identified 24 studies that enrolled a total of 8112 participants . However , there was significant heterogeneity in the comparators used and the outcomes measured , which limited the ability to pool data . Many of the studies did not report sufficient information in their methods to allow judgment of their risk of bias . From the information that was reported , three of the studies had a high risk of selection bias and one was at high risk of bias due to lack of blinding of the outcome assessors . None of the included studies reported the minimum clinical ly important difference for the outcomes that were measured . We have therefore reported results from the studies but have been unable to interpret whether differences were of clinical importance .The main findings of the review are as follows . Knowledge : There is low quality evidence that multimedia education was more effective than usual care ( non-st and ardised education provided as part of usual clinical care ) or no education ( st and ardised mean difference ( SMD ) 1.04 , 95 % confidence interval ( CI ) 0.49 to 1.58 , six studies with 817 participants ) . There was considerable statistical heterogeneity ( I(2 ) = 89 % ) , however , all but one of the studies favoured the multimedia group . There is moderate quality evidence that multimedia education was not more effective at improving knowledge than control multimedia interventions ( i.e. multimedia programs that do not provide information about the medication ) ( mean difference ( MD ) of knowledge scores 2.78 % , 95 % CI -1.48 to 7.0 , two studies with 568 participants ) . There is moderate quality evidence that multimedia education was more effective when added to a co-intervention ( written information or brief st and ardised instructions provided by a health professional ) compared with the co-intervention alone ( MD of knowledge scores 24.59 % , 95 % CI 22.34 to 26.83 , two studies with 381 participants ) .Skill acquisition : There is moderate quality evidence that multimedia education was more effective than usual care or no education ( MD of inhaler technique score 18.32 % , 95 % CI 11.92 to 24.73 , two studies with 94 participants ) and written education ( risk ratio ( RR ) of improved inhaler technique 2.14 , 95 % CI 1.33 to 3.44 , two studies with 164 participants ) . There is very low quality evidence that multimedia education was equally effective as education by a health professional ( MD of inhaler technique score -1.01 % , 95 % CI -15.75 to 13.72 , three studies with 130 participants ) .Compliance with medications : There is moderate quality evidence that there was no difference between multimedia education and usual care or no education ( RR of complying 1.02 , 95 % CI 0.96 to 1.08 , two studies with 4552 participants ) .We could not determine the effect of multimedia education on other outcomes , including patient satisfaction , self-efficacy and health outcomes , due to an inadequate number of studies from which to draw conclusions . AUTHORS ' CONCLUSIONS This review provides evidence that multimedia education about medications is more effective than usual care ( non-st and ardised education provided by health professionals as part of usual clinical care ) or no education , in improving both knowledge and skill acquisition . It also suggests that multimedia education is at least equivalent to other forms of education , including written education and education provided by a health professional . However , this finding is based on often low quality evidence from a small number of trials . Multimedia education about medications could therefore be considered as an adjunct to usual care but there is inadequate evidence to recommend it as a replacement for written education or education by a health professional . Multimedia education may be considered as an alternative to education provided by a health professional , particularly in setting s where provision of detailed education by a health professional is not feasible . More studies evaluating multimedia educational interventions are required in order to increase confidence in the estimate of effect of the intervention . Conclusions regarding the effect of multimedia education were limited by the lack of information provided by study authors about the educational interventions , and variability in their content and quality . Studies testing educational interventions should provide detailed information about the interventions and comparators . Research is required to establish a framework that is specific for the evaluation of the quality of multimedia educational programs . Conclusions were also limited by the heterogeneity in the outcomes reported and the instruments used to measure them . Research is required to identify a core set of outcomes which should be measured when evaluating patient educational interventions . Future research should use consistent , reliable and vali date d outcome measures so that comparisons can be made between studies 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 OBJECTIVE To determine whether a responsive parenting ( RP ) intervention affects infant dietary patterns . METHODS Primiparous mother-newborn dyads ( n = 291 ) were r and omized to the Intervention Nurses Start Infants Growing on Healthy Trajectories ( INSIGHT ) RP intervention or control . Curricula were delivered at nurse home visits at ages 3 , 16 , 28 , and 40 weeks . RP group feeding guidance advised responsive feeding , delayed introduction of solids , repeated exposure to novel foods , and age-appropriate portion sizes . Latent class analysis identified patterns of dietary exposure at 9 months . Class membership at 9 months was used to predict BMI percentile at 2 years . RESULTS Five dietary patterns were identified : " Breastfed , Fruits and Vegetables , " " Breastfed , Low Variety , " " Formula , Fruits and Vegetables , " " Formula , Low Variety , " and " Formula , High Energy Density . " Over 60 % of infants had patterns low in fruits and vegetables or high in energy-dense foods . RP group infants were less likely than control to be in the " Formula , Low Variety " class ( OR = 0.40 , 95 % CI 0.23 - 0.71 ) or " Formula , High Energy Density " class ( OR = 0.28 , 95 % CI 0.12 - 0.61 ) relative to the " Formula , Fruits and Vegetables " class . Dietary pattern at 9 months was significantly associated with BMI percentile at 2 years . CONCLUSIONS While a majority of infants consumed diets low in fruits and vegetables , the INSIGHT RP intervention was associated with healthier dietary patterns BACKGROUND Among young children in Burkina Faso , anemia and chronic and acute undernutrition are widespread . OBJECTIVE This study assessed the impact of Helen Keller International 's ( HKI ) 2-y integrated agriculture [ homestead food production ( HFP ) ] and nutrition and health behavior change communication ( BCC ) program , targeted to women , on children 's ( 3 - 12.9 mo old at baseline ) anthropometry ( stunting , wasting , and underweight ) , mean hemoglobin ( Hb ) , anemia ( Hb < 11 g/dL ) , and diarrhea prevalence . METHODS We used a cluster-r and omized controlled trial , with 55 villages r and omly assigned to a control group ( n = 25 ) or 1 of 2 treatment groups ( n = 15 each ) , which differed by who delivered the BCC messages [ older women leaders or health committee ( HC ) members ] . We used difference-in-difference ( DID ) estimates to assess impacts on child outcomes . RESULTS We found marginally significant ( P < 0.10 ) impacts on Hb ( DID : 0.51 g/dL ; P = 0.07 ) and wasting [ DID : -8.8 percentage point ( pp ) ; P = 0.08 ] and statistically significant ( P < 0.05 ) impacts on diarrhea ( -15.9 pp ; P = 0.00 ) in HC compared with control villages among children aged 3 - 12.9 mo and larger impacts for anemia ( DID : -14.6 pp ; P = 0.03 ) and mean Hb ( DID : 0.74 g/dL ; P = 0.03 ) among younger children ( aged 3 - 5.9 mo ) . However , we found no significant impacts on stunting or underweight prevalence . Plausibility was supported by greater improvements in women 's agricultural production and maternal infant and young child feeding and care knowledge and practice s in HC compared with control villages . CONCLUSIONS HKI 's 2-y integrated HFP+BCC program ( HC group ) significantly improved several child outcomes , including wasting ( marginal ) , diarrhea , Hb , and anemia , especially among the youngest children . This is the first cluster-r and omized controlled trial of an HFP program that documents statistically significant positive effects on these child nutrition outcomes . This trial was registered at clinical trials.gov as NCT01825226 Background HIV-awareness programs tailored toward the needs of rural communities are needed . We sought to quantify change in HIV knowledge in three rural Nigerian villages following an integrated culturally adapted and technology assisted educational intervention . Methods A prospect i ve 14-week cohort study was design ed to compare short-term changes in HIV knowledge between seminar-based education program and a novel program , which capitalized on the rural culture of small-group oral learning and was delivered by portable digital-audio technology . Results Participants were mostly Moslem ( 99 % ) , male ( 53.5 % ) , with no formal education ( 55 % ) . Baseline HIV knowledge was low ( < 80 % correct answers for 9 of the 10 questions ) . Knowledge gain was higher ( p < 0.0001 for 8 of 10 questions ) in the integrated culturally adapted and technology-facilitated ( n = 511 ) compared with the seminar-based ( n = 474 ) program . Conclusions Baseline HIV-awareness was low . Culturally adapted , technology-assisted HIV education program is a feasible cost-effective method of raising HIV awareness among low-literacy rural communities |
13,884 | 11,403,346 | The survey shows that change in blood pressure in indeed a poor indicator of change in resistance vessel structure .
However , it is a remarkably consistent finding that normalization of resistance vessel structure is obtained with therapeutic regimens which reduce blood pressure by vasodilation rather than by lowering cardiac output Thus , to the extent that normalization of resistance vessel structure is deemed a goal of antihypertensive treatment , the survey points towards the importance of considering not only the treatment effect on blood pressure , but also the haemodynamic effects within patients with essential hypertension | Correction of structural abnormalities in resistance arteries of patients with essential hypertension is a potential treatment goal , in addition to blood pressure reduction .
However , available evidence from human as well as from animal studies indicates that antihypertensive therapy is not always accompanied by normalization of resistance vessel structure , despite normalization of blood pressure .
Thus , blood pressure is not the only factor determining resistance vessel structure , and experimental studies show that several factors could play a role , including shear stress and hormonal stimulation .
To date , there has been no systematic review of the many published papers which have studied the structural effects of antihypertensive therapy , and it is not known which conditions are best able to normalize resistance vessel structure .
We have therefore made a survey of the available literature . | BACKGROUND Structural and functional alterations of the vasculature may contribute to complications of hypertension . Because angiotensin II may be pivotal in some of these vascular abnormalities , we tested the hypothesis that the angiotensin type 1 ( AT(1 ) ) receptor antagonist losartan , in contrast to the beta-blocker atenolol , would correct resistance artery abnormalities in patients with essential hypertension . METHODS AND RESULTS Nineteen untreated patients with mild essential hypertension ( 47+/-2 years , range 30 to 65 years ; 57 % male ) were r and omly assigned in double-blind fashion to losartan or atenolol treatment for 1 year . Nine age/sex-matched normotensive subjects were also studied . Both treatments reduced blood pressure to a comparable degree ( losartan , from 149+/-4.1/101+/-1.6 to 128+/-3.6/86+/-2.2 mm Hg , P<0.01 ; atenolol , from 150+/-4.0/99+/-1.2 to 130+/-3.2/84+/-1.4 mm Hg , P<0.01 ) . Resistance arteries ( luminal diameter 150 to 350 microm ) dissected from gluteal subcutaneous biopsies were studied on a pressurized myograph . After 1 year of treatment , the ratio of the media width to lumen diameter of arteries from losartan-treated patients was significantly reduced ( from 8.4+/-0.4 % to 6.7+/-0.3 % , P<0.01 ) . Arteries from atenolol-treated patients exhibited no significant change ( from 8 . 3+/-0.3 % to 8.8+/-0.5 % after treatment ) . Endothelium-dependent relaxation ( acetylcholine-induced ) was normalized by losartan ( from 82.1+/-4.9 % to 94.7+/-1.1 % , P<0.01 ) but not by atenolol ( from 80 . 4+/-2.7 % to 81.7+/-4.6 % ) . Endothelium-independent relaxation ( by sodium nitroprusside ) was unchanged after treatment . CONCLUSIONS The AT(1 ) antagonist losartan corrected the altered structure and endothelial dysfunction of resistance arteries from patients with essential hypertension , whereas the beta-blocker atenolol had no effect To investigate the time course of cardiovascular structural changes in patients with essential hypertension after angiotensin-converting enzyme ( ACE ) inhibition , we determined left ventricular structure , minimal vascular resistance in the forearm as an index of resistance vessel structure and stiffness beta of carotid artery in 15 essential hypertensive subjects during a placebo period and after 2 , 6 , and 12 months of temocapril treatment . Blood pressure decreased within 2 weeks , and the antihypertensive effects were noted throughout the 12-month administration period . Left ventricular mass index decreased significantly after 2 months ( 120+/-12 to 106+/-9 g/m2 ; p < 0.01 ) and was normalized after 12 months ( 88+/-6 g/m2 ) . Postischemic minimal vascular resistance in the forearm decreased gradually from 2.1+/-0.5 to 1.6+/-0.4 PRU at month 12 of temocapril treatment . In contrast , increased stiffness index beta of carotid artery was not altered during a 1-year treatment period ( 11.4+/-4.9 to 11.6+/-3.8 at month 12 of treatment ) . These data indicated that the regression of structural changes of left ventricle and arterioles occurred gradually and progressively for 1-year treatment with ACE inhibition , but large arteries were not affected Seventeen male untreated mild essential hypertensive patients aged 41 + /- 2 years agreed to participate in a double-blind r and omized trial to test the effects of antihypertensive treatment on the structure and function of subcutaneous resistance arteries . Patients were treated with either 50 to 100 mg/d atenolol or 2.5 to 5 mg/d cilazapril . Blood pressure before treatment was 148 + /- 6/99 + /- 1 and 147 + /- 2/99 + /- 1 mm Hg , respectively . At 1 year of treatment blood pressure was 131 + /- 4/85 + /- 2 and 132 + /- 2/87 + /- 1 mm Hg , respectively . Resistance arteries ( 200 to 400 microns lumen diameter ) dissected from subcutaneous gluteal biopsies obtained before treatment and at 1 year showed that the media-lumen ratio of arteries from patients treated with cilazapril was reduced to 6.31 + /- 0.21 % from 7.54 + /- 0.31 % before treatment ( P < .05 ) , still slightly but significantly larger ( P < .05 ) than the media-lumen ratio of resistance arteries of normotensive control subjects ( 5.15 + /- 0.30 % ) . In contrast , in arteries from patients treated with atenolol there was no significant change with treatment ( 7.97 + /- 0.60 % before and 8.07 + /- 0.45 % after 1 year of treatment ) . Active wall tension responses to endothelin-1 were blunted in hypertensive patients and normalized in the cilazapril-treated patients . Depressed active media stress responses to norepinephrine , arginine vasopressin , and endothelin-1 were accordingly normalized in the patients receiving cilazapril as the media width became thinner but were unchanged in those taking atenolol . ( ABSTRACT TRUNCATED AT 250 WORDS Our study attempted to evaluate the importance of changes in the circulating renin-angiotensin-aldosterone system ( RAAS ) and in hemodynamics in relation to observed changes in cardiovascular structure . We studied previously untreated men ( n = 28 ) with essential nonmalignant hypertension and a supine casual diastolic blood pressure > 95 mm Hg on three to four separate ( > 1-week interval ) occasions measured in triplicate . We used intraarterial blood pressure , dye-dilution technique , plethysmography ( h and s ) , eye-ground photos , M-mode echocardiography , radio immunoassays , and multiple regression analysis . Patients were r and omized to 6 months of double-blind treatment with either enalapril or hydrochlorothiazide , following 4 to 6 weeks on placebo . We found that enalapril blocked the plasma angiotensin converting enzyme ( ACE ) with a secondary increment in plasma renin activity ( PRA ) and reductions in angiotensin II ( AII ) and aldosterone . Blood pressure was lowered through a reduction in total peripheral resistance ( TPR ) . Hydrochlorothiazide increased PRA , AII , and aldosterone , and lowered blood pressure mainly through a reduction in cardiac output . Enalapril was significantly more effective than hydrochlorothiazide in reversing structural changes in the retinal and h and vasculature as well as in the heart . A reduction in cardiac hypertrophy was seen even in the occasional enalapril-treated patient , in whom little or no reduction in blood pressure occurred . In the stepwise regression analyses , the changes in retinal and h and vascular structure were most strongly related to various changes in the RAAS , explaining 15 to 34 % of the variance . For the changes in cardiac structure , the type of therapy ( enalapril or hydrochlorothiazide ) appeared to be the most important factor , explaining between 29 and 50 % of the variance . The changes in cardiac structure were even more strongly related to changes in the RAAS for the enalapril treated patients and explained up to 55 % of the variance in cardiac structure . It can be concluded that the reversal of structural vascular changes during antihypertensive therapy was more dependent on the blockade of the RAAS than on lowering of the blood pressure In a double-blind r and omized trial , the effects of treatment with an angiotensin-converting enzyme ( ACE ) inhibitor ( perindopril ) and a beta-blocker ( atenolol ) on small artery structure were compared in previously untreated essential hypertensive patients . Subjects ( diastolic blood pressure > or = 100 and < or = 120 mm Hg ) were r and omly assigned to treatment for 12 months with either perindopril ( n = 13 , 4 to 8 mg/d ) or atenolol ( n = 12 , 50 to 100 mg/d ) ; the dosage was adjusted upward and in some cases combined ( n = 5 , perindopril ; n = 2 , atenolol ) with thiazide diuretic to achieve target blood pressure ( diastolic blood pressure below 90 mm Hg ) . Before and at the end of treatment , gluteal biopsies were taken under local anesthetic ; from these biopsies , two small arteries were dissected and mounted on a myograph for morphometry . The reduction in blood pressure with atenolol ( drop in mean blood pressure 28.4 + /- 1.8 mm Hg ) was greater than with perindopril ( 20.6 + /- 1.8 mm Hg , P < .05 ) . Perindopril treatment caused an increase in small artery diameter ( 231 + /- 14 to 274 + /- 13 microns , P < .05 ) and a reduction in the ratio of media thickness to lumen diameter ( 7.94 + /- 0.65 % to 5.96 + /- 0.42 % , P < .05 ) , whereas atenolol had no effect ( 246 + /- 14 to 231 + /- 13 microns and 7.14 + /- 0.47 % to 6.79 + /- 0.45 % , respectively ) . The change in small artery morphology caused by perindopril was not accompanied by any change in media cross-sectional area , suggesting that the change was due to " remodeling . " ( ABSTRACT TRUNCATED AT 250 WORDS In order to investigate whether hypertension-related structural vascular changes may be influenced by antihypertensive treatment , 10 patients were studied suffering from essential arterial hypertension , five males and five females , aged between 34 and 61 years ( mean age : 46.9 + /- 8.13 years ) . All patients received a placebo for 1 week and then captopril , 75 mg b.i.d . for 3 months . After placebo and captopril treatments , the following parameters were evaluated : SBP , DBP , mean blood pressure ( MBP ) , by the formula 1/3 ( SBP + 2 x DBP ) and basal and minimal vascular resistances , respectively obtained by the ratios MBP/rest flow and MBP/peak flow . Blood flows have been obtained by strain gauge plethysmography . A significant decrease in systolic ( P less than 0.025 ) , diastolic ( P less than 0.01 ) and mean blood pressure ( P less than 0.01 ) , basal vascular resistances ( 52 + /- 19 vs 28 + /- 12 A.U. , P less than 0.01 ) and minimal vascular resistances ( 6.3 + /- 2.2 vs 3.9 + /- 2.8 A.U. , P less than 0.025 ) has been observed after captopril treatment in comparison to placebo , whereas rest ( 2.9 + /- 0.7 vs 4.1 + /- 0.9 ml.min-1.100 g-1 , P less than 0.01 ) and peak blood flows ( 21.3 + /- 5.8 vs 29.7 + /- 9.4 ml.min-1.100 g-1 ) significantly increased . These data seem to indicate that antihypertensive treatment with the angiotensin-converting enzyme inhibitor , captopril , is not only efficacious in inducing a significant blood pressure decrease , consequent to the reduction of basal vascular resistance ( due to the vasodilating effects of the drug ) , but is also able to reduce minimal vascular resistance . ( ABSTRACT TRUNCATED AT 250 WORDS We studied the structural and functional characteristics of the vascular bed at calf level in 46 middle aged hypertensive patients ( 20 males and 26 females ) treated with different beta-blockers . After one week of placebo , the patients were divided into three groups : group 1 was treated with labetalol , an alpha-beta-blocker ( 200 mg t.t.d . ) ; group 2 was treated with acebutolol , a cardioselective beta-blocker with intrinsic sympathomimetic activity ( ISA ) ( 200 mg t.t.d . ) ; group 2 was treated with acebutolol , a cardioselective beta-blocker with intrinsic sympathomimetic activity ( ISA ) ( 200 mg t.t.d . ) ; group 3 was treated with metoprolol , a cardioselective beta-blocker without ISA ( 100 mg t.t.d . ) . Before and after placebo , and after three months of active drug treatment , we measured blood pressure , and rest and peak flow at the calf level by strain gauge plethysmography . Basal and minimal vascular resistances were calculated as the ratio between mean blood pressure and rest or peak flow , respectively . A significant decrease in blood pressure was observed in each group . However , basal and minimal vascular resistances decreased only in the labetalol-treated group . These observations indicate that antihypertensive agents that have similar effects on blood pressure , may have different effects on minimal vascular resistance . Therefore , maximum vasodilation of arterioles improves , suggesting that long term treatment with labetalol , but not with other beta-blockers is able to induce a partial regression of vascular structural alterations in hypertensive patients OBJECTIVES To assess the peripheral and central haemodynamics , in particular the effect on minimal resistance in the h and , with an ACE inhibitor in comparison with a diuretic . DESIGN Double-blind r and omized parallel group study . SUBJECTS Twenty-eight previously untreated men with essential hypertension ( supine diastolic blood pressure > 95 mmHg repeatedly on placebo ) . METHODS /INTERVENTION : Causal and intra-arterial blood pressure , dye-dilution technique , water plethysmography at rest and at ischaemia , enalapril ( n = 14 ) , hydrochlorothiazide ( n = 14 ) . RESULTS After 6 months the mean arterial pressure was reduced from 112.7 to 96.9 mmHg ( change -15.9 mmHg ; 95 % confidence interval ( CI ) -21.9 , -9.8 ) on enalapril and from 110.1 to 101.5 mmHg ( change -8.6 mmHg ; CI -14.4 , -2.8 ) . Heart rate did not change on any of the therapies . Enalapril reduced blood pressure mainly through a reduction in total peripheral resistance ( delta -3.0 PRU100 ; CI -5.6 , -0.4 ) while hydrochlorothiazide reduced blood pressure mainly through a reduction in cardiac output ( delta -0.8 l/min-1 ; CI -1.5 , -0.07 ) . Minimal vascular resistance ( mean of right and left h and ) displayed a significant time x treatment interaction indicating a different trend with enalapril than hydrochlorothiazide with a change of -0.12 PRU100 ( CI -0.33 , 0.05 ) on enalapril and a change of 0.14 ( CI -0.29 , 0.56 ) on hydrochlorothiazide . The resistance level after 6 months was significantly higher on hydrochlorothiazide than on enalapril ( P = 0.0105 ) . CONCLUSION Enalapril reduced blood pressure through vasodilatation and hydrochlorothiazide through decreased cardiac output . The two therapies also affected minimal vascular resistance ( an indirect measure of vascular wall thickness ) differently ; with enalapril showing a favourable response in contrast to hydrochlorothiazide Untreated essential hypertension is associated with left ventricular hypertrophy ( LVH ) and structural changes in resistance vessels . The aim of this study was to establish the effect of perindopril based antihypertensive therapy on media thickness to lumen diameter ( media : lumen ) ratio of peripheral resistance vessels and left ventricular mass in essential hypertension . Twenty-five patients with newly diagnosed or poorly regulated essential hypertension were treated with perindopril . Insufficient treatment response ( DBP > 90 mmHg ) led to addition of isradipine , and hydralazine was used as a tertiary drug if necessary . Gluteal subcutaneous biopsies were taken surgically at baseline and after 9 months of successful treatment . Two small resistance arteries were isolated and mounted in a small vessel myograph , and media : lumen ratio ( % ) was measured under st and ardized conditions . Left ventricular mass was determined by echocardiography . Mean ( SD ) media : lumen ratio decreased from 9.8 ( 2.6 ) % to 7.8 ( 1.9 ) % ( p < 0.05 ) , while left ventricular mass decreased from 299 ( 75 ) g to 199 ( 53 ) g ( p < 0.001 ) . Correlation was found between changes in left ventricular mass index and media : lumen ratio ( r = 0.62 , p < 0.01 ) . It is concluded that a perindopril based regimen efficiently normalizes resistance artery structure and left ventricular hypertrophy in essential hypertension within one year of treatment . The impact of these findings on the excess cardiovascular morbidity and mortality in arterial hypertension remains to be investigated OBJECTIVE : To examine the relation between endothelial dependent and endothelial independent stimuli of varying intensity and measures of vascular function in the brachial artery of young healthy adults , to determine whether these responses are consistent and can be used to assess endothelial function . DESIGN AND SETTING : High resolution ultrasound was used to measure brachial artery diameter at rest , after reactive hyperaemia induced by forearm cuff occlusion , and after sublingual isosorbide dinitrate ( ISDN ) . Each subject was assigned to a r and om order of six cuff occlusion times ( 30 seconds , 1.5 , 2.5 , 3.5 , 4.5 , and 8 minutes ) and six doses of ISDN ( 10 , 20 , 50 , 100 , 200 , and 400 micrograms ) . SUBJECTS : Three males and three females mean age 31 years ( range 25 to 43 ) with no known risk factors for cardiovascular disease . MAIN OUTCOME MEASURES : Flow mediated , endothelial dependent dilatation was compared to duration of cuff occlusion , peak reactive hyperaemia , and duration of increased flow . Nitrate induced , endothelial independent dilatation was compared to dose of ISDN and change in flow . RESULTS : Vessel dilatation and duration of peak flow change increased with longer duration of cuff occlusion . After 4.5 minutes of occlusion , flow mediated dilatation was mean ( SD ) 96 (6)% of maximal response and did not increase significantly with longer occlusion times . No significant dilatation occurred after 10 or 20 micrograms of ISDN in any subject . With increasing doses up to 200 micrograms there was an increase in dilatation . Endothelial independent dilatation did not increase significantly with doses of ISDN above 200 micrograms . CONCLUSIONS : Measures of arterial function vary with duration of blood flow occlusion and ISDN dose . Maximum arterial response was reached in all subjects after 4.5 minutes of blood flow occlusion or 200 micrograms of ISDN . Therefore , these variables produce consistent reproducible measures of endothelial function Although it has been recognized that enalapril lowers blood pressure by reducing the total peripheral vascular resistance , its direct effect on blood vessels is largely unknown . Little information is available about the influence of enalapril on the different vascular regions . Ten patients with moderate essential hypertension were treated with enalapril 20 mg daily in a double-blind , placebo controlled cross-over study for six weeks during each period . Blood pressure and heart rate were measured in supine , sitting and st and ing position . Venous capacity was derived from pressure volume curves plotted simultaneously at forearm and calf . Arterial blood flow at rest and during reactive hyperemia was measured at calf and finger by plethysmography . Enalapril increases venous capacity in upper and lower limbs in patients with moderate essential hypertension . Also , there is vasodilation of calf and finger arteries both at rest and during reactive hyperemia . Finger and calf arteries contribute to the decrease of the total peripheral vascular resistance during treatment with enalapril ; thus , ACE inhibition is capable of correcting the increased peripheral resistance which often is the main cause of arterial hypertension Objective To investigate the effects of angiotensin converting enzyme inhibition on the structure of resistive arteries assessed from minimal vascular resistance in the forearm and the calf and on left ventricular mass index of elderly hypertensive subjects with left ventricular hypertrophy . Design and methods We evaluated 23 elderly patients [ 12 women and 11 men , aged 70 ± 1 years ( mean ± SEM ) ] with essential hypertension assessed with ambulatory blood pressure monitoring and left ventricular hypertrophy before and at the end of 6 months ' treatment with quinapril . Minimal vascular resistance was calculated as the ratio of mean arterial pressure to regional blood flow measured upon restoration of circulation after 13 min of ischaemia combined with exercise and taken as an index of resistive vessel structure ( i.e. media : lumen ratio ) . Results Daytime ambulatory blood pressure had decreased from 164 ± 2/95 ± 1 to 147 ± 3/86 ± 2 mmHg ( P < 0.001 ) and left ventricular mass index decreased from 138 ± 4 to 120 ± 5 g/m2 ( P < 0.001 ) at the end of treatment . Minimal vascular resistance in the forearm had decreased from 3.1 ± 0.3 to 2.4 ± 0.2 mmHg/ml per 100 ml per min ( P < 0.01 ) whereas we observed no change in minimal vascular resistance in the calf after treatment ( 4.6 ± 0.7 versus 4.2 ± 0.4 mmHg/ml per 100 ml per min , NS ) . The decrease in minimal vascular resistance in the forearm was correlated significantly to the fall in 24 h ambulatory mean arterial pressure ( r = 0.58 , P < 0.01 ) . Changes in left ventricular mass index were not correlated to those in ambulatory blood pressure or to those in minimal vascular resistance in the forearm . Conclusions A 6-month reduction in blood pressure under quinapril treatment was associated with decreases in left ventricular hypertrophy and in minimal vascular resistance in the forearm of elderly hypertensive patients . Absence of structural changes in leg vasculature could be related to the greater arterial pressure prevalent in the lower limbs while patients stood upright and , consequently , a proportionately smaller decrease in blood pressure , as well as greater structural changes and fibrous damage than those of the upper limbs . J Hypertens 16:673–679 © 1998 Lippincott-Raven Publishers In a double-blind , comparative study metoprolol ( 100 to 300 mg/day ) or pindolol ( 5 to 15 mg/day ) was given in r and omized order to 39 patients with uncomplicated essential hypertension . Peripheral hemodynamics were studied by noninvasive means after an initial 6-week placebo period and again after 6 weeks and 6 months of active treatment . Three patients withdrew from the trial during the 6-week period of active treatment . Heart rate during exercise on an ergometric bicycle to a predetermined workload indicated that the degree of beta-adrenoceptor blockade was identical during treatment with either metoprolol or pindolol . Both agents also reduced resting blood pressure to the same extent . Heart rate at rest fell considerably more during metoprolol than pindolol therapy , while vascular resistance was reduced by pindolol but not by metoprolol . This indicates that the antihypertensive effect of metoprolol can be ascribed mainly to cardiac mechanisms ; in contrast , pindolol appears to lower blood pressure primarily through vascular effects . Studies at maximal dilatation showed that pindolol , but not metoprolol , reduced resistance at maximal dilatation after 6 months of treatment , indicating that a reversal of the structural vascular changes had occurred . The hemodynamic differences between the 2 agents can probably be explained by the fact that pindolol with its intrinsic sympathomimetic activity acts as a partial agonist causing active stimulation of vascular beta 2 adrenoceptors and relaxation of resistance vessels The objective of this study was to assess the regression of vascular structural changes seen in essential hypertension after long-term monotherapy with a calcium antagonist and to clarify the relations to cytosolic free calcium and neurohumoral factors . Blood pressure , minimal vascular resistance ( MVR ) by strain-gauge plethysmography , cytosolic free calcium in platelets ( [Ca2+]i ) by Quin 2 method , plasma renin activity ( PRA ) and plasma aldosterone concentration ( PAC ) , plasma noradrenaline ( PNA ) and parathyroid hormone ( PTH ) were measured in 14 essential hypertensives during a placebo period and 2 and 6 months after anti-hypertensive treatment with nilvadipine . Blood pressure decreased from 174 + /- 10/104 + /- 8 mm Hg during the placebo period to 154 + /- 13/93 + /- 14 mm Hg 2 weeks after nilvadipine , and the hypotensive effects were found throughout the 6-month period . Although increased MVR seen in hypertensives did not change after 2 months ( from 2.1 + /- 0.7 to 1.9 + /- 0.6 mm Hg/ml/min per 100 ml tissue ( PRU ) , NS ) , MVR decreased significantly at 6 months ( 1.6 + /- 0.4 , PRU , P < 0.05 ) . Elevated [Ca2+]i seen in hypertensives during the placebo period decreased significantly 2 months after nilvadipine treatment ( 156 + /- 26 and 140 + /- 27 nM , P < 0.01 ) . The changes in MVR were associated with those in [Ca2+]i 6 months after nilvadipine ( r = 0.56 , P < 0.05 ) . However , the changes in MVR did not correlate with those in PRA , PAC , PNA or PTH . ( ABSTRACT TRUNCATED AT 250 WORDS A Laser-Doppler flowmeter was used to investigate the effect of essential hypertension on blood flow in maximally vasodilated skin , heated to 44 degrees C. Maximum Laser-Doppler flux ( MLDF ) was measured in 12 subjects with essential hypertension on no treatment and in 12 normotensive control subjects , and the resistance to flow was estimated by dividing pressure by flux . MLDF was not significantly different in the two groups : 3.69 + /- 0.87 V ( arbitrary units , subjects with hypertension , mean + /- S.D. ) vs 3.48 + /- 1.29 V ( normotensive control subjects ) , despite the higher mean arterial pressure in the hypertensive group : 128.9 + /- 16.3 mmHg vs 91.8 + /- 9.1 mmHg ( p less than 0.01 ) . Resistance to flow was elevated in the subjects with hypertension : 37.2 + /- 12.8 mmHg/V vs. 29.6 + /- 10.4 ( p = 0.05 ) , and in the hypertensive group resistance was significantly correlated with mean arterial pressure ( r = 0.69 , n = 12 , less than 0.025 ) . Following two weeks vasodilator treatment in 6 of the hypertensive subjects , MLDF and mean arterial pressure fell , but the resistance remained elevated . These findings confirm the presence of a structurally-based increase in flow-resistance in the skin in subjects with hypertension , which prevents overperfusion of this tissue in the face of increased arterial pressure . The simple and noninvasive technique described herein could be used on a large scale to prospect ively evaluate the reversibility ( or otherwise ) of structural resistance changes with pharmacological antihypertensive therapy Hypertension is associated with an altered design of resistance vessels and decreased endothelium-dependent vasodilator response to acetylcholine . A role of angiotensin II in both defects is suggested by animal experiments in which angiotensin-converting enzyme inhibition reverted structural and functional changes . We investigated the effects of 20 weeks of therapy with the angiotensin-converting enzyme inhibitor cilazapril ( 5 mg twice daily ) on the endothelium-dependent response to brachial artery infusions of acetylcholine and the endothelium-independent vascular relaxation after sodium nitroprusside in 22 subjects with mild to moderate essential hypertension . In addition , we measured minimal forearm vascular resistance ( ratio of mean arterial pressure and forearm blood flow after heating , ischemia , and ischemic exercise ) as an indirect estimate of vascular structure . Cilazapril decreased blood pressure ( 151 + /- 14/99 + /- 7 mm Hg during placebo to 138 + /- 17/89 + /- 8 mm Hg after cilazapril treatment , P<.01 ) and baseline ( 42.2 + /- 12.6 to 37.1 + /- 10.6 U , P<.05 ) and minimal ( 3.0 + /- 1.1 to 2.4 + /- 0.7 U , 15.9 + /- 20.2 % ; P<.05 ) forearm vascular resistances . The change in minimal forearm vascular resistance was unrelated to age , duration of hypertension , or changes in blood pressure . Sodium nitroprusside increased forearm blood flow from 2.6 + /- 1.0 to 11.4 + /- 5.9 mL/min per 100 mL and acetylcholine to 21.5 + /- 17.8 . Both responses did not change after cilazapril . The data provide indirect evidence that cilazapril therapy may improve vascular structure in human hypertension . The lack of relationship between vascular and blood pressure changes would be compatible with experimental evidence supporting a role for angiotensin II in the development and regression of vascular changes , but this needs further study . Therapy with cilazapril for 20 weeks , like other antihypertensive therapy , does not seem to influence endothelial vasodilator function in humans to a significant degree |
13,885 | 25,082,388 | Conclusions Evidence from the present systematic review suggests that the majority of the available treatments represent either cost-saving or cost-effective options for NSTE-ACS patients . | Background Acute coronary syndrome ( ACS ) represents the most common subset of cardiovascular heart diseases and relates to high rates of morbidity and mortality worldwide and , consequently , to both the direct and indirect costs to the health system and society .
Given the rising healthcare costs combined with budgetary constraints , health care systems and decision makers are faced with challenging decisions and the need to choose alternative treatments that not only improve patient quantity and quality of life but are also economically attractive .
Objectives To systematic ally review the published literature and to identify studies evaluating the cost effectiveness of different treatments for patients presenting with non-ST-segment elevation ( NSTE ) ACS . | BACKGROUND In the ESSENCE trial , subcutaneous low-molecular-weight heparin ( enoxaparin ) reduced the 30-day incidence of death , myocardial infa rct ion , and recurrent angina relative to intravenous unfractionated heparin in 3171 patients with acute coronary syndrome ( unstable angina or non-Q-wave myocardial infa rct ion ) . No increase in major bleeding was seen . METHODS AND RESULTS Of the 936 ESSENCE patients r and omized in the United States , 655 had hospital billing data collected . For the remainder , hospital costs were imputed with a multivariable linear regression model ( R2=.86 ) . Physician fees were estimated from the Medicare Fee Schedule . During the initial hospitalization , major re source use was reduced for enoxaparin patients , with the largest effect seen with coronary angioplasty ( 15 % versus 20 % for heparin , P=.04 ) . At 30 days , these effects persisted , with the largest reductions seen in diagnostic catheterization ( 57 % versus 63 % for heparin , P=.04 ) and coronary angioplasty ( 18 % versus 22 % , P=.08 ) . All re source use trends seen in the US cohort were also evident in the overall ESSENCE study population . In the United States , the mean cost of a course of enoxaparin therapy was $ 155 , whereas that for heparin was $ 80 . The total medical costs ( hospital , physician , drug ) for the initial hospitalization were $ 11 857 for enoxaparin and $ 12620 for heparin , a cost advantage for the enoxaparin arm of $ 763 ( P=.18 ) . At the end of 30 days , the cumulative cost savings associated with enoxaparin was $ 1172 ( P=.04 ) . In 200 bootstrap sample s of the 30-day data , 94 % of the sample s showed a cost advantage for enoxaparin . CONCLUSIONS In patients with acute coronary syndrome , low-molecular-weight heparin ( enoxaparin ) both improves important clinical outcomes and saves money relative to therapy with st and ard unfractionated heparin BACKGROUND Despite the use of aspirin , there is still a risk of ischaemic events after percutaneous coronary intervention ( PCI ) . We aim ed to find out whether , in addition to aspirin , pretreatment with clopidogrel followed by long-term therapy after PCI is superior to a strategy of no pretreatment and short-term therapy for only 4 weeks after PCI . METHODS 2658 patients with non-ST-elevation acute coronary syndrome undergoing PCI in the CURE study had been r and omly assigned double-blind treatment with clopidogrel ( n=1313 ) or placebo ( n=1345 ) . Patients were pretreated with aspirin and study drug for a median of 6 days before PCI during the initial hospital admission , and for a median of 10 days overall . After PCI , most patients ( > 80 % ) in both groups received open-label thienopyridine for about 4 weeks , after which study drug was restarted for a mean of 8 months . The primary endpoint was a composite of cardiovascular death , myocardial infa rct ion , or urgent target-vessel revascularisation within 30 days of PCI . The main analysis was by intention to treat . FINDINGS There were no drop-outs . 59 ( 4.5 % ) patients in the clopidogrel group had the primary endpoint , compared with 86 ( 6.4 % ) in the placebo group ( relative risk 0.70 [ 95 % CI 0.50 - 0.97 ] , p=0.03 ) . Long-term administration of clopidogrel after PCI was associated with a lower rate of cardiovascular death , myocardial infa rct ion , or any revascularisation ( p=0.03 ) , and of cardiovascular death or myocardial infa rct ion ( p=0.047 ) . Overall ( including events before and after PCI ) there was a 31 % reduction cardiovascular death or myocardial infa rct ion ( p=0.002 ) . There was less use of glycoprotein IIb/IIIa inhibitor in the clopidogrel group ( p=0.001 ) . At follow-up , there was no significant difference in major bleeding between the groups ( p=0.64 ) . INTERPRETATION In patients with acute coronary syndrome receiving aspirin , a strategy of clopidogrel pretreatment followed by long-term therapy is beneficial in reducing major cardiovascular events , compared with placebo OBJECTIVES The aim of this study was to determine the economic impact of several anticoagulation strategies for moderate- and high-risk non-ST-segment elevation acute coronary syndrome ( NSTE-ACS ) patients managed invasively . BACKGROUND The ACUITY ( Acute Catheterization and Urgent Intervention Triage Strategy ) trial demonstrated that bivalirudin monotherapy yields similar rates of ischemic complications and less bleeding than regimens incorporating glycoprotein IIb/IIIa receptor inhibitors ( GPI ) for moderate- and high-risk NSTE-ACS . METHODS In ACUITY , 7,851 U.S. patients were r and omized to : 1 ) heparin ( unfractionated or enoxaparin ) + GPI ; 2 ) bivalirudin + GPI ; or 3 ) bivalirudin monotherapy . Patients assigned to GPI were also r and omized to upstream GPI before catheterization or selective GPI only with percutaneous coronary intervention . Re source use data were collected prospect ively through 30-day follow-up . Costs were estimated with st and ard methods including re source -based accounting , hospital billing data , and the Medicare fee schedule . RESULTS At 30 days , ischemic events were similar for all groups . Major bleeding was reduced with bivalirudin monotherapy compared with heparin + GPI or bivalirudin + GPI ( p < 0.001 ) . Length of stay was lowest with bivalirudin monotherapy or bivalirudin + catheterization laboratory GPI ( p = 0.02 ) . Despite higher drug costs , aggregate hospital stay costs were lowest with bivalirudin monotherapy ( mean difference range : $ 184 to $ 1,081 , p < 0.001 for overall comparison ) and at 30 days ( mean difference range : $ 123 to $ 938 , p = 0.005 ) . Regression modeling demonstrated that hospital savings were primarily due to less major and minor bleeding with bivalirudin ( $ 8,658/event and $ 2,282/event , respectively ) . CONCLUSIONS Among U.S. patients in the ACUITY trial , bivalirudin monotherapy compared with heparin + GPI result ed in similar protection from ischemic events , reduced bleeding , and shorter length of stay . Despite higher drug costs , aggregate hospital and 30-day costs were lowest with bivalirudin monotherapy . Thus bivalirudin monotherapy seems to be an economically attractive alternative to heparin + GPI for patients with moderate- and high-risk NSTE-ACS . ( Comparison of Angiomax Versus Heparin in Acute Coronary Syndromes [ ACS ] ; NCT00093158 ) Background The CURE study demonstrated that clopidogrel prevents a range of ischaemic cardiovascular events in patients with Acute Coronary Syndromes ( unstable angina or non-ST-segment elevation MI ) . Design We undertook an economic analysis of the use of clopidogrel in the UK , USA , Sweden , France and Canada based on the CURE study . Methods The costs of hospitalization , study drug and other medications were calculated , based on re source utilization for all patients in CURE . Unit costs were obtained for all re source items for each country , and are reported in local currencies in 2001 prices . Results While hospitalization costs were lower in the clopidogrel group , when the acquisition cost of clopidogrel for 9 months is included , the average cost per patient is higher in the clopidogrel group than the placebo group in all countries [ difference in costs ( with 95 % CI ) UK £ 208 ( 119 , 297 ) , US$ 451 ( 58 , 845 ) , SKr 2571 ( 728 , 4412 ) , Fr ∊325 ( 85 , 565 ) , C$ 161 ( −185 , 506 ) ] . The absolute reduction in the number of total primary events was 2.0 % , result ing in an incremental cost-effectiveness ratio ( ICER ) of £ 10,366 in the UK , $ 22,484 in the USA , SKr 127,951 in Sweden , ∊16,186 in France , and C$ 7973 in Canada per primary event avoided with clopidogrel . Conclusions Clopidogrel in CURE reduced hospitalization costs but the acquisition cost of clopidogrel creates an overall increase in direct health care costs over 9 months . Nevertheless , the cost-effectiveness is in a range comparable to other therapies currently utilized for acute coronary syndromes BACKGROUND In the PURSUIT trial , eptifibatide significantly reduced the 30-day incidence of death and myocardial infa rct ion relative to placebo in 9461 patients with an acute coronary syndrome ( unstable angina or non-Q-wave myocardial infa rct ion ) . METHODS AND RESULTS We conducted a 2-part prospect i ve economic sub study of the 3522 US patients enrolled in PURSUIT : ( 1 ) an empirical intention-to-treat comparison of medical costs ( hospital plus physician ) up to 6 months after hospitalization and ( 2 ) a lifetime cost-effectiveness analysis . The base-case cost-effectiveness ratio was expressed as the 1996 US dollars required to add 1 life-year with eptifibatide therapy . The 2 treatment arms had equivalent re source consumption and medical costs ( exclusive of the cost of the eptifibatide regimen ) during the index ( enrollment ) hospitalization ( P=0.78 ) and up to 6 months afterward ( P=0.60 ) . The average wholesale price of the eptifibatide regimen was $ 1217 , but a typical hospital discounted price was $ 1014 . The estimated life expectancy from r and omization in the US patients was 15.96 years for eptifibatide and 15.85 years for placebo , an incremental difference of 0.111 . The incremental cost-effectiveness ratio for eptifibatide therapy in US PURSUIT patients was $ 16 491 per year of life saved . This result was robust through a wide range of sensitivity analyses . The cost-utility ratio for eptifibatide ( using time trade-off defined utilities ) was $ 19 693 per added quality -adjusted life-year . CONCLUSIONS Based on the results observed in the US PURSUIT patients , the routine addition of eptifibatide to st and ard care for non-ST-elevation acute coronary syndrome patients is economically attractive by conventional st and ards AIMS To assess the direct medical costs and cost effectiveness of routine eptifibatide use amongst patients with unstable angina and myocardial infa rct ion without persistent ST-segment elevation in the Western European subgroup of the PURSUIT trial . METHODS AND RESULTS Health care re sources were collected for the Western European PURSUIT trial patients ( n=3697 ) . Unit costs for major re sources were developed within six countries using a consistent bottom-up methodology . Re source consumption from the Western European population was used to calculate the average direct medical costs per patient in the eptifibatide and placebo arms of the trial . Eptifibatide was estimated to cost 524 Euros per treatment . Long-term survival estimated from the 6-month trial survival data and combined with the cost data was used to calculate cost-effectiveness ratios . Additionally , cost per death and non-fatal myocardial infa rct ion at 30 days was calculated . Sensitivity analyses were conducted on the discount rate and re source consumption . Cost-effectiveness ratios ranged from 9603 Euros to 18 115 Euros per year of life saved with 3 % discount . Using re source consumption based on countries with low coronary arteriography rates , the cost per year of life saved was between 3329 Euros and 10 079 Euros . Using re source consumption based on high coronary arteriography rate countries , the cost per year of life saved was between 17 089 Euros and 24 099 Euros . Assuming no difference in treatment costs except for the addition of eptifibatide , the incremental cost per year of life saved was 23 818 Euros . CONCLUSIONS Routine eptifibatide use was associated with a reduction in the combined end-point of death and myocardial infa rct ion at 30 days , which was sustained at 6 months . Long-term projections indicate a modest increase in survival in eptifibatide patients . These data translate into cost-effectiveness ratios that compare favourably with other new technologies that are currently in use BACKGROUND Dual-antiplatelet therapy with aspirin and a thienopyridine is a cornerstone of treatment to prevent thrombotic complications of acute coronary syndromes and percutaneous coronary intervention . METHODS To compare prasugrel , a new thienopyridine , with clopidogrel , we r and omly assigned 13,608 patients with moderate-to-high-risk acute coronary syndromes with scheduled percutaneous coronary intervention to receive prasugrel ( a 60-mg loading dose and a 10-mg daily maintenance dose ) or clopidogrel ( a 300-mg loading dose and a 75-mg daily maintenance dose ) , for 6 to 15 months . The primary efficacy end point was death from cardiovascular causes , nonfatal myocardial infa rct ion , or nonfatal stroke . The key safety end point was major bleeding . RESULTS The primary efficacy end point occurred in 12.1 % of patients receiving clopidogrel and 9.9 % of patients receiving prasugrel ( hazard ratio for prasugrel vs. clopidogrel , 0.81 ; 95 % confidence interval [ CI ] , 0.73 to 0.90 ; P<0.001 ) . We also found significant reductions in the prasugrel group in the rates of myocardial infa rct ion ( 9.7 % for clopidogrel vs. 7.4 % for prasugrel ; P<0.001 ) , urgent target-vessel revascularization ( 3.7 % vs. 2.5 % ; P<0.001 ) , and stent thrombosis ( 2.4 % vs. 1.1 % ; P<0.001 ) . Major bleeding was observed in 2.4 % of patients receiving prasugrel and in 1.8 % of patients receiving clopidogrel ( hazard ratio , 1.32 ; 95 % CI , 1.03 to 1.68 ; P=0.03 ) . Also greater in the prasugrel group was the rate of life-threatening bleeding ( 1.4 % vs. 0.9 % ; P=0.01 ) , including nonfatal bleeding ( 1.1 % vs. 0.9 % ; hazard ratio , 1.25 ; P=0.23 ) and fatal bleeding ( 0.4 % vs. 0.1 % ; P=0.002 ) . CONCLUSIONS In patients with acute coronary syndromes with scheduled percutaneous coronary intervention , prasugrel therapy was associated with significantly reduced rates of ischemic events , including stent thrombosis , but with an increased risk of major bleeding , including fatal bleeding . Overall mortality did not differ significantly between treatment groups . ( Clinical Trials.gov number , NCT00097591 [ Clinical Trials.gov ] . OBJECTIVES We sought to evaluate the long-term cost-effectiveness of clopidogrel for up to one year after an acute coronary syndrome ( ACS ) without ST-segment elevation . BACKGROUND The efficacy of platelet inhibition with clopidogrel for up to one year after ACS was demonstrated in the Clopidogrel in Unstable angina to prevent Recurrent Events ( CURE ) trial , a r and omized trial of 12,562 patients in 28 countries that was conducted between 1998 and 2000 . Patients were given clopidogrel ( 300-mg load followed by 75 mg/day ) versus placebo , both in addition to aspirin , for a mean of nine months . METHODS We used patient-level clinical outcomes and re source use from the CURE trial and estimates of life expectancy gains as a result of the prevention of the clinical events of death , stroke , and myocardial infa rct ion on the basis of data from external sources . RESULTS Excluding clopidogrel costs , average costs of hospitalizations alone were 325 dollars less for the clopidogrel arm ( 95 % confidence interval -722 dollars to 45 dollars ) using diagnosis-related group-based Medicare reimbursement rates . When including clopidogrel costs ( 766 dollars greater for the clopidogrel arm ) , average total costs were 442 dollars higher for the clopidogrel arm ( 95 % confidence interval 62 dollars to 820 dollars ) . The incremental cost-effectiveness ratio ( ICER ) on the basis of the Framingham Heart Study was 6,318 dollars per life-year gained ( LYG ) with clopidogrel , with 94 % of bootstrap-derived ICER estimates < 50,000 dollars/LYG ; based on Saskatchewan , the ICER was 6,475 dollars/LYG with 98 % of estimates < 50,000 dollars . CONCLUSIONS Platelet inhibition with clopidogrel in patients for up to one year after presentation with an acute coronary syndrome is both effective and cost-effective OBJECTIVE To assess the long-term cost effectiveness of 1 year 's treatment with clopidogrel on top of st and ard therapy ( including aspirin ; ASA ) compared with st and ard therapy alone , in patients diagnosed with non-ST-segment-elevation acute coronary syndromes ( ACS ) in the UK . DESIGN Cost utility analysis using a Markov model , incorporating clinical data from CURE ( a multicentre r and omised controlled trial , involving 12,562 patients ) and data from UK observational studies . SETTING Health economic evaluation carried out from the perspective of the UK NHS . PATIENTS A representative cohort of 1000 UK patients aged 66 years , diagnosed with non-ST-segment-elevation ACS . INTERVENTIONS Either a combination of 75 mg/day clopidogrel ( 300 mg loading dose , within 24 h prior to hospital admission ) and st and ard therapy ( including ASA , 75 - 325 mg/day ) for 1 year followed by st and ard therapy alone for their remaining lifetime , or st and ard therapy alone ( including ASA , 75 - 325 mg/day ) for life . MAIN OUTCOME MEASURES Incremental cost per life-year gained and incremental cost per quality -adjusted life-year ( QALY ) gained . RESULTS In the base case , the incremental cost effectiveness of the clopidogrel combination vs st and ard therapy alone is estimated as pounds 6991 per life-year gained and pounds 7365 per QALY gained . The probability that clopidogrel remains cost effective within the generally accepted pounds 30,000 per QALY threshold is more than 80 % . The confidence interval around the relative risk for vascular death was identified as the main parameter affecting the estimated cost effectiveness . CONCLUSIONS One year 's treatment with clopidogrel is a cost effective intervention compared with st and ard therapy that should be considered as a routine treatment for patients with non-ST-segment-elevation ACS OBJECTIVE To determine the cost effectiveness of enoxaparin therapy versus unfractionated heparin ( UFH ) therapy for patients with unstable coronary artery disease from the perspective of a Canadian hospital . DESIGN A predictive decision analysis model using published clinical and economic evaluations and costs of medical care in Canada . PATIENTS A hypothetical cohort of patients presenting to hospital with unstable angina or non-Q-wave myocardial infa rct ion as defined by the Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-Wave Coronary Events ( ESSENCE ) trial . INTERVENTIONS Two antithrombotic treatment strategies were compared : ( i ) enoxaparin 1 mg/kg subcutaneously every 12 hours , and ( ii ) UFH intravenous bolus and constant infusion adjusted to maintain a therapeutic activated partial thromboplastin time . Both treatment strategies included 100 to 325 mg of oral aspirin daily . Enoxaparin or UFH was continued for a minimum of 48 hours to a maximum of 8 days . Cumulative outcomes were considered up to 30 days after initial presentation to hospital . RESULTS At 30 days , 19.8 % of patients who received enoxaparin compared with 23.3 % of patients who received UFH reached one of the primary composite events . There was no difference in major bleeding between the 2 treatment groups ( 6.5 % enoxaparin vs 6.8 % UFH ) . The average total direct medical cost per patient was $ Can848 with the enoxaparin strategy versus $ Can892 with the UFH strategy ( 1999 values ) . Therapy with enoxaparin was , therefore , considered to be the dominant strategy . Univariate sensitivity analysis indicated that the decision model was not robust to changes in the 30-day composite end-point , probability of recurrent angina , or base costs for treatment of recurrent angina or enoxaparin therapy . CONCLUSION Enoxaparin is the dominant antithrombotic pharmacotherapeutic strategy for patients with unstable coronary artery disease Context In patients with unstable angina , combination therapy with clopidogrel plus aspirin has been shown to be more effective than aspirin alone in preventing myocardial infa rct ion , stroke , or cardiovascular death , but the cost-effectiveness of such therapy has yet to be determined . Contribution When the authors used a societal perspective and lifetime time horizon , combination therapy increased quality -adjusted life span at a cost that was within the traditionally accepted limits of cost-effectiveness . Caution s Data are not yet available to determine whether combination therapy for longer than 1 year remains cost-effective , due to the uncertainty of the relationship between long-term efficacy and risk for hemorrhage . The Editors The Clopidogrel in Unstable Angina to Prevent Recurrent Events ( CURE ) trial demonstrated that clopidogrel plus aspirin was superior to aspirin alone in preventing the composite outcome of myocardial infa rct ion , stroke , or cardiovascular death in the year following an acute coronary syndrome or nonQ-wave myocardial infa rct ion ( 1 ) . Although combination therapy is recommended for such patients for at least 1 month , the optimal duration is less clear ( 2 ) . In addition , the cost of clopidogrel complicates the decision to combine it with aspirin . Adding clopidogrel to aspirin is financially unattractive if done in all patients with coronary disease ( 3 ) but may be cost-effective in high-risk patients , for whom clopidogrel offers more substantial absolute risk reduction . To assess the cost-effectiveness of clopidogrel plus aspirin relative to aspirin alone in high-risk patients with coronary artery disease and to explore the optimal duration of therapy , we constructed a decision analytic Markov model comparing these treatment strategies after an acute coronary syndrome as defined in CURE . Methods We performed a cost-effectiveness analysis using a Markov model ( 4 ) ( DATA 4.0 , TreeAge Software , Inc. , Williamstown , Massachusetts ) . We analyzed a reference case assuming a societal perspective ( 5 ) and a lifetime time horizon ( 6 ) . Our analysis was based on the CURE trial , a r and omized comparison of 3 to 12 months of therapy with clopidogrel plus aspirin or aspirin alone to prevent cardiovascular death , myocardial infa rct ion , or stroke in 12562 patients with an acute coronary syndrome ( 1 ) . We discounted costs and utilities at 3 % annually and determined lifetime costs , quality -adjusted life expectancy , and the incremental cost-effectiveness ratio . Sensitivity analyses included 1-way analyses on all data inputs ; probabilistic sensitivity analysis ; evaluation of varying duration of combination therapy , including potential loss of efficacy over time ; and consideration of population s with varying risk . Target Population The target population was analogous to that of the CURE trial ( 1 ) : patients with an acute coronary syndrome characterized by electrocardiographic changes or elevated serum cardiac markers in association with chest pain . Patients who had prolonged ST-segment elevation , who had undergone revascularization in the previous 3 months , who were at risk for severe bleeding or heart failure , or who had been treated with oral anticoagulants or glycoprotein IIb/IIIa inhibitors in the preceding 3 days were excluded . On the basis of the average age of CURE patients , we considered a 64-year-old as our base case and explored other ages in sensitivity analysis . We compared treatment costs and clinical outcomes for 2 types of antiplatelet therapy : 1 ) aspirin alone , 325 mg/d , and 2 ) clopidogrel , 75 mg/d , plus aspirin , 325 mg/d , for 1 year , followed by aspirin monotherapy . Model Structure In our model , we included vascular events : myocardial infa rct ion , stroke , vascular death and revascularization , intracerebral and gastrointestinal hemorrhagic events , and clopidogrel-associated thrombotic thrombocytopenic purpura . We included age-related mortality , correcting for events explicitly included in the model . We did not directly include procedures or outcomes , such as congestive heart failure , that CURE did not specifically address ( 1 ) . We indirectly accounted for the cost of such events by using age-adjusted annual health care costs ( 7 ) . This assumes equal probability of such events in each arm of the analysis . We allowed for multiple events , including multiple events of a particular type , within a given monthly cycle . We created Markov states for conditions that changed quality of life , annual cost , or probability of future events . For events with temporary decrements in quality of life , we assessed a utility toll proportional to the duration of hospitalization required ( 8) . We also modeled each combination of 2 events . When more than 2 events occurred , we used the Markov state that combined the 2 events with the lowest utility ( Figure 1 ) . Figure 1 . Schematic representation of the decision model . Model Inputs Probabilities We derived probabilities for vascular and hemorrhagic events over the first year of our analysis from the CURE trial ( 1 ) . Rates of cardiovascular outcomes were highest in the month immediately following the acute coronary syndrome ( 1 ) . To account for temporal variation in risk , we calculated probabilities for the first month separately from those for subsequent months . Beyond the time frame of the CURE trial , we empirically calculated declining probability functions for myocardial infa rct ion , cardiovascular death , and revascularization on the basis of proportional decline in risk over time in survivors of nonQ-wave myocardial infa rct ion ( 9 ) . We assumed that all bleeding events , other than intracerebral hemorrhage , were gastrointestinal . Because intracerebral hemorrhage was equally likely for the 2 treatment strategies ( 1 ) , all of the excess bleeding in the clopidogrel plus aspirin arm was attributed to gastrointestinal causes . The rate of thrombotic thrombocytopenic purpura associated with clopidogrel was derived from an observational study ( 10 , 11 ) . We represented uncertainty in event rates through distributions based on the number of events that occurred and the number of patient-years at risk . We obtained age-specific mortality from life tables ( 12 ) and corrected for death rates of events explicitly included in our model ( Table ) . Table . Model Inputs Efficacy of Combination Therapy Despite the variation in risk , the relative efficacy of clopidogrel plus aspirin did not vary between the first and subsequent months ( 1 ) . In modeling beyond the time frame of the CURE trial , we assumed in our base case that efficacy remained constant , on the basis of data for clopidogrel monotherapy ( 13 ) . We explored waning efficacy over time in sensitivity analysis . We used 3 variables to describe loss of efficacy , duration of constant efficacy ( 1 year to lifetime ) , duration of efficacy deterioration ( 1 to 10 years ) , and the extent of efficacy decline relative to aspirin monotherapy ( none to complete loss ) . Costs We derived costs for each event and for chronic care of disabled patients from the literature . For medications , we used the average wholesale price in the United States as our base value ( 35 ) and considered prices negotiated by a large-volume purchaser in constructing the price range . Acute care costs for clinical events represent the direct costs of all medical care incurred during hospitalization . Chronic care costs represent direct expenditures for medications , procedures , and nursing care specific to the condition in question and were assessed for each month in the Markov state . For Markov states representing survival after either severe stroke or intracerebral hemorrhage and another event , we assumed 20 % of the long-term cost of the additional condition to account for overlapping therapy . We accounted for other health care costs by using age-adjusted annual health expenditures ( 7 ) . We up date d costs to 2002 U.S. dollars with a gross domestic product deflator ( 44 ) and generated log-normal distributions for each estimate for use in sensitivity analyses ( Table ) . Utilities We used published population -based utilities , representing either time-tradeoff or st and ard-gamble techniques . For Markov states representing 2 events , we combined utilities with multiplication ( 8) . For events and procedures that did not result in durable changes in the health state of the individual , we used disutility tolls based on the average duration of hospitalization ( 8) . We modeled uncertainty in utility estimates by calculating distributions based on the range of utility estimates in the literature ( Table ) . Sensitivity Analyses To assess the degree to which variation in any variable altered our results , we performed 1-way sensitivity analyses for each model input by analyzing the results at both extremes of its 95 % CI . In evaluating patients of different ages , we adjusted both age-related mortality and estimates of annual health care cost accordingly . To better underst and the distribution of the cost-effectiveness ratio for clopidogrel plus aspirin and the potential value of further research , we performed probabilistic sensitivity analysis using Monte Carlo simulation ( 45 , 46 ) . In each of 1000 simulations , the value for each model input was r and omly selected from its distribution . We constructed a cost-effectiveness acceptability curve by calculating the average net monetary benefit for each strategy in each simulation over cost-effectiveness thresholds ranging from no additional expenditure for the least expensive therapy to $ 100000 for each quality -adjusted life-year ( QALY ) gained . We then determined the proportion of simulations for which clopidogrel plus aspirin result ed in the greater net monetary benefit at each cost-effectiveness threshold . We also assessed varying the duration of clopidogrel therapy from 1 month to 1 year in monthly increments . We considered prolonged therapy , up to patient lifetime , in yearly increments , simultaneously assessing potential decline in the efficacy of clopidogrel . To better BACKGROUND One-year follow-up data from the Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-Wave Coronary Events ( ESSENCE ) trial show that use of low-molecular-weight heparin ( enoxaparin ) compared with unfractionated heparin in patients hospitalized with unstable angina or non-Q-wave myocardial infa rct ion is associated with a 10 % reduction in the cumulative 1-year risk of death , myocardial infa rct ion , or recurrent angina . Given the higher acquisition cost of enoxaparin relative to unfractionated heparin , we assessed whether the reduced use of revascularization procedures and related care makes enoxaparin a cost-saving therapy in Canada . METHODS AND RESULTS We analyzed cumulative 1-year re source use data on the 1259 ESSENCE patients enrolled in Canadian centers ( 40 % of the total ESSENCE sample ) . Patient-specific data on use of drugs , diagnostic cardiac catheterization , percutaneous transluminal coronary angioplasty , coronary artery bypass grafting , and hospital days were available from the initial hospital stay and cumulative to 1 year . Hospital re sources were costed with the use of data from a teaching hospital in southern Ontario that is a participant in the Ontario Case Costing Project . During the initial hospital stay , use of enoxaparin was associated with reduced use of diagnostic catheterization and revascularization procedures , with the largest effect being reduced use of percutaneous transluminal coronary angioplasty ( 15.0 % vs 10.6 % ; P = .03 ) . At 1 year , the reduced risk and costs of revascularization more than offset increased drug costs for enoxaparin , producing a cost-saving per patient of $ 1485 ( 95 % confidence interval $ -93 to $ 3167 ; P = .06 ) . Sensitivity analysis with lower hospital per diem costs from a community hospital in Ontario still predicts cost savings of $ 1075 per patient over a period of 1 year . CONCLUSIONS The acquisition and administration cost of enoxaparin is higher than for unfractionated heparin ( $ 101 vs $ 39 ) , but in patients with acute coronary syndrome , the reduced need for hospitalization and revascularization over a period of 1 year more than offsets this initial difference in cost . Evidence from this Canadian sub study of ESSENCE supports the view that enoxaparin is less costly and more effective than unfractionated heparin in this indication OBJECTIVE To compare the efficacy , safety , cost and effects on platelet aggregation of unfractionated heparin and low-molecular weight heparin in unstable angina patients . PATIENTS AND METHODS Ninety-three patients with unstable angina were r and omized to receive either unfractionated heparin ( UFH ) or enoxaparin in an open design clinical trial with blinded end point evaluation . The effects of the heparins on platelet aggregation were also compared . RESULTS The composite end point of myocardial infa rct ion , cardiac death , recurrent angina and need for intervention was observed in 62 % of patients treated with UFH and in 37 % of patients treated with enoxaparin ( RR 1.7 , 95 % CI 0.75 to 3.71 , p = 0.04 ) . There was no difference in the frequency or severity of adverse events . A cost-effectiveness analysis showed both the heparins to be similar . Platelet aggregation was inhibited to a greater extent by UFH when compared to enoxaparin . CONCLUSIONS Enoxaparin appears to be superior in efficacy to UFH and similar to UFH in safety . No difference in costs was detected in this study . The greater inhibition of platelet aggregation observed in the case of UFH compared to enoxaparin indicates that there may be more bleeding complications with UFH BACKGROUND Comparative data for efficacy and safety between various low-molecular-weight heparins ( LMWHs ) in patients with unstable angina is not available . The present study was conducted to compare the efficacy , safety , cost-effectiveness and effects on plasminogen activator inhibitor-1 ( PAI-1 ) levels of three LMWHs -- enoxaparin , nadroparin and dalteparin . METHODS The study was a prospect i ve , r and omized , comparative , open with blinded endpoints ( PROBE design ) assessment with a 30-day follow-up . The primary endpoint of efficacy was a composite of cardiovascular death , myocardial infa rct ion , recurrent angina and need for intervention . Cost-effectiveness was calculated by calculating the incremental cost-effectiveness ratio . Plasma PAI-1 levels were estimated by ELISA . RESULTS A total of 150 patients were available for intention-to-treat analysis . There was no significant difference at 30 days in the primary endpoint or in any of the individual components in the three groups . The secondary endpoint of silent ischemia was also not significantly different . Adverse events were similar in the three groups . The PAI-1 levels were not significantly different in the three groups . The total cost of treatment in the three groups was similar . CONCLUSION Any of the three LMWHs evaluated in this study were similar with respect to efficacy , safety , PAI-1 levels and cost-effectiveness OBJECTIVE To evaluate the cost effectiveness of eptifibatide , a new glycoprotein IIb/IIIa receptor inhibitor , for the treatment of acute coronary syndromes ( ACS ) in Canada . DESIGN A model was created to analyze the cost effectiveness of eptifibatide using outcomes and re source utilization data from the Platelet Glycoprotein IIb/IIIa in Unstable Angina : Receptor Suppression Using Integrilin Therapy ( PURSUIT ) trial , an international , placebo controlled , r and omized clinical study evaluating the efficacy of eptifibatide in treating ACS . Cost data were derived from Canadian sources . Clinical outcomes were derived from published survival analyses based on North American PURSUIT data . SETTING The present analysis is representative of the Canadian health care setting . Data for re source use reflected actual re sources used by patients in the Canadian arm of the PURSUIT study . PATIENTS Patients included in the PURSUIT study were hospitalized for non-ST segment elevation ACS between November 1995 and January 1997 . INTERVENTIONS Eptifibatide or placebo treatment was r and omly assigned in addition to st and ard treatment with acetylsalicylic acid and heparin . MAIN RESULTS Per patient costs for hospitalization , medical procedures and medications associated with st and ard treatment plus placebo were 10,265 dollars compared with 10,691 dollars with eptifibatide , in 1995 Canadian dollars . Eptifibatide patients had lower rehospitalization rates in the six months following treatment . Discounting future health outcomes by 3 % , the cost effectiveness of treating ACS patients with eptifibatide in Canada was estimated as 5,165 dollars per year of life gained . CONCLUSIONS Considering both the cost of eptifibatide therapy over st and ard treatment and the health benefits associated with it , eptifibatide is a cost effective , economically attractive pharmacological option for the treatment of ACS patients in Canada BACKGROUND The combined use of antithrombotic agents , antiplatelet agents and invasive strategies in acute coronary syndrome without ST-segment elevation ( ACSWSTE ) reduces cardiovascular events . Fondaparinux has demonstrated equivalence to enoxaparin in reducing cardiovascular events , but with a lower rate of bleeding in patients using fondaparinux . OBJECTIVE Evaluate the cost-effectiveness of fondaparinux versus enoxaparin in patients with ACSWSTE in Brazil from the economic perspective of the Brazilian Unified Health System ( SUS ) . METHODS A decision analytic model was constructed to calculate the costs and consequences of the compared treatments . The model parameters were obtained from the OASIS-5 study ( N = 20,078 patients with ACSWSTE r and omized to fondaparinux or enoxaparin ) . The target outcome consisted of cardiovascular events ( i.e. , death , myocardial infa rct ion , refractory ischemia and major bleeding ) on days 9 , 30 and 180 after ACSWSTE . We evaluated all direct costs of treatment and ACSWSTE-related events . The year of the analysis was 2010 and the costs were described in reais ( R$ ) . RESULTS On day 9 , the cost of treatment per patient was R$ 2,768 for fondaparinux and R$ 2,852 for enoxaparin . Approximately 80 % of total costs were associated with invasive treatments . The drug costs accounted for 10 % of the total cost . The combined rates of cardiovascular events and major bleeding were 7.3 % and 9.0 % for fondaparinux and enoxaparin , respectively . Sensitivity analyses confirmed the initial results of the model . CONCLUSION The use of fondaparinux for the treatment of patients with ACSWSTE is superior to that of enoxaparin in terms of prevention of further cardiovascular events at lower cost PURPOSE The efficacy and safety of new antiplatelet therapies , as well as antiplatelet therapies in development , are review ed . SUMMARY Variability in the response to treatment with aspirin has been recognized for more than 40 years . Thienopyridine antiplatelet agents are now a st and ard pharmacologic component in the management of patients undergoing percutaneous coronary intervention ( PCI ) and stent placement . However , investigators have recently described wide inter-individual variability in the level of platelet inhibition following treatment with the thienopyridine clopidogrel , with a small number of patients classified as " non-responders " or " resistant . " Such variability in response is likely to have important clinical implication s , because antiplatelet therapy plays a key role in the prevention and treatment of cardiovascular disease , For example , recent studies have demonstrated that diminished response to clopidogrel may be associated with increased cardiac events after PCI . Even with larger-than-approved loading doses , clopidogrel requires several hours to reach a steady-state effect , and therapy must be discontinued for several days prior to surgery in order to avoid major bleeding events . Clinical trials of prasugrel , a new oral thienopyridine with a more rapid onset of platelet inhibition , have demonstrated significant reductions in adverse cardiovascular outcomes and stent thrombosis ; however , there is an increased risk for major bleeding events with prasugrel in some subgroups of the study population s. These limitations have led to development of agents that may potentially overcome such clinical challenges . AZD6140 , a novel , potent oral P2Y12 antagonist , demonstrated more effective platelet inhibition versus clopidogrel in a large r and omized trial of patients with acute coronary syndrome . However , patients taking AZD6140 reported dyspnea significantly more frequently than those taking clopidogrel . Cangrelor , a novel intravenous P2Y(12 ) receptor antagonist with a rapid onset of action and complete reversibility of platelet inhibition within 20 - 50 minutes of administration , may offer advantages over currently approved antiplatelet therapies . A new oral antiplatelet thrombin-receptor antagonist , TRA-SCH 530348 , is in early clinical trials . Unlike currently available drugs , TRA-SCH 530348 effectively prevents thrombin-induced activation of platelets . CONCLUSION Each new class of antiplatelet therapies has the potential for specific benefits and adverse effects in clinical use BACKGROUND The superiority of clopidogrel and aspirin versus aspirin alone for up to 1 year in patients who undergo percutaneous coronary intervention ( PCI ) after presenting with acute coronary syndromes without ST-segment elevation was demonstrated in the PCI-CURE study . We evaluated the long-term cost-effectiveness of clopidogrel use for up to 1 year using patient-level outcomes and re source use from PCI-CURE , and estimates of life expectancy gains based on external sources . METHODS PCI-CURE involved 2658 patients who underwent PCI between 1998 and 2000 after being r and omized in the CURE trial to clopidogrel ( n = 1313 ) or placebo ( n = 1345 ) . Roughly two thirds ( clopidogrel n = 821 , placebo n = 909 ) underwent PCI during the initial hospitalization ( early PCI ) . Costs were applied to hospitalizations according to diagnosis-related group . Clopidogrel was assigned the average wholesale price of 3.22 dollars per day . Life expectancy gains result ing from the prevention of major clinical events were estimated using external sources . RESULTS Average total costs were higher with clopidogrel ( difference [ based on costing method ] 253 dollars-423 dollars ) . For patients who underwent PCI during the initial hospitalization , the difference ranged from 155 dollars lower to 90 dollars higher with clopidogrel . The estimated life expectancy gain with clopidogrel was 0.0885 years , whereas it was 0.0962 years for the early PCI subgroup . Incremental cost per year of life gained with clopidogrel ranges from 2856 dollars to 4775 dollars overall and from dominant ( life expectancy benefit with cost savings ) to 935 dollars for the early PCI subgroup . CONCLUSIONS Clopidogrel given for up to 1 year in patients undergoing PCI after presentation with acute coronary syndromes is a highly cost-effective treatment strategy OBJECTIVES The purpose of this study was to evaluate the long-term cost-effectiveness of clopidogrel on top of st and ard therapy ( including ASA ) in patients with acute coronary syndromes without ST-segment elevation in Sweden . METHODS AND RESULTS Incremental cost-effectiveness ratios ( ICER ) were assessed using a Markov model with transition probabilities estimated from the Swedish hospital discharge and cause of death registers . Patients were assumed to be treated for 1 year , with treatment effects ( RR = 0.8 ) and costs taken from the Clopidogrel in Unstable Angina to prevent Recurrent ischaemic Events Trial . Two scenarios were analysed : with patients similar to those in the trial and with patients similar to those from the register . In the first scenario , the predicted net direct cost was 160 euro and the net total cost -54 euro , which with an incremental survival of 0.12 years give the ICER of 1365 euro per life-year gained from the health care payer perspective ( including direct costs ) and cost savings from the societal perspective ( also including indirect costs ) . The net costs in the second scenario were 149 euro , giving an ICER of 1009 euro for both perspectives . CONCLUSIONS Adding clopidogrel to st and ard therapy including ASA is cost-effective in the studied setting and compares favourably with other cardiovascular treatment and prevention strategies BACKGROUND Cardiovascular diseases account for nearly 20 % of all hospitalizations in Canada and consume 12 % of the total cost of all illnesses . With increasing trends of cardiovascular disease and increasing costs of care , development of cost-effective strategies is vital . The Clopidogrel in Unstable angina to prevent Recurrent Events ( CURE ) trial demonstrated the effectiveness of clopidogrel plus acetylsalicylic acid ( ASA ) compared with ASA alone in reducing cardiovascular events in patients with acute coronary syndromes and , in addition , patients undergoing percutaneous coronary intervention in the Percutaneous Coronary Intervention in CURE ( PCI-CURE ) trial . OBJECTIVE To assess the cost-effectiveness of clopidogrel in the Canadian health care system . METHODS Estimates of hospitalization costs were based on the 2003 cost schedules released by the Health Funding and Costing Branch of the Alberta Health and Wellness , as well as on the Case Mix Group classification system . Life expectancy beyond the trial was estimated from the Saskatchewan Health Data base . Cost-effectiveness was expressed as the incremental cost-effectiveness ratio , and bootstrap methods were used to estimate the joint distribution of costs and effectiveness . RESULTS Clopidogrel was shown to be cost-effective , with incremental cost-effectiveness ratios less than $ 10,000 per event prevented and less than $ 4,000 per life-year gained . The probability of clopidogrel result ing in cost per life-year gained of less than $ 20,000 was 0.975 for CURE patients and 0.904 for PCI-CURE patients . CONCLUSIONS The economic analysis demonstrated that clopidogrel combination therapy is not only cost-effective as antiplatelet therapy compared with ASA alone , but it is also cost-effective compared with other commonly used and openly reimbursed cardiovascular therapies in the Canadian health care system Abstract Objectives : To perform an evaluation from the societal perspective of the cost of treatment with enoxaparin sodium versus unfractionated heparin ( UFH ) in patients with unstable angina and non-Q wave myocardial infa rct ion in France . Design : Four complementary cost-minimisation analyses based on the results of the Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q wave Coronary Events ( ESSENCE ) international trial were conducted . We assessed differences in medical re source consumption and in duration of hospital stay in the whole study population ( n = 3171 ) and for the French patients ( n = 133 ) . Results : Results were consistent for the study group as a whole and for the French subgroup . Among patients treated with enoxaparin sodium , there was a statistically significant reduction in the use of angiography and percutaneous transluminal coronary angioplasty ( whole group study : p = 0.024 and 0.006 , respectively ) and a trend towards shorter lengths of hospital stay . The differences in angiography and angioplasty rates led to estimated average net cost savings with enoxaparin sodium of French Francs (FF)1555 per treated patient ( whole study population ) and FF9993 ( French subgroup ) [ 1996 values ] . The analyses based on the duration of hospital stay result ed in estimated net cost savings with enoxaparin sodium of between FF1014 per treated patient ( whole study population ) and FF2804 ( French subgroup ) . Conclusion : Our study confirmed earlier results which show that enoxaparin sodium is cost saving in the treatment of unstable angina |
13,886 | 29,996,680 | Conclusions The current meta- analysis suggests that smoking is associated with an increased risk of atrial fibrillation in a dose-dependent matter , but the association is weaker among former smokers compared to current smokers | Background Epidemiological studies on smoking and atrial fibrillation have been inconsistent , with some studies showing a positive association while others have found no association .
It is also unclear whether there is a dose – response relationship between the number of cigarettes smoked or pack-years and the risk of atrial fibrillation .
We conducted a systematic review and meta- analysis to clarify the association . | Aims Atrial fibrillation ( AF ) is associated with adverse outcome . Whether recently discovered genetic risk markers improve AF risk prediction is unknown . Methods and results We derived and vali date d a novel AF risk prediction model from 32 possible predictors in the Women 's Health Study ( WHS ) , a cohort of 20 822 women without cardiovascular disease ( CVD ) at baseline followed prospect ively for incident AF ( median : 14.5 years ) . We then created a genetic risk score ( GRS ) comprised of 12 risk alleles in nine loci and assessed model performance in the validation cohort with and without the GRS . The newly derived WHS AF risk algorithm included terms for age , weight , height , systolic blood pressure , alcohol use , and smoking ( current and past ) . In the validation cohort , this model was well calibrated with good discrimination [ C-index ( 95 % CI ) = 0.718 ( 0.684–0.753 ) ] and improved all reclassification indices when compared with age alone . The addition of the genetic score to the WHS AF risk algorithm model improved the C-index [ 0.741 ( 0.709–0.774 ) ; P = 0.001 ] , the category-less net reclassification [ 0.490 ( 0.301–0.670 ) ; P < 0.0001 ] , and the integrated discrimination improvement [ 0.00526 ( 0.0033–0.0076 ) ; P < 0.0001 ] . However , there was no improvement in net reclassification into 10-year risk categories of < 1 , 1–5 , and 5+% [ 0.041 ( −0.044–0.12 ) ; P = 0.33 ] . Conclusion Among women without CVD , a simple risk prediction model utilizing readily available risk markers identified women at higher risk for AF . The addition of genetic information result ed in modest improvements in predictive accuracy that did not translate into improved reclassification into discrete AF risk categories BACKGROUND Cigarette smoking increases the risk of coronary heart disease , but whether smoking increases atrial fibrillation ( AF ) is uncertain . OBJECTIVE The purpose of this study was to determine the association of cigarette smoking with incident AF in a population -based cohort of blacks and whites . METHODS We determined the risk of incident AF through December 2002 in relation to baseline ( 1987 - 1989 ) smoking status and cigarette-years of smoking in over 15,000 participants of the prospect i ve Atherosclerosis Risk in Communities ( ARIC ) study . RESULTS Over a mean follow-up of 13.1 years , 876 incident AF events were identified . Compared to never smokers , the multivariable-adjusted hazard ratios ( HRs ) for AF were 1.32 ( 95 % confidence interval [ CI ] 1.10 - 1.57 ) in former smokers , 2.05 ( 95 % CI 1.71 - 2.47 ) in current smokers , and 1.58 ( 95 % CI 1.35 - 1.85 ) in ever smokers . In the highest tertile of accumulated smoking amount ( > 675 cigarette-years ) , the incidence of AF was 2.10 times greater ( 95 % CI 1.74 - 2.53 ) than in those who never smoked . Associations were similar by gender , race , type of event ( AF and atrial flutter ) , and when only AF events identified by study exam ECGs were included . Finally , individuals who quit smoking exhibited a trend indicating a slightly lower risk of developing AF ( HR 0.88 , 95 % CI 0.65 - 1.17 ) compared to those who continued to smoke . CONCLUSION Smoking was associated with the incidence of AF , with more than a two-fold increased risk of AF attributed to current smoking . In addition , a trend toward a lower incidence of AF appeared among smokers who quit compared to continued smokers BACKGROUND Cigarette smoking is a known risk factor for cardiovascular disease ( CVD ) , but its relationship to the development of hypertension is unclear . Previous epidemiological studies have shown inconsistent results , having demonstrated inverse and positive associations between cigarette smoking and the development of hypertension . METHODS We analyzed 13,529 male participants from the Physicians ' Health Study free of baseline hypertension and CVD who provided information about smoking status . Smoking status was categorized as never , past , or current < 20 cigarettes/day , or current > or = 20 cigarettes/day . Incident hypertension was defined as either the initiation of antihypertensive treatment , self-reported systolic blood pressure ( BP ) > or = 140 mm Hg , or diastolic BP > or = 90 mm Hg . RESULTS Over a median follow-up of 14.5 years , 4,904 men developed hypertension . We modeled the risk of developing hypertension by baseline smoking status adjusting for known risk factors for hypertension or CVD . In a fully adjusted Cox proportional hazards model , we found that compared with never smokers , past smokers and current smokers had corresponding relative risks ( RRs ) of 1.08 and 1.15 of developing hypertension . The risk for smokers did not appear to differ based on number of cigarettes smoked daily . Further , the RR of hypertension was higher for men with normal vs. prehypertensive levels of systolic ( SBP ) or diastolic BP ( DBP ) . CONCLUSIONS This prospect i ve cohort data suggests that cigarette smoking may be a modest but important risk factor for the development of hypertension The validity of atrial fibrillation ( AF ) diagnoses in national registers for use as endpoints in prospect i ve studies has not been evaluated . We studied the validity of AF diagnoses in Swedish national hospital discharge and cause of death registers and the occurrence of and risk factors for AF in a middle-aged Swedish population using these registers . Our study included the 30,447 individuals ( age 44–73 ) who attended baseline visits in 1991–1996 of the Malmö Diet and Cancer study . Individuals with a first AF diagnosis were identified by record linkage with national registers . A subset of cases was r and omly selected for validation by examination of electrocardiograms and patient records . Electrocardiograms were available in 98 % of the validation sample ( 95 % definitive AF , 3 % no AF ) . The 2 % with ECGs unavailable had probable AF . Baseline AF prevalence was 1.3 % , higher in men and increased with age . During 11.2 years of follow-up 1430 first AF diagnoses occurred . Risk factors were age , hypertension , BMI , diabetes , history of heart failure , history of myocardial infa rct ion and , in men but not women , current smoking . The strongest risk factors were history of heart failure ( hazard ratio men 4.5 , women 8.7 ) and myocardial infa rct ion ( hazard ratio men 2.0 , women 1.8 ) . The largest population attributable risks were observed for hypertension ( men 38 % , women 34 % ) and obesity ( men 11 % , women 10 % ) . In conclusion , case misclassification of AF in national registers is small , indicating feasibility of use in prospect i ve studies . Hypertension and obesity account for large portions of population risk in middle-aged individuals with low prevalence of manifest cardiac disease Atrial fibrillation ( AF ) is the most frequently encountered cardiac arrhythmia . It is a risk factor for stroke and premature death . We studied the temporal changes in the prevalence of AF from 1976 to 1994 in a r and om population aged 50 to 89 years . The prevalence of AF , diagnosed from electrocardiograms ( ECGs ) , was determined in 8,606 patients examined in 1976 to 1978 , in 8,943 patients examined in 1981 to 1983 , and in 6,733 subjects examined in 1991 to 1994 . Changes in prevalence of AF were estimated by logistic regression analysis . In men , the age-st and ardized prevalence of AF increased from 1.4 % in 1976 to 1978 ( odds ratio [ OR ] 1.0 , reference ) to 1.9 % in 1981 to 1983 ( OR 1.6 , 95 % confidence interval [ CI ] 1.1 to 2.1 ) , and to 3.3 % in 1991 to 1994 ( OR 2.3 , 95 % CI 1.6 to 3.4 , p<0.001 , adjusted for age ) . In women , the prevalence of AF decreased from 1.5 % in 1976 to 1978 ( OR 1.0 , reference ) to 1.0 % in 1981 to 1983 ( OR 0.7 , 95 % CI 0.5 to 1.0 ) , and to 1.1 % in 1991 to 1994 ( OR 0.7 , 95 % CI 0.5 to 1.0 ) , although the overall decrease was not significant ( p=0.11 , adjusted for age ) . After adjusting for changes in comorbidity , body weight , and height , the increase in the prevalence of AF in men from 1976 to 1978 and from 1991 to 1994 remained significant ( OR 1.9 , 95 % CI 1.3 to 2.8 , p=0.002 ) . Although unchanged in women , the prevalence of AF in men more than doubled from the 1970s to the 1990s . The factors responsible for this gender-specific increase in the prevalence of this common arrhythmia have yet to be identified BACKGROUND An atrial fibrillation ( AF ) risk score for a non-Western general population has not been established . Methods and Results : A total of 6,898 participants ( 30 - 79 years old ) initially free of AF have been prospect ively followed for incident AF since 1989 . AF was diagnosed when AF or atrial flutter was present on ECG at a biannual health examination ; was indicated as a current illness ; or was in the medical records during follow-up . Cox proportional hazard ratios were analyzed after adjusting for cardiovascular risk factors at baseline . During the 95,180 person-years of follow-up , 311 incident AF events occurred . We developed a scoring system for each risk factor as follows : 0/-5 , 3/0 , 7/5 , and 9/9 points for men/women in their 30 s-40 s , 50 s , 60 s , and 70 s , respectively ; 2 points for systolic hypertension , overweight , excessive drinking , or coronary artery disease ; 1 point for current smoking ; -1 point for moderate non-high-density lipoprotein-cholesterol ; 4 points for arrhythmia ; and 8 , 6 , and 2 points for subjects with cardiac murmur in their 30 s-40 s , 50 s , and 60 s , respectively ( C-statistic 0.749 ; 95 % confidence interval , 0.724 - 0.774 ) . Individuals with score ≤2 , 10 - 11 , or ≥16 points had , respectively , ≤1 % , 9 % , and 27 % observed probability of developing AF in 10 years . CONCLUSIONS We developed a 10-year risk score for incident AF using traditional risk factors that are easily obtained in routine outpatient clinics/health examinations without ECG Background Identification of individuals at risk for developing atrial fibrillation ( AF ) will help to target screening and preventive interventions . We aim ed to vali date the CHARGE-AF model ( including variables age , race , height , weight , blood pressure , smoking , antihypertensive medication , diabetes , myocardial infa rct ion and heart failure ) for prediction of five-year incident AF in a representative European population with a wide age range . Methods and results The CHARGE-AF model was calculated in 24,020 participants of the population -based EPIC Norfolk study with 236 cases of hospitalization with diagnosis of AF within five years . The model showed good discrimination ( c-statistic 0.81 , 95 % confidence interval ( CI ) 0.75–0.85 ) , but weak calibration ( Chi2-statistic 142 ) with an almost two-fold overestimation of AF incidence . A recalibration to characteristics of the European Prospect i ve Investigation into Cancer and Nutrition ( EPIC ) Norfolk cohort improved calibration considerably ( Chi2-statistic 13.3 ) , with acceptable discrimination in participants both > 65 and ≤65 years of age ( c-statistics 0.70 , 95 % CI 0.61–0.77 and 0.83 , 95 % CI 0.74–0.88 ) . The recalibrated model also showed good discrimination in participants free of cardiovascular disease ( c-statistics 0.80 , 95 % CI 0.75–0.84 ) . Categories of predicted risk ( < 2.5 % , 2.5–5 % or > 5 % ) showed good concordance with observed five-year AF incidence of 0.62 % , 3.49 % and 8.74 % ( log rank test p < 0.001 ) , respectively . Conclusion A recalibration of the CHARGE-AF model is necessary for accurate predictions of five-year risk of AF in the EPIC Norfolk population . The recalibrated model showed good discrimination across a wide age range and in individuals free of cardiovascular disease , and hence is broadly applicable in primary care to identify people at risk for development of AF BACKGROUND Cigarette smoking is an important risk factor for cardiovascular disease , but it is unknown whether it also contributes to the risk of atrial fibrillation . METHODS AND RESULTS The study is part of the Rotterdam Study , a population -based cohort study among subjects aged > or = 55 years . The association between cigarette smoking and the risk of atrial fibrillation was examined in 5,668 subjects without atrial fibrillation at baseline . During a median follow-up of 7.2 years , 371 cases of atrial fibrillation were identified . Relative risks ( RR ) were calculated with 95 % CIs using the Cox proportional hazards model , adjusted for age , gender , body mass index , hypertension , systolic blood pressure , serum cholesterol level , diabetes mellitus , left ventricular hypertrophy on the electrocardiogram , prevalent and incident myocardial infa rct ion , prevalent heart failure , and the use of pulmonary medication . After multivariate adjustment , current smokers and former smokers had increased risks of atrial fibrillation as compared to never smokers ( RR 1.51 , 95 % CI 1.07 - 2.12 ; and RR 1.49 , 95 % CI 1.14 - 1.97 , respectively ) . No differences were found between men and women . CONCLUSIONS The results of this prospect i ve , population -based study show that current and former smoking of cigarettes are associated with increased risk of atrial fibrillation AIMS Obesity is a recognized risk factor for atrial fibrillation ( AF ) , partly because of the association between body mass index ( BMI ) and atrial volume . We aim ed to determine whether other factors relating to body size were related to AF . METHODS AND RESULTS Data were derived from a r and om population sample of 6903 men ( mean age 51.5 years ) who underwent a single midlife evaluation as part of the multifactor Swedish Primary Prevention Study . A total of 1253 men ( 18.2 % ) had a subsequent hospital discharge diagnosis ( principal or secondary ) of AF during a maximum follow-up of 34.3 years . Body surface area ( BSA ) at age 20 ( calculated from recalled weight and measured height ) was strongly related to subsequent AF ( P < 0.0001 ) , as were midlife BMI and weight gain from age 20 to midlife ( P < 0.0001 ) . In a Cox regression model which adjusted for midlife BMI , weight gain and other risk factors , hazard ratios ( HR ) [ 95 % confidence intervals ( CI ) ] for AF for the second , third , and fourth quartile of BSA at age 20 , compared with the lowest quartile , were 1.47 ( 95 % CI , 1.22 - 1.76 ) , 1.66 ( 95 % CI , 1.38 - 2.00 ) , and 2.22 ( 95 % CI , 1.82 - 2.70 ) ( P for trend < 0.0001 ) . CONCLUSION Large body size in youth , in an era when obesity was rare , as well as weight gain from age 20 to midlife , were both independently related to the development of AF . Given the current trends not only for obesity but also for height , a substantial increase in the incidence of AF is likely Background : Snus is a smokeless tobacco product , widely used among Swedish men and increasingly so elsewhere . There is debate as to whether snus is an acceptable “ harm-reduction ” tobacco product . Since snus use delivers a dose of nicotine equivalent to cigarettes , and has been implicated in cardiac arrhythmia because of associations with sudden cardiovascular death , a relation with atrial fibrillation is plausible and important to investigate . Methods : To assess the relation between use of snus and risk of atrial fibrillation , we carried out a pooled analysis of 7 prospect i ve Swedish cohort studies . In total , 274,882 men , recruited between 1978 and 2004 , were followed via the National Patient Register for atrial fibrillation . Primary analyses were restricted to 127,907 never-smokers . Relative risks were estimated using Cox proportional hazard regression . Results : The prevalence of snus use was 25 % among never-smokers . During follow-up , 3,069 cases of atrial fibrillation were identified . The pooled relative risk of atrial fibrillation was 1.07 ( 95 % confidence interval = 0.97–1.19 ) in current snus users , compared with nonusers . Conclusion : Findings from this large national pooling project indicate that snus use is unlikely to confer any important increase in risk of atrial fibrillation Lung cancer remains a devastating disease associated with substantial morbidity and mortality . Recent research has suggested that lung cancer screening with spiral computed tomography scans might reduce lung cancer mortality . Studies of lung cancer screening have also suggested that significant numbers of participants quit smoking after screening . However , most have relied solely on self-reported smoking behavior , which may be less accurate among participants in lung cancer screening . To assess the validity of self-reported smoking status among participants in a lung cancer screening trial , this study compared self-reported smoking status against urinary cotinine levels . The sample included 55 consecutive participants enrolled in a r and omized clinical trial comparing annual spiral computed tomography and chest X-ray for lung cancer screening . Participants were a mean of 59 years of age and predominantly Caucasian ( 96 % ) and male ( 55 % ) . Self-reported smoking status was assessed before and after participants learned of the purpose of the biochemical verification study . Using urinary cotinine as the “ gold st and ard , ” the sensitivity and specificity of self-reported smoking status were 91 % and 95 % , respectively ( κ = 0.85 , P < 0.001 , 95 % confidence interval = 0.71 - 0.99 ) . Total misclassification rate was 7 % . However , three of the four misclassified participants reported concurrent use of nicotine replacement strategies . Eliminating these cases from the analysis revealed sensitivity of 100 % and specificity of 95 % ( κ = 0.96 , P < 0.001 , 95 % confidence interval = 0.88 - 1.00 ) . In conclusion , self-reported smoking status among participants in a lung cancer screening trial was highly consistent with urinary cotinine test results . ( Cancer Epidemiol Biomarkers Prev 2006;15(10):1825–8 PURPOSE We examined the association between the body mass index analyzed as a continuous variable and by categorization according to World Health Organization criteria ( normal weight , overweight and obesity ) and the risk of a hospital ( inpatient as well as outpatient ) diagnosis of atrial fibrillation or flutter . METHODS Population -based prospect i ve cohort study conducted from December 1993 to December 2001 among 47589 participants ( 22482 men and 25107 women ) without preexisting cardiovascular or endocrine disease and with a mean age at baseline of 56 years ( range 50 - 64 years ) in the Danish Diet , Cancer , and Health Study . Subjects were followed up in the Danish National Registry of Patients and in the Danish Civil Registration System . RESULTS During follow-up ( mean , 5.7 years ) atrial fibrillation or flutter developed in 553 subjects ( 372 men and 181 women ) . The adjusted hazard ratio for atrial fibrillation or flutter per unit of increase in the body mass index was 1.08 ( 95 % confidence interval [ CI ] : 1.05 to 1.11 ) in men and 1.06 ( 95 % CI : 1.03 to 1.09 ) in women . When using normal weight as a reference , the adjusted hazard ratio for atrial fibrillation or flutter by overweight was 1.75 ( 95 % CI : 1.35 to 2.27 ) in men and 1.39 ( 95 % CI : 0.99 to 1.94 ) in women . The adjusted hazard ratio by obesity was 2.35 ( 95 % CI : 1.70 to 3.25 ) in men and 1.99 ( 95 % CI : 1.31 to 3.02 ) in women . CONCLUSION Overweight and obesity are associated with an increased risk of a diagnosis of atrial fibrillation or flutter The object of this article was to estimate the incidence rate of chronic atrial fibrillation ( AF ) in a general practice setting , to identify factors predisposing to its occurrence , and to describe treatment patterns in the year following the diagnosis . The method used was a population -based cohort study using the General Practice Research Data base ( GPRD ) in the UK . We identified patients aged 40 - 89 years with a first ever recorded diagnosis of AF . The diagnosis was vali date d through a question naire sent to the general practitioners . A nested case-control analysis was performed to assess risk factors for AF using 1,035 confirmed incident cases of chronic AF and a r and om sample of 5,000 controls from the original source population . The incidence rate of chronic AF was 1.7 per 1,000 person-years , and increased markedly with age . The age adjusted rate ratio among males was 1.4 ( 95 % CI 1.2 - 1.6 ) . The major risk factors were age , high BMI , excessive alcohol consumption , and prior cardiovascular comorbidity , in particular , valvular heart disease and heart failure . Digoxin was used in close to 70 % of the patients , and close to 15 % did not receive any antiarrhythmic treatment . Close to 40 % did not receive either warfarin or aspirin in the 3 months period after the diagnosis . Among the potential c and i date s for anticoagulation only 22 % of those aged 70 years or older were prescribed warfarin in comparison to 49 % among patients aged 40 - 69 years . Chronic AF is a disease of the elderly , with women presenting a lower incidence rate than men specially in young age . Age , weight , excessive alcohol consumption , and cardiovascular morbidity were the main independent risk factors for AF . Less than half of patients with chronic AF and no contraindications for anticoagulation received warfarin within the first trimester after the diagnosis OBJECTIVES We undertook this study to prospect ively evaluate whether cigarette smoking was associated with an increased risk of developing hypertension . BACKGROUND Smoking is a well-recognized risk factor for cardiovascular disease . Few prospect i ve cohort studies have examined the relationship between smoking and hypertension . METHODS We conducted a prospect i ve cohort study among 28,236 women in the Women 's Health Study who were initially free of hypertension , cardiovascular disease , and cancer . Detailed risk factor information , including smoking status , was collected from self-reported question naires . We used Cox proportional hazards survival models to calculate hazard ratios ( HRs ) and 95 % confidence intervals ( CIs ) of incident hypertension ( defined as either new diagnosis , the initiation of antihypertensive medication , systolic blood pressure > or = 140 mm Hg or diastolic blood pressure > or = 90 mm Hg ) . RESULTS At baseline , 51 % of women were never smokers , 36 % were former smokers , 5 % smoked 1 to 14 cigarettes , and 8 % smoked > or = 15 cigarettes per day . During a median of 9.8 years , there were 8,571 ( 30.4 % ) cases of incident hypertension . The age-adjusted HRs of developing hypertension among never , former , and current smokers of 1 to 14 and > or = 15 cigarettes per day were 1.00 ( reference ) , 1.04 ( 95 % CI 0.99 to 1.09 ) , 1.00 ( 95 % CI 0.90 to 1.10 ) , and 1.10 ( 95 % CI 1.01 to 1.19 ) , respectively . In multivariable models further adjusting for lifestyle , clinical , and dietary variables , the corresponding HRs were 1.00 ( reference ) , 1.03 ( 95 % CI 0.98 to 1.08 ) , 1.02 ( 95 % CI 0.92 to 1.13 ) , and 1.11 ( 95 % CI 1.03 to 1.21 ) , respectively . Among women who smoked > or = 25 cigarettes per day , the multivariable HR was 1.21 ( 95 % CI 1.06 to 1.39 ) . CONCLUSIONS In this large cohort of women , cigarette smoking was modestly associated with an increased risk of developing hypertension , with an effect that was strongest among women smoking at least 15 cigarettes per day BACKGROUND The combined impact of multiple lifestyle factors on risk of atrial fibrillation ( AF ) remains unclear . We investigated the joint association of four modifiable lifestyle factors on incidence of AF in a prospect i ve study of men and women . METHODS The study cohort comprised 39 300 men in the Cohort of Swedish Men and 33 090 women in the Swedish Mammography Cohort who were 45 - 83 years of age and free from atrial fibrillation at baseline . Healthy lifestyle was defined as body mass index < 25 kg/m(2 ) , regular exercise for ≥ 20 min/day , no or light-to-moderate alcohol consumption ( ≤ 2 drinks/day for men and ≤ 1 drink/day for women ) , and not smoking . Incident AF cases were identified through linkage with the Swedish National Inpatient Register . RESULTS During a mean follow-up of 10.9 years , AF occurred in 4028 men and 2539 women . Compared with men and women with no healthy lifestyle factors , the multivariable relative risks ( 95 % confidence interval ) of AF were 0.83 ( 0.65 - 1.07 ) for one , 0.74 ( 0.58 - 0.94 ) for two , 0.62 ( 0.49 - 0.79 ) for three , and 0.50 ( 0.39 - 0.64 ) for four healthy lifestyle factors ( P for trend < 0.0001 ) . The inverse association was similar in men and women . CONCLUSIONS Four healthy lifestyle factors combined were associated with a halving of the risk of AF |
13,887 | 31,304,323 | Users ’ preferences of social features were mixed : some felt more motivated by social support and competition , while others expressed concerns about comparison , indicating that a one-size-fits-all approach is insufficient .
In summary , this is an emerging area of research , with limited evidence suggesting that social features may increase user engagement . | Mobile health ( mHealth ) technologies have increasingly been used in interventions to promote physical activity ( PA ) , yet , they often have high attrition rates .
Integrating social features into mHealth has the potential to engage users ; however , little is known about the efficacy and user engagement of such interventions .
Thus , the aim of this systematic review was to characterize and evaluate the impact of interventions integrating social features in mHealth interventions to promote PA . | Background Web-based and mobile health interventions ( also called “ Internet interventions ” or " eHealth/mHealth interventions ") are tools or treatments , typically behaviorally based , that are operationalized and transformed for delivery via the Internet or mobile platforms . These include electronic tools for patients , informal caregivers , healthy consumers , and health care providers . The Consoli date d St and ards of Reporting Trials ( CONSORT ) statement was developed to improve the suboptimal reporting of r and omized controlled trials ( RCTs ) . While the CONSORT statement can be applied to provide broad guidance on how eHealth and mHealth trials should be reported , RCTs of web-based interventions pose very specific issues and challenges , in particular related to reporting sufficient details of the intervention to allow replication and theory-building . Objective To develop a checklist , dubbed CONSORT-EHEALTH ( Consoli date d St and ards of Reporting Trials of Electronic and Mobile HEalth Applications and onLine TeleHealth ) , as an extension of the CONSORT statement that provides guidance for authors of eHealth and mHealth interventions . Methods A literature review was conducted , followed by a survey among eHealth experts and a workshop . Results A checklist instrument was constructed as an extension of the CONSORT statement . The instrument has been adopted by the Journal of Medical Internet Research ( JMIR ) and authors of eHealth RCTs are required to su bmi t an electronic checklist explaining how they addressed each subitem . Conclusions CONSORT-EHEALTH has the potential to improve reporting and provides a basis for evaluating the validity and applicability of eHealth trials . Subitems describing how the intervention should be reported can also be used for non- RCT evaluation reports . As part of the development process , an evaluation component is essential ; therefore , feedback from authors will be solicited , and a before-after study will evaluate whether reporting has been improved Developing an evidence base for making public health decisions will require using data from evaluation studies with r and omized and nonr and omized design s. Assessing individual studies and using studies in quantitative research syntheses require transparent reporting of the study , with sufficient detail and clarity to readily see differences and similarities among studies in the same area . The Consoli date d St and ards of Reporting Trials ( CONSORT ) statement provides guidelines for transparent reporting of r and omized clinical trials . We present the initial version of the Transparent Reporting of Evaluations with Nonr and omized Design s ( TREND ) statement . These guidelines emphasize the reporting of theories used and descriptions of intervention and comparison conditions , research design , and methods of adjusting for possible biases in evaluation studies that use nonr and omized design Background Women ’s physical activity levels decline during their transition to parenthood . Facebook is widely used by Australian mothers and provides the opportunity to target social networks in order to maintain and increase physical activity . Method This mixed method study aim ed to pilot and assess the usability of the Mums Step It Up Facebook app , a new team-based physical activity intervention for mothers with young children . A purposive sample of five “ Captain ” women with young children , were recruited through personal contacts . These women used the app to recruit 3–7 Facebook friends ( with children under 5 ) to join their respective teams ( total n = 25 ) . The app encourages women to take 10,000 steps a day measured by a pedometer . Women used the app for 28 days to log steps , interact with team mates and monitor progress . Physical activity was assessed at two time points ( baseline and final week ) using the Active Australia Survey . Usability testing with the five “ Captain ” women took place over two one hour face-to-face sessions . A question naire seeking feedback on the app was completed at time point two . Results Participants ’ total physical activity increased by an average of 177 minutes per week ( p = 0.01 ) . The complexity of the team forming process and issues using the Facebook environment , where a variety of devices and software platforms are used , was highlighted . Discussion A team-based Facebook app shows considerable promise for the recruitment and retention of participants to a social network-based physical activity intervention . A r and omised controlled trial to further evaluate the effectiveness of the intervention is warranted BACKGROUND Despite the increasing popularity of activity trackers , little evidence exists that they can improve health outcomes . We aim ed to investigate whether use of activity trackers , alone or in combination with cash incentives or charitable donations , lead to increases in physical activity and improvements in health outcomes . METHODS In this r and omised controlled trial , employees from 13 organisations in Singapore were r and omly assigned ( 1:1:1:1 ) with a computer generated assignment schedule to control ( no tracker or incentives ) , Fitbit Zip activity tracker , tracker plus charity incentives , or tracker plus cash incentives . Participants had to be English speaking , full-time employees , aged 21 - 65 years , able to walk at least ten steps continuously , and non-pregnant . Incentives were tied to weekly steps , and the primary outcome , moderate-to-vigorous physical activity ( MVPA ) bout min per week , was measured via a sealed accelerometer and assessed on an intention-to-treat basis at 6 months ( end of intervention ) and 12 months ( after a 6 month post-intervention follow-up period ) . Other outcome measures included steps , participants meeting 70 000 steps per week target , and health-related outcomes including weight , blood pressure , and quality -of-life measures . This trial is registered at Clinical Trials.gov , number NCT01855776 . FINDINGS Between June 13 , 2013 , and Aug 15 , 2014 , 800 participants were recruited and r and omly assigned to the control ( n=201 ) , Fitbit ( n=203 ) , charity ( n=199 ) , and cash ( n=197 ) groups . At 6 months , compared with control , the cash group logged an additional 29 MVPA bout min per week ( 95 % CI 10 - 47 ; p=0·0024 ) and the charity group an additional 21 MVPA bout min per week ( 2 - 39 ; p=0·0310 ) ; the difference between Fitbit only and control was not significant ( 16 MVPA bout min per week [ -2 to 35 ; p=0·0854 ] ) . Increases in MVPA bout min per week in the cash and charity groups were not significantly greater than that of the Fitbit group . At 12 months , the Fitbit group logged an additional 37 MVPA bout min per week ( 19 - 56 ; p=0·0001 ) and the charity group an additional 32 MVPA bout min per week ( 12 - 51 ; p=0·0013 ) compared with control ; the difference between cash and control was not significant ( 15 MVPA bout min per week [ -5 to 34 ; p=0·1363 ] ) . A decrease in physical activity of -23 MVPA bout min per week ( 95 % CI -42 to -4 ; p=0·0184 ) was seen when comparing the cash group with the Fitbit group . There were no improvements in any health outcomes ( weight , blood pressure , etc ) at either assessment . INTERPRETATION The cash incentive was most effective at increasing MVPA bout min per week at 6 months , but this effect was not sustained 6 months after the incentives were discontinued . At 12 months , the activity tracker with or without charity incentives were effective at stemming the reduction in MVPA bout min per week seen in the control group , but we identified no evidence of improvements in health outcomes , either with or without incentives , calling into question the value of these devices for health promotion . Although other incentive strategies might generate greater increases in step activity and improvements in health outcomes , incentives would probably need to be in place long term to avoid any potential decrease in physical activity result ing from discontinuation . FUNDING Ministry of Health , Singapore Background While there has been an explosion of mobile device applications ( apps ) promoting healthful behaviors , including physical activity and sedentary patterns , surprisingly few have been based explicitly on strategies drawn from behavioral theory and evidence . Objective This study provided an initial 8-week evaluation of three different customized physical activity-sedentary behavior apps drawn from conceptually distinct motivational frames in comparison with a commercially available control app . Study Design and Methods Ninety-five underactive adults ages 45 years and older with no prior smartphone experience were r and omized to use an analytically framed app , a socially framed app , an affectively framed app , or a diet-tracker control app . Daily physical activity and sedentary behavior were measured using the smartphone ’s built-in accelerometer and daily self-report measures . Results Mixed-effects models indicated that , over the 8-week period , the social app users showed significantly greater overall increases in weekly accelerometry-derived moderate to vigorous physical activity relative to the other three arms ( P values for between-arm differences = .04-.005 ; Social vs. Control app : d = 1.05 , CI = 0.44,1.67 ; Social vs. Affect app : d = 0.89 , CI = 0.27,1.51 ; Social vs. Analytic app : d = 0.89 , CI = 0.27,1.51 ) , while more variable responses were observed among users of the other two motivationally framed apps . Social app users also had significantly lower overall amounts of accelerometry-derived sedentary behavior relative to the other three arms ( P values for between-arm differences = .02-.001 ; Social vs. Control app : d = 1.10,CI = 0.48,1.72 ; Social vs. Affect app : d = 0.94 , CI = 0.32,1.56 ; Social vs. Analytic app : d = 1.24 , CI = 0.59,1.89 ) . Additionally , Social and Affect app users reported lower overall sitting time compared to the other two arms ( P values for between-arm differences < .001 ; Social vs. Control app : d = 1.59,CI = 0.92 , 2.25 ; Social vs. Analytic app : d = 1.89,CI = 1.17 , 2.61 ; Affect vs. Control app : d = 1.19,CI = 0.56 , 1.81 ; Affect vs. Analytic app : d = 1.41,CI = 0.74 , 2.07 ) . Conclusion The results provide initial support for the use of a smartphone-delivered social frame in the early induction of both physical activity and sedentary behavior changes . The information obtained also sets the stage for further investigation of subgroups that might particularly benefit from different motivationally framed apps in these two key health promotion areas . Trial Registration Clinical Trials.gov Background In young men , unhealthy lifestyle behaviours can be detrimental to their physical and /or mental health and set them on a negative health trajectory into adulthood . Despite this , there is a lack of evidence to guide development of effective health behaviour change interventions for young men . This study assessed the feasibility and preliminary efficacy of the ‘ HEYMAN ’ ( Harnessing Ehealth to enhance Young men ’s Mental health , Activity and Nutrition ) healthy lifestyle program for young men . Methods A pilot RCT with 50 young men aged 18–25 years r and omised to the HEYMAN intervention ( n = 26 ) or waitlist control ( n = 24 ) . HEYMAN was a 3-month intervention , targeted for young men to improve eating habits , activity levels and well-being . Intervention development was informed by a participatory research model ( PRECEDE-PROCEED ) . Intervention components included eHealth support ( website , wearable device , Facebook support group ) , face-to-face sessions ( group and individual ) , a personalised food and nutrient report , home-based resistance training equipment and a portion control tool . Outcomes included : feasibility of research procedures ( recruitment , r and omisation , data collection and retention ) and of intervention components . Generalized linear mixed models estimated the treatment effect at 3-months for the primary outcomes : pedometer steps/day , diet quality , well-being and several secondary outcomes . Results A 7-week recruitment period was required to enrol 50 young men . A retention rate of 94 % was achieved at 3-months post-intervention . Retained intervention participants ( n = 24 ) demonstrated reasonable usage levels for most program components and also reported reasonable levels of program component acceptability for attractiveness , comprehension , usability , support , satisfaction and ability to persuade , with scores ranging from 3.0 to 4.6 ( maximum 5 ) . No significant intervention effects were observed for the primary outcomes of steps/day ( 1012.7 , 95 % CI = −506.2 , 2531.6 , p = 0.191 , d = 0.36 ) , diet quality score ( 3.6 , 95 % CI = −0.4 , 7.6 , p = 0.081 , d = 0.48 ) or total well-being score ( 0.4 , 95 % CI = −1.6 , 2.5 , p = 0.683 , d = 0.11 ) . Significant intervention effects were found for daily vegetable servings , energy-dense , nutrient-poor foods , MVPA , weight , BMI , fat mass , waist circumference and cholesterol ( all p < 0.05 ) . Conclusions The HEYMAN program demonstrated feasibility in assisting young men to make some positive lifestyle changes . This provides support for the conduct of a larger , fully-powered RCT , but with minor amendments to research procedures and intervention components required . Trial registration Australian New Zeal and Clinical Trials Registry ACTRN12616000350426 BACKGROUND This pilot study evaluated the feasibility and preliminary effectiveness of a 10-week WhatsApp-based intervention aim ed at enhancing health-related physical fitness components and cardiovascular disease ( CVD ) risk factors compared with a face-to-face condition . METHODS Participants ( N.=32 ) were assigned to one of three groups : training group ( N.=16 ) , mobile group ( N.=7 ) and control group ( N.=9 ) . Training group and mobile group performed the same training program , based on strength training with elastics b and s and aerobic exercise , during 10 weeks ; only the delivery mode differed . RESULTS The mobile group increased h and grip strength , aerobic capacity and decreased systolic blood pressure and heart rate after exercise though there were no significant differences respect to control group . The training group decreased significantly systolic blood pressure ( P=0.038 ) , diastolic blood pressure ( P=0.005 ) , mean arterial pressure ( P=0.006 ) and heart rate after exercise ( P=0.002 ) , respect to control group . CONCLUSIONS Comparison between training and mobile group showed that WhatsApp-based physical activity intervention was less effective than face-to-face condition . The results indicate that the use of an online social network produced slight changes in some health-related physical fitness components and CVD risk factors In this article two new methods for building and evaluating eHealth interventions are described . The first is the Multiphase Optimization Strategy ( MOST ) . It consists of a screening phase , in which intervention components are efficiently identified for inclusion in an intervention or for rejection , based on their performance ; a refining phase , in which the selected components are fine tuned and issues such as optimal levels of each component are investigated ; and a confirming phase , in which the optimized intervention , consisting of the selected components delivered at optimal levels , is evaluated in a st and ard r and omized controlled trial . The second is the Sequential Multiple Assignment R and omized Trial ( SMART ) , which is an innovative research design especially suited for building time-varying adaptive interventions . A SMART trial can be used to identify the best tailoring variables and decision rules for an adaptive intervention empirically . Both the MOST and SMART approaches use r and omized experimentation to enable valid inferences . When properly implemented , these approaches will lead to the development of more potent eHealth interventions BACKGROUND Women with breast cancer undergoing chemotherapy experience a variety of physical and psychosocial symptoms , which have negative effect on women 's quality of life and psychological well-being . Although M-health technologies provides innovative and easily accessible option to provide psychosocial support , mobile phone based interventions remain limited for these women in China . OBJECTIVE To develop a new mobile application to offer information as well as social and emotional support to women with breast cancer undergoing chemotherapy to promote their self-efficacy and social support , thus improving symptom management strategies . METHODS Basing on previous theoretical framework which incorporated B and ura 's self-efficacy theory and the social exchange theory , a new mobile application , called Breast Cancer e-Support Program ( BCS ) was design ed , with the content and functionality being vali date d by the expert panel and women with breast cancer . RESULTS BCS App program has four modules : 1 ) Learning forum ; 2 ) Discussion forum ; 3 ) Ask-the-Expert forum ; and 4 ) Personal Stories forum . BCS program can be applied on both and roid mobile phones and iPhones to reach more women . CONCLUSIONS This is the first of its kind developed in China for women with breast cancer undergoing chemotherapy . A r and omized controlled trial is undertaking to test the effectiveness of BCS program Purpose : To compare the effectiveness of different combinations of social comparison feedback and financial incentives to increase physical activity . Design : R and omized trial ( Clinical trials.gov number , NCT02030080 ) . Setting : Philadelphia , Pennsylvania . Participants : Two hundred eighty-six adults . Interventions : Twenty-six weeks of weekly feedback on team performance compared to the 50th percentile ( n = 100 ) or the 75th percentile ( n = 64 ) and 13 weeks of weekly lottery-based financial incentive plus feedback on team performance compared to the 50th percentile ( n = 80 ) or the 75th percentile ( n = 44 ) followed by 13 weeks of only performance feedback . Measures : Mean proportion of participant-days achieving the 7000-step goal during the 13-week intervention . Analysis : Generalized linear mixed models adjusting for repeated measures and clustering by team . Results : Compared to the 75th percentile without incentives during the intervention period , the mean proportion achieving the 7000-step goal was significantly greater for the 50th percentile with incentives group ( 0.45 vs 0.27 , difference : 0.18 , 95 % confidence interval [ CI ] : 0.04 to 0.32 ; P = .012 ) but not for the 75th percentile with incentives group ( 0.38 vs 0.27 , difference : 0.11 , 95 % CI : −0.05 to 0.27 ; P = .19 ) or the 50th percentile without incentives group ( 0.30 vs 0.27 , difference : 0.03 , 95 % CI : −0.10 to 0.16 ; P = .67 ) . Conclusion : Social comparison to the 50th percentile with financial incentives was most effective for increasing physical activity Background : Online social networks ( OSNs ) are a new , promising approach for catalyzing health-related behavior change . To date , the empirical evidence on their impact has been limited . Purpose : Using a r and omized trial , we assessed the impact of a health-oriented OSN with accelerometer and scales on participant ’s physical activity , weight , and clinical indicators . Methods : A sample of 349 PeaceHealth Oregon employees and family members were r and omized to the iWell OSN or a control group and followed for 6 months in 2010 - 2011 . The iWell OSN enabled participants to connect with “ friends , ” make public postings , view contacts ’ postings , set goals , download the number of their steps from an accelerometer and their weight from a scale , view trends in physical activity and weight , and compete against others in physical activity . Both control and intervention participants received traditional education material on diet and physical activity . Laboratory data on weight and clinical indicators ( triglycerides , high-density lipoprotein , or low-density lipoprotein ) , and self-reported data on physical activity , were collected at baseline , 3 months , and 6 months . Results : At 6 months , the intervention group increased leisure walking minutes by 164 % compared with 47 % in the control group . The intervention group also lost more weight than the controls ( 5.2 pounds compared with 1.5 pounds ) . There were no observed significant differences in vigorous exercise or clinical indicators between the 2 groups . Among intervention participants , greater OSN use , as measured by number of private messages sent , was associated with a greater increase in leisure walking and greater weight reduction over the study period . Conclusions : The study provides evidence that interventions using OSNs can successfully promote increases in physical activity and weight loss 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 Background Regular physical activity reduces the risk of cardiovascular events , but most ischemic heart disease ( IHD ) patients do not obtain enough . Methods and Results ACTIVE REWARD ( A Clinical Trial Investigating Effects of a R and omized Evaluation of Wearable Activity Trackers with Financial Rewards ) was a 24‐week home‐based , remotely monitored , r and omized trial with a 16‐week intervention ( 8‐week ramp‐up incentive phase and 8‐week maintenance incentive phase ) and an 8‐week follow‐up . Patients used wearable devices to track step counts and establish a baseline . Patients in control received no other interventions . Patients in the incentive arm received personalized step goals and daily feedback for all 24 weeks . In the ramp‐up incentive phase , daily step goals increased weekly by 15 % from baseline with a maximum of 10 000 steps and then remained fixed . Each week , $ 14 was allocated to a virtual account ; $ 2 could be lost per day for not achieving step goals . The primary outcome was change in mean daily steps from baseline to the maintenance incentive phase . Ischemic heart disease patients had a mean ( SD ) age of 60 ( 11 ) years and 70 % were male . Compared with control , patients in the incentive arm had a significantly greater increase in mean daily steps from baseline during ramp‐up ( 1388 versus 385 ; adjusted difference , 1061 [ 95 % confidence interval , 386–1736 ] ; P<0.01 ) , maintenance ( 1501 versus 264 ; adjusted difference , 1368 [ 95 % confidence interval , 571–2164 ] ; P<0.001 ) , and follow‐up ( 1066 versus 92 ; adjusted difference , 1154 [ 95 % confidence interval , 282–2027 ] ; P<0.01 ) . Conclusions Loss‐framed financial incentives with personalized goal setting significantly increased physical activity among ischemic heart disease patients using wearable devices during the 16‐week intervention , and effects were sustained during the 8‐week follow‐up . Clinical Trial Registration URL : https://www . clinical trials.gov . Unique identifier : NCT02531022 |
13,888 | 30,961,569 | Lifestyle modifications ( moderate exercise and weight loss ) , paracetamol , glucosamine , Intraarticular Hyaluronic Acid ( IAHA ) and platelet-rich-plasma ( PRP ) injections have a low risk of harm and beneficial ≥12 month outcomes .
Although Nonsteroidal Anti-inflammatory Drugs ( NSAIDs ) provide pain relief , they are associated with increased risk of medical complications .
Cortisone injections are associated with radiological cartilage degeneration at > 12 months .
Arthroscopy for degenerative meniscal tears in KOA leads to a 3-fold increase in total knee arthroplasty ( TKA ) .
TKA improves primary outcomes of KOA but has a low rate of significant medical complications .
Treatment with opioids has a lack of evidence for use and a high risk of long-term harm .
The use of IAHA and PRP may provide additional symptomatic benefit without the risk of harm .
TKA is associated with significant medical complications but is justified by the efficacy of joint replacement in late-stage disease . | Background There is no cure for knee osteoarthritis ( KOA ) and typically patients live approximately 30-years with the disease .
Most common medical treatments result in short-term palliation of symptoms with little consideration of long-term risk .
This systematic review aims to appraise the current evidence for the long-term ( ≥12 months ) safety of common treatments for knee osteoarthritis ( KOA ) . | The aim of the study was to evaluate the safety and efficacy of viscosupplementation with hylan G-F 20 in patients with mild to moderate osteoarthritis ( OA ) presenting with persistent knee pain 4–12 weeks after arthroscopic meniscectomy . A prospect i ve , multi-centre , open study was carried out in patients with pain due to OA of the knee , not resolved by simple analgesics , 4–12 weeks after undergoing arthroscopic meniscectomy . To be eligible , patients had to score ≥50 mm and ≤90 mm on both walking pain and patient global assessment visual analogue scales ( VAS ; 0–100 mm ) at baseline and be radiologically diagnosed pre-operatively with OA grade I or II on the Kellgren-Lawrence scale , with < 50 % joint space narrowing . Patients received three intra-articular , 2 ml injections of hylan G-F 20 in the target knee with an interval of 1 week between injections , and were followed for 52 weeks . The primary efficacy endpoint was the change from baseline in the walking pain VAS score at 26 weeks . Secondary outcome measures were the walking pain VAS scores at all other time points , the WOMAC Index at all time points , and patient and physician global assessment at all time points . The safety of the treatment was assessed using adverse event ( AE ) reports . A total of 62 patients ( mean age 55.4 years , 52 % male ) were enrolled . The mean walking pain VAS score decreased by 36.8 mm from baseline at 26 weeks ( P < 0.0001 ) , and also showed statistically significant decreases ( P < 0.0001 ) at all other time points . The change in WOMAC total and subscale scores from baseline were statistically significant ( P < 0.0001 ) at all time points , as were the decreases in the physician and patient global assessment VAS scores . There were 18 target knee AEs ( mostly pain and /or swelling and /or effusion ) in 12 patients ( 19 % ) considered to be at least possibly related to treatment . The majority of these ( 78 % ) were mild or moderate in intensity . One patient ( 1.6 % ) experienced a serious adverse event ( synovitis ) in the target knee that was considered possibly related to study treatment . Hylan G-F 20 provides effective pain relief and improves stiffness and physical function in patients with mild to moderate OA presenting with persistent osteoarthritic pain 4–12 weeks after arthroscopic meniscectomy . Symptomatic efficacy was maximised at 12 weeks and maintained at 26 and 52 weeks . The type ( pain and /or swelling and /or effusion ) and the intensity ( mostly mild/moderate ) of AEs reported in this study are similar to those reported in other trials in different patient population s , but the incidence was higher ( 19 % ) . The risk/benefit of hylan G-F 20 in this particular population of patients is favourable Background Osteoarthritis is the most prevalent joint disease and a frequent cause of joint pain , functional loss , and disability . Osteoarthritis often becomes chronic , and conventional treatments have demonstrated only modest clinical benefits without lesion reversal . Cell-based therapies have shown encouraging results in both animal studies and a few human case reports . We design ed a pilot study to assess the feasibility and safety of osteoarthritis treatment with mesenchymal stromal cells ( MSCs ) in humans and to obtain early efficacy information for this treatment . Methods Twelve patients with chronic knee pain unresponsive to conservative treatments and radiologic evidence of osteoarthritis were treated with autologous exp and ed bone marrow MSCs by intra-articular injection ( 40 × 106 cells ) . Clinical outcomes were followed for 1 year and included evaluations of pain , disability , and quality of life . Articular cartilage quality was assessed by quantitative magnetic resonance imaging T2 mapping . Results Feasibility and safety were confirmed , and strong indications of clinical efficacy were identified . Patients exhibited rapid and progressive improvement of algofunctional indices that approached 65 % to 78 % by 1 year . This outcome compares favorably with the results of conventional treatments . Additionally , quantification of cartilage quality by T2 relaxation measurements demonstrated a highly significant decrease of poor cartilage areas ( on average , 27 % ) , with improvement of cartilage quality in 11 of the 12 patients . Conclusions MSC therapy may be a valid alternative treatment for chronic knee osteoarthritis . The intervention is simple , does not require hospitalization or surgery , provides pain relief , and significantly improves cartilage quality Systematic review s ( SRs ) are an increasingly popular evidence -based tool and are often used to answer complex research questions across many different research domains . Early SR methodology was advanced by social scientists , and the term meta- analysis was coined by a social scientist who also conducted research in psychology . SRs have recently become popular in healthcare and are likely to be beneficial in any field . The aim of this report is to highlight issues in SR conduct with a focus on the field of nutrition and to make recommendations on improving SR conduct in this area . Development of the research question is probably the most important step in conducting an SR . The 4 main components of an answerable question are 1 ) the patient , population , or problem ; 2 ) the intervention , independent variable , or exposure ; 3 ) the comparators ; and 4 ) the dependent variables or outcomes of interest . The question will be used to determine the optimal methods for conducting the SR . SRs often include study design s beyond r and omized trials and do not always include a meta- analysis of the results . Other topics explored include underst and ing and interpreting discordant review s and the importance of reporting tools [ eg , QUality Of Reporting Of Meta-analyses ( QUOROM Statement ) or CONsoli date d St and ards Of Reporting of Trials ( CONSORT Statement ) ] . Recommendations are then provided , such as developing a capacity-building program , search ing the primary literature for research gaps , and extending reporting tools such as the QUOROM Statement to the field of nutrition Objective To examine the long-term efficacy and safety of five intra-articular injections with hyaluronan in knee osteoarthritis . Methods A multicentre , r and omised , placebo-controlled double-blind study of 337 patients fulfilling the American College of Rheumatology ( ACR ) criteria for knee osteoarthritis ( clinical and laboratory ) and with a Lequesne algofunctional index score ( LFI ) of 10 or greater . Patients received a hyaluronan product ( sodium hyaluronate ; Hyalgan ) ( n=167 ) or saline ( n=170 ) intra-articularly weekly for 5 weeks and were followed up to 1 year . Time to recurrence was the primary efficacy parameter . LFI , pain on walking 50 m based on visual analogue scale ( VAS pain 50 m ) , paracetamol consumption , patients ' global assessment , Nottingham health profile , joint effusion and number of responders were secondary efficacy parameters . The efficacy parameters were analysed by intention to treat ( ITT ) and per protocol ( PP ) . All adverse events ( AE ) were recorded as safety parameters . Results Time to recurrence showed no significant treatment effect ( ITT analysis , p=0.26 ) . Change from baseline in LFI and VAS pain 50 m for the ITT population showed no treatment effect . Paracetamol consumption , patients ' global assessment , responder rates and AE displayed no significant difference between treatment groups , analysed by both ITT and PP . Treatment compliance was 95 % in the hyaluronan group and 99 % in the placebo group . No safety problems were registered . Conclusion In patients fulfilling the ACR criteria for osteoarthritis of the knee with moderate to severe disease activity ( LFI ≥10 ) , five intra-articular injections of hyaluronan did not improve pain , function , paracetamol consumption or other efficacy parameters 3 , 6 , 9 and 12 months after the treatment OBJECTIVE The Arthritis , Diet , and Activity Promotion Trial ( ADAPT ) was a r and omized , single-blind clinical trial lasting 18 months that was design ed to determine whether long-term exercise and dietary weight loss are more effective , either separately or in combination , than usual care in improving physical function , pain , and mobility in older overweight and obese adults with knee osteoarthritis ( OA ) . METHODS Three hundred sixteen community-dwelling overweight and obese adults ages 60 years and older , with a body mass index of > or = 28 kg/m(2 ) , knee pain , radiographic evidence of knee OA , and self-reported physical disability , were r and omized into healthy lifestyle ( control ) , diet only , exercise only , and diet plus exercise groups . The primary outcome was self-reported physical function as measured with the Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) . Secondary outcomes included weight loss , 6-minute walk distance , stair-climb time , WOMAC pain and stiffness scores , and joint space width . RESULTS Of the 316 r and omized participants , 252 ( 80 % ) completed the study . Adherence was as follows : for healthy lifestyle , 73 % ; for diet only , 72 % ; for exercise only , 60 % ; and for diet plus exercise , 64 % . In the diet plus exercise group , significant improvements in self-reported physical function ( P < 0.05 ) , 6-minute walk distance ( P < 0.05 ) , stair-climb time ( P < 0.05 ) , and knee pain ( P < 0.05 ) relative to the healthy lifestyle group were observed . In the exercise group , a significant improvement in the 6-minute walk distance ( P < 0.05 ) was observed . The diet-only group was not significantly different from the healthy lifestyle group for any of the functional or mobility measures . The weight-loss groups lost significantly ( P < 0.05 ) more body weight ( for diet , 4.9 % ; for diet plus exercise , 5.7 % ) than did the healthy lifestyle group ( 1.2 % ) . Finally , changes in joint space width were not different between the groups . CONCLUSION The combination of modest weight loss plus moderate exercise provides better overall improvements in self-reported measures of function and pain and in performance measures of mobility in older overweight and obese adults with knee OA compared with either intervention alone Background Osteoarthritis is the most prevalent joint disease and a common cause of joint pain , functional loss , and disability . Conventional treatments demonstrate only modest clinical benefits without lesion reversal . Autologous mesenchymal stromal cell ( MSC ) treatments have shown feasibility , safety , and strong indications for clinical efficacy . We performed a r and omized , active control trial to assess the feasibility and safety of treating osteoarthritis with allogeneic MSCs , and we obtain information regarding the efficacy of this treatment . Methods We r and omized 30 patients with chronic knee pain unresponsive to conservative treatments and showing radiological evidence of osteoarthritis into 2 groups of 15 patients . The test group was treated with allogeneic bone marrow MSCs by intra-articular injection of 40 × 106 cells . The control group received intra-articular hyaluronic acid ( 60 mg , single dose ) . Clinical outcomes were followed for 1 year and included evaluations of pain , disability , and quality of life . Articular cartilage quality was assessed by quantitative magnetic resonance imaging T2 mapping . Results Feasibility and safety were confirmed and indications of clinical efficacy were identified . The MSC-treated patients displayed significant improvement in algofunctional indices versus the active controls treated with hyaluronic acid . Quantification of cartilage quality by T2 relaxation measurements showed a significant decrease in poor cartilage areas , with cartilage quality improvements in MSC-treated patients . Conclusions Allogeneic MSC therapy may be a valid alternative for the treatment of chronic knee osteoarthritis that is more logistically convenient than autologous MSC treatment . The intervention is simple , does not require surgery , provides pain relief , and significantly improves cartilage quality BACKGROUND Treatment of osteoarthritis is usually limited to short-term symptom control . We assessed the effects of the specific drug glucosamine sulphate on the long-term progression of osteoarthritis joint structure changes and symptoms . METHODS We did a r and omised , double-blind placebo controlled trial , in which 212 patients with knee osteoarthritis were r and omly assigned 1500 mg sulphate oral glucosamine or placebo once daily for 3 years . Weightbearing , anteroposterior radiographs of each knee in full extension were taken at enrolment and after 1 and 3 years . Mean joint-space width of the medial compartment of the tibiofemoral joint was assessed by digital image analysis , whereas minimum joint-space width -- ie , at the narrowest point -- was measured by visual inspection with a magnifying lens . Symptoms were scored by the Western Ontario and McMaster Universities ( WOMAC ) osteoarthritis index . FINDINGS The 106 patients on placebo had a progressive joint-space narrowing , with a mean joint-space loss after 3 years of -0.31 mm ( 95 % CI -0.48 to -0.13 ) . There was no significant joint-space loss in the 106 patients on glucosamine sulphate : -0.06 mm ( -0.22 to 0.09 ) . Similar results were reported with minimum joint-space narrowing . As assessed by WOMAC scores , symptoms worsened slightly in patients on placebo compared with the improvement observed after treatment with glucosamine sulphate . There were no differences in safety or reasons for early withdrawal between the treatment and placebo groups . INTERPRETATION The long-term combined structure-modifying and symptom-modifying effects of gluosamine sulphate suggest that it could be a disease modifying agent in osteoarthritis Background Knee osteoarthritis ( OA ) is a major cause of pain and functional limitation in older adults , yet longer-term studies of medical treatment of OA are limited . Objective To evaluate the efficacy and safety of glucosamine and chondroitin sulphate ( CS ) , alone or in combination , as well as celecoxib and placebo on painful knee OA over 2 years . Methods A 24-month , double-blind , placebo-controlled study , conducted at nine sites in the US ancillary to the Glucosamine/chondroitin Arthritis Intervention Trial , enrolled 662 patients with knee OA who satisfied radiographic criteria ( Kellgren/Lawrence grade 2 or 3 changes and baseline joint space width of at least 2 mm ) . This subset continued to receive their r and omised treatment : glucosamine 500 mg three times daily , CS 400 mg three times daily , the combination of glucosamine and CS , celecoxib 200 mg daily , or placebo over 24 months . The primary outcome was a 20 % reduction in Western Ontario and McMaster University Osteoarthritis Index ( WOMAC ) pain over 24 months . Secondary outcomes included an Outcome Measures in Rheumatology/Osteoarthritis Research Society International response and change from baseline in WOMAC pain and function . Results Compared with placebo , the odds of achieving a 20 % reduction in WOMAC pain were celecoxib : 1.21 , glucosamine : 1.16 , combination glucosamine/CS : 0.83 and CS alone : 0.69 , and were not statistically significant . Conclusions Over 2 years , no treatment achieved a clinical ly important difference in WOMAC pain or function as compared with placebo . However , glucosamine and celecoxib showed beneficial but not significant trends . Adverse reactions were similar among treatment groups and serious adverse events were rare for all treatments OBJECTIVE To compare the efficacy and safety of intraarticular hylan and 2 hyaluronic acids ( HAs ) in osteoarthritis ( OA ) of the knee . METHODS This was a multicenter , patient-blind , r and omized controlled trial in 660 patients with symptomatic knee OA . Patients were r and omly assigned to receive 1 cycle of 3 intraarticular injections per knee of 1 of 3 preparations : a high molecular weight cross-linked hylan , a non-cross-linked medium molecular weight HA of avian origin , or a non-cross-linked low molecular weight HA of bacterial origin . The primary outcome measure was the change in the Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) pain score at 6 months . Secondary outcome measures included local adverse events ( effusions or flares ) in injected knees . During months 7 - 12 , patients were offered a second cycle of viscosupplementation . RESULTS Pain relief was similar in all 3 groups . The difference in changes between baseline and 6 months between hylan and the combined HAs was 0.1 on the WOMAC pain score ( 95 % confidence interval [ 95 % CI ] -0.2 , 0.3 ) . No relevant differences were observed in any of the secondary efficacy outcomes , and stratified analyses provided no evidence for differences in effects across different patient groups . There was a trend toward more local adverse events in the hylan group than in the HA groups during the first cycle ( difference 2.2 % [ 95 % CI -2.4 , 6.7 ] ) , and this trend became more pronounced during the second cycle ( difference 6.4 % [ 95 % CI 0.6 , 12.2 ] ) . CONCLUSION We found no evidence for a difference in efficacy between hylan and HAs . In view of its higher costs and potential for more local adverse events , we see no rationale for the continued use of hylan in patients with knee OA Purpose To compare the safety and efficacy of two different approaches of platelet-rich plasma ( PRP ) production methods as intra-articular injection treatment for knee cartilage degenerative lesions and osteoarthritis ( OA ) . Methods The study involved 144 symptomatic patients affected by cartilage degenerative lesions and OA . Seventy-two patients were treated with 3 injections of platelet concentrate prepared with a single-spinning procedure ( PRGF ) , the other 72 with 3 injections of PRP obtained with a double-spinning approach . The patients were evaluated prospect ively at the enrollment and at 2 , 6 , and 12 months ’ follow-up with IKDC , EQ-VAS and Tegner scores ; adverse events and patient satisfaction were also recorded . Results Both treatment groups presented a statistically significant improvement in all the scores evaluated at all the follow-up times . Better results were achieved in both groups in younger patients with a lower degree of cartilage degeneration . The comparative analysis showed similar improvements with the two procedures : in particular , IKDC subjective evaluation increased from 45.0 ± 10.1 to 59.0 ± 16.2 , 61.3 ± 16.3 , and 61.6 ± 16.2 at 2 , 6 , and 12 months in the PRGF group , and from 42.1 ± 13.5 to 60.8 ± 16.6 , 62.5 ± 19.9 , and 59.9 ± 20.0 at 2 , 6 , and 12 months in the PRP group , respectively . Concerning adverse events , more swelling ( P = 0.03 ) and pain reaction ( P = 0.0005 ) , were found after PRP injections . Conclusions Although PRP injections produced more pain and swelling reaction with respect to that produced by PRGF , similar results were found at the follow-up times , with a significant clinical improvement with respect to the basal level . Better results were achieved in younger patients with a low degree of cartilage degeneration . Level of evidence II BACKGROUND This safety and feasibility study used autologous adipose-derived stromal vascular cells ( the stromal vascular fraction [ SVF ] of adipose tissue ) , to treat 8 osteoarthritic knees in 6 patients of grade I to III ( K-L scale ) with initial pain of 4 or greater on a 10-point Visual Analog Scale ( VAS ) . OBJECTIVES The primary objective of the study was evaluation of the safety of intra-articular injection of SVF . The secondary objective was to assess initial feasibility for reduction of pain in osteoarthritic knees . METHODS Adipose-derived SVF cells were obtained through enzymatic disaggregation of lipoaspirate , resuspension in 3 mL of Lactated Ringer 's Solution , and injection directly into the intra-articular space of the knee , with a mean of 14.1 million viable , nucleated SVF cells per knee . Metrics included monitoring of adverse events and preoperative to postoperative changes in the Western Ontario and McMaster Universities Arthritis Index ( WOMAC ) , the VAS pain scale , range of motion ( ROM ) , timed up- and -go ( TUG ) , and MRI . RESULTS No infections , acute pain flares , or other adverse events were reported . At 3-months postoperative , there was a statistically significant improvement in WOMAC and VAS scores ( P < .02 and P < .001 , respectively ) , which was maintained at 1 year . Physical therapy measurements for ROM and TUG both improved from preoperative to 3-months postoperative . St and ard MRI assessment from preoperative to 3-months postoperative showed no detectable structural differences . All patients attained full activity with decreased knee pain . CONCLUSIONS Autologous SVF was shown to be safe and to present a new potential therapy for reduction of pain for osteoarthritis of the knee . LEVEL OF EVIDENCE 4 : Therapeutic OBJECTIVES To describe the long-term effects of Hylan GF-20 viscosupplementation in patients with knee osteoarthritis and to identify factors predicting efficacy . METHODS One hundred and fifty-five patients ( 80 women and 75 men ; mean age , 69 years ) with symptomatic knee osteoarthritis each received three intraarticular Hylan GF-20 injections . Effectiveness , safety , and satisfaction were evaluated 7 - 14 months later based on a physician 's examination and a five-item question naire . Radiological data ( distribution and degree of joint space loss ) , size of the effusion ( none , moderate , large ) , injection route ( anterior , medial to the patella , or lateral to the patellar ) , and side effects were recorded . Factors predicting effectiveness were looked for by univariate analysis followed by multivariable analysis with adjustments on age , body mass index , gender , and time from treatment to question naire administration . RESULTS Satisfaction was good in 78 % and 58.9 % of the patients according to the physician examination and question naire , respectively . Safety was considered excellent or good in 96.2 % of the patients . Factors significantly ( P < 0.05 ) associated with a good outcome were a moderate effusion , injection lateral to the patella , joint space loss in a single compartment , and radiological meniscal calcinosis . CONCLUSION The factors predictive of a good response to Hylan GF-20 in this study need to be confirmed , and their impact quantitated , in prospect i ve studies OBJECTIVE : To test the feasibility of creating a valid and reliable checklist with the following features : appropriate for assessing both r and omised and non-r and omised studies ; provision of both an overall score for study quality and a profile of scores not only for the quality of reporting , internal validity ( bias and confounding ) and power , but also for external validity . DESIGN : A pilot version was first developed , based on epidemiological principles , review s , and existing checklists for r and omised studies . Face and content validity were assessed by three experienced review ers and reliability was determined using two raters assessing 10 r and omised and 10 non-r and omised studies . Using different raters , the checklist was revised and tested for internal consistency ( Kuder-Richardson 20 ) , test-retest and inter-rater reliability ( Spearman correlation coefficient and sign rank test ; kappa statistics ) , criterion validity , and respondent burden . MAIN RESULTS : The performance of the checklist improved considerably after revision of a pilot version . The Quality Index had high internal consistency ( KR-20 : 0.89 ) as did the subscales apart from external validity ( KR-20 : 0.54 ) . Test-retest ( r 0.88 ) and inter-rater ( r 0.75 ) reliability of the Quality Index were good . Reliability of the subscales varied from good ( bias ) to poor ( external validity ) . The Quality Index correlated highly with an existing , established instrument for assessing r and omised studies ( r 0.90 ) . There was little difference between its performance with non-r and omised and with r and omised studies . Raters took about 20 minutes to assess each paper ( range 10 to 45 minutes ) . CONCLUSIONS : This study has shown that it is feasible to develop a checklist that can be used to assess the method ological quality not only of r and omised controlled trials but also non-r and omised studies . It has also shown that it is possible to produce a checklist that provides a profile of the paper , alerting review ers to its particular method ological strengths and weaknesses . Further work is required to improve the checklist and the training of raters in the assessment of external validity The goal of this study was to assess the safety and efficacy of hyaluronan ( HA ) with/without corticosteroid in patients with knee osteoarthritis ( OA ) . In a 1-year , r and omized , single-blind trial , 24 patients were treated with HA weekly for 3 weeks , then three injections on the 6th month for a total of six injections . Sixteen patients were treated the same but with the addition of 1 ml triamcinolone acetonide prior to the first and fourth HA injection . The treatment was repeated at the sixth month . The patients were evaluated with the Western Ontario and McMaster University Osteoarthritis Index ( WOMAC ) and the visual analog pain scale ( VAS ) . After 1 year , progression of OA was evaluated with magnetic resonance imaging ( MRI ) . During the study , pain relief was marked in patients who received combined treatment with respect to WOMAC pain and VAS ( p<0.05 ) . At the first year , no progression was observed in either treatment group . Although all patients had improvement for both pain and function , HA together with corticosteroid was superior to HA alone for early pain relief . The MRI findings showed that neither treatment showed a progression on the damage of the cartilage BACKGROUND With more than 650,000 knee arthroscopies and 175,000 anterior cruciate ligament reconstructions performed annually in the United States , patients presenting for total knee arthroplasty are increasingly likely to have had previous knee surgery . The purpose of this study was to assess the prevalence of previous knee surgery in patients undergoing total knee arthroplasty and to test the hypothesis that patients with previous knee surgery undergo total knee arthroplasty at a younger age . METHODS All patients undergoing primary total knee arthroplasty over the study period who consented to enroll in a prospect i ve total joint registry were review ed . Inclusion criteria included a diagnosis of osteoarthritis or posttraumatic arthritis . RESULTS Of 1372 patients in the registry , 1286 met inclusion criteria . Twenty-nine percent had a history of knee surgery , and significantly more men ( 39 % ) than women ( 24 % ) had a history of knee surgery ( p < 0.0001 ) . Patients with previous knee surgery were significantly younger ( p < 0.0001 ) at total knee arthroplasty ; the mean age ( and st and ard deviation ) was 59 ± 10 years for patients with previous knee surgery compared with 66.6 ± 10.4 years for patients without previous knee surgery . Patients with a history of ligament reconstruction underwent total knee arthroplasty at a significantly younger age ( p < 0.0001 ) than patients with a history of other knee surgery ; the mean age ( and st and ard deviation ) was 50.2 ± 9.1 years for patients with a history of ligament reconstruction and 59.9 ± 9.6 years for patients with a history of other knee surgery . Among patients who had not undergone previous knee surgery , women underwent total knee arthroplasty at a significantly younger age ( p < 0.001 ) than men ; the mean age ( and st and ard deviation ) was 65.4 ± 10.3 years for women and 69.3 ± 10 years for men . However , there was no difference in age between the sexes in those with previous knee surgery ; the mean age ( and st and ard deviation ) was 58.6 ± 10.1 years for women and 59.6 ± 9.8 years for men . The average interval ( and st and ard deviation ) from previous knee surgery to total knee arthroplasty is 13.1 ± 12.6 years , longer in men ( 17.7 ± 13.8 years ) than in women ( 9.1 ± 9.8 years ) ( p < 0.0001 ) . CONCLUSIONS Patients with previous knee surgery undergo total knee arthroplasty at a significantly younger age than patients without previous knee surgery , especially men and patients with a history of ligament reconstruction . This may be a factor in the rising dem and for total knee arthroplasty . Future investigation to identify those at risk for early total knee arthroplasty after knee surgery and to develop methods to delay or to prevent the need for future total knee arthroplasty in these patients is warranted . LEVEL OF EVIDENCE Prognostic Level III . See Instructions for Authors for a complete description of levels of evidence We have previously demonstrated the efficacy of therapeutic exercise for osteoarthritis ( OA ) of the knee . This study was performed to examine the additive effects of glucosamine or risedronate on the exercise therapy . In this study , 142 female patients with moderate OA of the knee , who had been recommended to undergo home exercise at the first visit to the hospital , were r and omly given glucosamine hydrochloride , risedronate , or no additive . Although improvement after 18 months was observed in all groups using individual scales for evaluation of pain and function of the knee , no significant differences were observed between the groups regarding any of the scales , indicating no significant additive effect of glucosamine or risedronate . One reason for the lack of effect of glucosamine or risedronate on OA of the knee may be that the effect of these agents was occluded by the effect of therapeutic exercise to improve pain and function of the knee . This finding means that even if glucosamine and risedronate were to have an effect on OA of the knee , the effect would not be greater than the effect of knee exercise to improve the symptoms Objective To determine whether dietary intervention or knee strengthening exercise , or both , can reduce knee pain and improve knee function in overweight and obese adults in the community . Design Pragmatic factorial r and omised controlled trial . Setting Five general practice s in Nottingham . Participants 389 men and women aged 45 and over with a body mass index ( BMI ) of ≥28.0 and self reported knee pain . Interventions Participants were r and omised to dietary intervention plus quadriceps strengthening exercises ; dietary intervention alone ; quadriceps strengthening exercises alone ; advice leaflet only ( control group ) . Dietary intervention consisted of individualised healthy eating advice that would reduce normal intake by 2.5 MJ ( 600 kcal ) a day . Interventions were delivered at home visits over a two year period . Main outcome measures The primary outcome was severity of knee pain scored with the Western Ontario McMaster ( WOMAC ) osteoarthritis index at 6 , 12 , and 24 months . Secondary outcomes ( all at 24 months ) included WOMAC knee physical function and stiffness scores and selected domains on the SF-36 and the hospital anxiety and depression index . Results 289 ( 74 % ) participants completed the trial . There was a significant reduction in knee pain in the knee exercise groups compared with those in the non-exercise groups at 24 months ( percentage risk difference 11.61 , 95 % confidence interval 1.81 % to 21.41 % ) . The absolute effect size ( 0.25 ) was moderate . The number needed to treat to benefit from a ≥30 % improvement in knee pain at 24 months was 9 ( 5 to 55 ) . In those r and omised to knee exercise improvement in function was evident at 24 months ( mean difference −3.64 , −6.01 to −1.27 ) . The mean difference in weight loss at 24 months in the dietary intervention group compared with no dietary intervention was 2.95 kg ( 1.44 to 4.46 ) ; for exercise versus no exercise the difference was 0.43 kg ( −0.82 to 1.68 ) . This difference in weight loss was not associated with improvement in knee pain or function but was associated with a reduction in depression ( absolute effect size 0.19 ) . Conclusions A home based , self managed programme of simple knee strengthening exercises over a two year period can significantly reduce knee pain and improve knee function in overweight and obese people with knee pain . A moderate sustained weight loss is achievable with dietary intervention and is associated with reduced depression but is without apparent influence on pain or function . Trial registration Current Controlled Trials IS RCT N 93206785 OBJECTIVE To evaluate the safety and efficacy of long-term intraarticular ( IA ) steroid injections for knee pain related to osteoarthritis ( OA ) . METHODS In a r and omized , double-blind trial , 68 patients with OA of the knee received IA injections of triamcinolone acetonide 40 mg ( 34 patients ) or saline ( 34 patients ) into the study knee every 3 months for up to 2 years . The primary outcome variable was radiologic progression of joint space narrowing of the injected knee after 2 years . Measurements of minimum joint space width were performed by an automated computerized method on st and ardized fluoroscopically guided radiographs taken with the patient st and ing and with the knee in a semiflexed position . The clinical efficacy measure of primary interest was the pain subscale from the Western Ontario and McMaster Universities OA Index ( WOMAC ) . Efficacy measures of secondary interest were the total score on the WOMAC , physician 's global assessment , patient 's global assessment , patient 's assessment of pain , range of motion ( ROM ) of the affected knee , and 50-foot walking time . Clinical symptoms were assessed just before each injection . RESULTS At the 1-year and 2-year followup evaluations , no difference was noted between the two treatment groups with respect to loss of joint space over time . The steroid-injected knees showed a trend toward greater symptom improvement , especially at 1 year , for the WOMAC pain subscale , night pain , and ROM values ( P = 0.05 ) compared with the saline-injected knees . Using area under the curve analyses , knee pain and stiffness were significantly improved throughout the 2-year study by repeated injections of triamcinolone acetonide , but not saline ( P < 0.05 ) . CONCLUSION Our findings support the long-term safety of IA steroid injections for patients with symptomatic knee OA . No deleterious effects of the long-term administration of IA steroids on the anatomical structure of the knee were noted . Moreover , long-term treatment of knee OA with repeated steroid injections appears to be clinical ly effective for the relief of symptoms of the disease OBJECTIVE Osteoarthritis ( OA ) of the knee causes significant morbidity and current medical treatment is limited to symptom relief , while therapies able to slow structural damage remain elusive . This study was undertaken to evaluate the effect of glucosamine and chondroitin sulfate ( CS ) , alone or in combination , as well as celecoxib and placebo on progressive loss of joint space width ( JSW ) in patients with knee OA . METHODS A 24-month , double-blind , placebo-controlled study , conducted at 9 sites in the United States as part of the Glucosamine/Chondroitin Arthritis Intervention Trial ( GAIT ) , enrolled 572 patients with knee OA who satisfied radiographic criteria ( Kellgren/Lawrence [ K/L ] grade 2 or grade 3 changes and JSW of at least 2 mm at baseline ) . Patients with primarily lateral compartment narrowing at any time point were excluded . Patients who had been r and omized to 1 of the 5 groups in the GAIT continued to receive glucosamine 500 mg 3 times daily , CS 400 mg 3 times daily , the combination of glucosamine and CS , celecoxib 200 mg daily , or placebo over 24 months . The minimum medial tibiofemoral JSW was measured at baseline , 12 months , and 24 months . The primary outcome measure was the mean change in JSW from baseline . RESULTS The mean JSW loss at 2 years in knees with OA in the placebo group , adjusted for design and clinical factors , was 0.166 mm . No statistically significant difference in mean JSW loss was observed in any treatment group compared with the placebo group . Treatment effects on K/L grade 2 knees , but not on K/L grade 3 knees , showed a trend toward improvement relative to the placebo group . The power of the study was diminished by the limited sample size , variance of JSW measurement , and a smaller than expected loss in JSW . CONCLUSION At 2 years , no treatment achieved a predefined threshold of clinical ly important difference in JSW loss as compared with placebo . However , knees with K/L grade 2 radiographic OA appeared to have the greatest potential for modification by these treatments OBJECTIVE This study evaluated the safety of acetaminophen 4 g/d administered for up to 12 months to adult patients with osteoarthritis pain , using naproxen 750 mg/d as an active comparator . METHODS This multicenter , multidose , single-dummy , r and omized , double-blind , active-controlled , parallel-group study enrolled patients with mild to moderate osteoarthritis pain of the hip or knee . Patients received acetaminophen 4 g/d or naproxen 750 mg/d for 12 months ( group 1 ) or 6 months ( group 2 ) . Patients in both groups had follow-up visits at months 1 , 3 , and 6 of treatment ( or at the time of study withdrawal ) . Patients in group 1 also had follow-up visits at months 9 and 12 ( or at the time of study withdrawal ) . Tolerability evaluations consisted of determinations of hepatic ( aminotransferase activities ) and renal ( serum creatinine ) function , adverse events , and physical examinations . Adverse events reported by the patient or observed by the investigator during clinical evaluation were recorded . In addition , patients were question ed at each visit regarding the occurrence of adverse events using a nonspecific question . Investigators rated the intensity of adverse events and their subjective assessment of the relationship to study medication while blinded to the treatment group . At all visits , patients completed the Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) , in visual analog scale format , to assess pain , stiffness , and physical function over the previous 2 weeks . The primary efficacy end point was the mean change from baseline in the WOMAC pain subscale score at 6 months . Data from the 6- and 12-month groups were combined for analysis . RESULTS Of 581 r and omized patients , the safety population included 571 patients who received > or = 1 dose of study medication . The 571 patients had a mean ( SD ) age of 59.3 ( 8.6 ) years , 395 ( 69.2 % ) were female , and 480 ( 84.1 % ) were white . Of 290 patients r and omized to receive acetaminophen , 134 completed 3 months of treatment , 96 completed 6 months , 60 completed 9 months , and 55 completed a full 12 months . The median dose adherence ranged from 95.5 % to 98.6 % during the trial . The completion and adherence patterns were similar for patients receiving naproxen . Of 291 patients r and omized to receive naproxen , 151 completed 3 months , 124 completed 6 months , 85 completed 9 months , and 80 completed 12 months . The median dose adherence ranged from 96.4 % to 98.4 % during the trial . No patient in either treatment group experienced hepatic failure , hepatic dysfunction , aminotransferase levels > or = 2x the upper limit of the reference range , renal failure , or serum creatinine levels > or = 1.5x the upper limit of the reference range . No statistically significant differences were observed between the 2 treatment groups in the proportion of patients who reported > or = 1 adverse event ( 206 [ 71.8 % ] acetaminophen , 209 [ 73.6 % ] naproxen ) or in the proportion of patients who discontinued treatment because of adverse events ( 71 [ 24.7 % ] acetaminophen , 63 [ 22.2 % ] naproxen ) . Among adverse events considered to be drug related and reported by > or = 1 % of patients , constipation and peripheral edema were reported more frequently in the naproxen group than in the acetaminophen group ( 9.9 % vs 3.1 % [ P<0.002 ] and 3.9 % vs 1.0 % [ P<0.033 ] , respectively ) . No adverse event reported in the acetaminophen group was considered both serious and related to study medication . One subject in the naproxen group had an event that was considered serious and related to study drug : gastrointestinal bleeding . No statistically significant differences were observed between the 2 treatment groups for the primary efficacy end point . CONCLUSION With physician supervision , acetaminophen was found to be generally well tolerated in these patients for the treatment of osteoarthritis pain of the hip or knee for periods of up to 12 months OBJECTIVE To evaluate the long-term efficacy and safety of Hymovis ® in the symptomatic treatment of knee osteoarthritis ( OA ) . PATIENTS AND METHODS This is a prospect i ve , multi-center , open label , phase III clinical study . Two intra-articular injections ( 3 mL ) of Hymovis ® ( 8 mg/mL HYADD ® 4 ) were administered 1 week apart at the beginning of the study on day 0 and day 7 and after 6 months from baseline , on day 182 and 189 . Follow-up assessment were conducted for 52 weeks . 50 subjects , > 40 years old , with knee OA , with clinical and radiological confirm , complain pain in the target knee were enrolled . The variables considered were : WOMAC question naire , Joint Space Width ( JSW ) , OMERACT OARSI responder criteria , EQ-5D question naire , rescue medication consumption . RESULTS After the injections of Hymovis ® , pain perceived by the patient when walking on a flat surface ( WOMAC A1 score ) significantly improves at the end of the study respect to the baseline . WOMAC stiffness , physical function and total score significantly improve during the study since 3 months after treatment , and it is maintained up to the end of the study ( p < 0.001 ) . By the x-ray analysis of knee , a radiological progression of OA was observed in the 26 % of patients at the end of the study , while 88 % of patients result to be responder to the therapy classified as per OMERACT-OARSI criteria . The EQ-5D weighted index increased significantly , against baseline , at each study time point ( p < 0.001 ) . Investigator 's and patient 's global assessment of the disease measured by the VAS both show a marked improvement in patient 's health conditions . CONCLUSIONS Results from this study confirm that Hymovis ® alleviate the knee pain since the first treatment cycle . The patients treated with two cycles of intra-articular injections of Hymovis ® have a progressive pain reduction that is maintained up to one year after the treatment start with improve of all the scores considered in this study . Hymovis ® is effective and safe in symptomatic treatment of painful knee OA OBJECTIVE To study the efficacy and safety of single intra-articular injection of 6-mL hylan G-F 20 in Chinese patients with symptomatic knee osteoarthritis . DESIGN Prospect i ve case series . SETTING Six government hospitals in Hong Kong . PATIENTS Patients with primary knee osteoarthritis were recruited from six government hospitals from 1 October 2010 to 31 May 2012 . All patients received 6-mL intra-articular injection of hylan G-F 20 . MAIN OUTCOME MEASURES Pain visual analogue scale , functional visual analogue scale , and 5-point Likert scale on change of pain and function were assessed . Adverse events were checked . Radiographs were taken pre-injection and at 3 months and 1 year . RESULTS A total of 110 knees of 95 patients with primary knee osteoarthritis were treated . The mean age of the patients was 62 ( st and ard deviation , 9.8 ) years . All patients completed 1 year of follow-up . The mean pain visual analogue scale , functional visual analogue scale , and Likert value for pain and function showed statistically significant improvements at 6 weeks , 3 months , 6 months , and 1 year compared with the pre-injection values . No significant correlations were found between changes in visual analogue scale and age , body mass index , pre-injection radiological osteoarthritis severity , serum erythrocyte sedimentation rate , or C-reactive protein . Serial radiographs did not show any changes in the radiological severity of knee osteoarthritis . Overall , 16.4 % of the patients experienced mild and self-limiting adverse events . CONCLUSION Hylan G-F 20 is a safe and effective therapy to relieve pain and improve function for up to 1 year in Chinese patients with knee osteoarthritis PURPOSE The purpose of this study was to compare the efficacy and safety in a r and omized , clinical trial of 3 injections of PRGF-Endoret ( BTI Biotechnology Institute , Vitoria , Spain ) versus one single intra-articular injection of Durolane hyaluronic acid ( HA ) ( Q-MED AB , Uppsala , Sweden ) as a treatment for reducing symptoms in patients with knee osteoarthritis ( OA ) . METHODS Ninety-six patients with symptomatic knee OA were r and omly assigned to receive PRGF-Endoret ( 3 injections on a weekly basis ) or one infiltration with Durolane HA . The primary outcome measures were a 30 % decrease and a 50 % decrease in the summed score for the pain , physical function , and stiffness subscales of the Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) and Lequesne scores from baseline to weeks 24 and 48 . The percentage of OMERACT-OARSI ( Outcome Measures for Rheumatology Committee and Osteoarthritis Research Society International St and ing Committee for Clinical Trials Response Criteria Initiative ) responders was also documented . As secondary outcomes , pain , stiffness , and physical function by use of the WOMAC and the Lequesne score were considered and overall safety of the injection themselves . RESULTS The mean age of the patients was 63.6 years . Treatment with PRGF-Endoret was significantly more efficient than treatment with Durolane HA in reducing knee pain and stiffness and improving physical function in patients with knee OA . The rate of response to PRGF-Endoret was significantly higher than the rate of response to HA for all the scores including pain , stiffness , and physical function on the WOMAC , Lequesne index , and OMERACT-OARSI responders at 24 and 48 weeks . Adverse events were mild and evenly distributed between the groups . CONCLUSIONS Our findings show that PRGF-Endoret is safe and significantly superior to Durolane HA in primary and secondary efficacy analysis both at 24 and 48 weeks ; provides a significant clinical improvement , reducing patients ' pain and improving joint stiffness and physical function with respect to basal levels in patients with knee OA ; and should be considered in the treatment of patients with knee OA Background : Platelet-rich plasma ( PRP ) injections have become an intriguing treatment option for osteoarthritis ( OA ) , particularly OA of the knee . Despite the plethora of PRP-related citations , there is a paucity of high-level evidence that is comparable , cohort specific , dose controlled , injection protocol controlled , and double-blinded . Purpose : To determine the safety and efficacy of leukocyte-poor PRP autologous conditioned plasma ( ACP ) for knee OA treatment through a feasibility trial regulated by the US Food and Drug Administration ( FDA ) . Study Design : R and omized controlled trial ; Level of evidence , 1 . Methods : In accordance with FDA protocol , patient selection was based on strict inclusion /exclusion criteria ; 114 patients were screened , and 30 were ultimately included in the study . These patients were r and omized to receive either ACP ( n = 15 ) or saline placebo ( n = 15 ) for a series of 3 weekly injections . Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) scores served as the primary efficacy outcome measure . Patients were followed for 1 year . Results : No adverse events were reported for ACP administration . Furthermore , the results demonstrated no statistically significant difference in baseline WOMAC scores between the 2 groups . However , in the ACP group , WOMAC scores at 1 week were significantly decreased compared with baseline scores , and the scores for this group remained significantly lower throughout the study duration . At the study conclusion ( 12 months ) , subjects in the ACP group had improved their overall WOMAC scores by 78 % from their baseline score , compared with 7 % for the placebo group . Conclusion : ACP is safe and provides quantifiable benefits for pain relief and functional improvement with regard to knee OA . No adverse events were reported for ACP administration . After 1 year , WOMAC scores for the ACP subjects had improved by 78 % from their baseline score , whereas scores for the placebo control group had improved by only 7 % . Other joints affected with OA may also benefit from this treatment Importance Synovitis is common and is associated with progression of structural characteristics of knee osteoarthritis . Intra-articular corticosteroids could reduce cartilage damage associated with synovitis but might have adverse effects on cartilage and periarticular bone . Objective To determine the effects of intra-articular injection of 40 mg of triamcinolone acetonide every 3 months on progression of cartilage loss and knee pain . Design , Setting , and Participants Two-year , r and omized , placebo-controlled , double-blind trial of intra-articular triamcinolone vs saline for symptomatic knee osteoarthritis with ultrasonic features of synovitis in 140 patients . Mixed-effects regression models with a r and om intercept were used to analyze the longitudinal repeated outcome measures . Patients fulfilling the American College of Rheumatology criteria for symptomatic knee osteoarthritis , Kellgren-Lawrence grade s 2 or 3 , were enrolled at Tufts Medical Center beginning February 11 , 2013 ; all patients completed the study by January 1 , 2015 . Interventions Intra-articular triamcinolone ( n = 70 ) or saline ( n = 70 ) every 12 weeks for 2 years . Main Outcomes and Measures Annual knee magnetic resonance imaging for quantitative evaluation of cartilage volume ( minimal clinical ly important difference not yet defined ) , and Western Ontario and McMaster Universities Osteoarthritis index collected every 3 months ( Likert pain subscale range , 0 [ no pain ] to 20 [ extreme pain ] ; minimal clinical ly important improvement , 3.94 ) . Results Among 140 r and omized patients ( mean age , 58 [ SD , 8 ] years , 75 women [ 54 % ] ) , 119 ( 85 % ) completed the study . Intra-articular triamcinolone result ed in significantly greater cartilage volume loss than did saline for a mean change in index compartment cartilage thickness of −0.21 mm vs −0.10 mm ( between-group difference , −0.11 mm ; 95 % CI , −0.20 to −0.03 mm ) ; and no significant difference in pain ( −1.2 vs −1.9 ; between-group difference , −0.6 ; 95 % CI , −1.6 to 0.3 ) . The saline group had 3 treatment-related adverse events compared with 5 in the triamcinolone group and had a small increase in hemoglobin A1c levels ( between-group difference , −0.2 % ; 95 % CI , −0.5 % to −0.007 % ) . Conclusions and Relevance Among patients with symptomatic knee osteoarthritis , 2 years of intra-articular triamcinolone , compared with intra-articular saline , result ed in significantly greater cartilage volume loss and no significant difference in knee pain . These findings do not support this treatment for patients with symptomatic knee osteoarthritis . Trial Registration Clinical Trials.gov Identifier : Background : Knee osteoarthritis ( OA ) is the most common musculoskeletal disease among old individuals which affects ability for sitting on the chair , st and ing , walking and climbing stairs . Our objective was to investigate the short and long-term effects of the most simple and the least expensive exercise protocol s in combination to conventional conservative therapy for knee OA . Methods : It was a single blind RCT study with a 12-months follow-up . Totally , 56 patients with knee OA were assigned into 2 r and om groups . The patients in exercise group received exercise for knee muscles in combination with non-steroid anti-inflammatory drugs ( NSAIDs ) and 10 sessions acupuncture and physiotherapy modalities . Non-exercise group received similar treatments except exercise program . The changes in patients ’ pain and functional status were evaluated by visual analog scale ( VAS ) , knee and osteoarthritis outcome score ( KOOS ) question naire and functional tests ( 4 steps , 5 sit up , and 6 min walk test ) before and after treatment ( 1 and 3 months after intervention ) , and 1 year later at the follow-up . Results : The results showed that the patients with knee OA in exercise group had significant improvement in pain , disability , walking , stair climbing , and sit up speed after treatment at first and second follow-up when compared with their initial status and when compared with non-exercise group . At third follow up ( 1 year later ) there was significant difference between groups in VAS and in three items of KOOS question naire in functional status . Conclusion : Non aerobic exercises for muscles around knee can augment the effect of other therapeutic interventions like medical therapy , acupuncture , and modalities for knee OA |
13,889 | 26,599,471 | AUTHORS ' CONCLUSIONS A policy for planned early delivery versus expectant management for a suspected compromised fetus at term does not demonstrate any differences in major outcomes of perinatal mortality , significant neonatal or maternal morbidity or neurodevelopmental disability .
There was also a significant difference in the proportion of babies with a birthweight centile < 2.3rd , however this did not translate into a reduction in morbidity . | BACKGROUND Fetal compromise in the term pregnancy is suspected when the following clinical indicators are present : intrauterine growth restriction ( IUGR ) , decreased fetal movement ( DFM ) , or when investigations such as cardiotocography ( CTG ) and ultrasound reveal results inconsistent with st and ard measurements .
Pathological results would necessitate the need for immediate delivery , but the management for ' suspicious ' results remains unclear and varies widely across clinical centres .
There is clinical uncertainty as to how to best manage women presenting with a suspected term compromised baby in an otherwise healthy pregnancy .
OBJECTIVES To assess , using the best available evidence , the effects of immediate delivery versus expectant management of the term suspected compromised baby on neonatal , maternal and long-term outcomes . | Objective Pregnancies complicated by intrauterine growth retardation ( IUGR ) beyond 36 weeks of gestation are at increased risk of neonatal morbidity and mortality . Optimal treatment in IUGR at term is highly debated . Results from the multicenter DIGITAT ( Disproportionate Intrauterine Growth Intervention Trial At Term ) trial show that induction of labor and expectant monitoring result in equal neonatal and maternal outcomes for comparable cesarean section rates . We report the maternal health-related quality of life ( HR-QoL ) that was measured alongside the trial at several points in time . Methods Both r and omized and non-r and omized women were asked to participate in the HR-QoL study . Women were asked to fill out written vali date d question naires , covering background characteristics , condition-specific issues and the Short Form ( SF-36 ) , European Quality of Life ( EuroQoL 6D3L ) , Hospital Anxiety and Depression scale ( HADS ) , and Symptom Check List ( SCL-90 ) at baseline , 6 weeks postpartum and 6 months postpartum . We compared the difference scores of all summary measures between the two management strategies by ANOVA . A repeated measures multivariate mixed model was defined to assess the effect of the management strategies on the physical ( PCS ) and mental ( MCS ) components of the SF-36 . Analysis was by intention to treat . Results We analyzed data of 361 r and omized and 198 non-r and omized patients . There were no clinical ly relevant differences between the treatments at 6 weeks or 6 months postpartum on any summary measures ; e.g. , on the SF-36 ( PCS : P = .09 ; MCS : P = .48 ) . The PCS and the MCS were below norm values at inclusion . The PCS improved over time but stayed below norm values at 6 months , while the MCS did not improve . Conclusion In pregnancies complicated by IUGR beyond 36 weeks , induction of labor does not affect the long-term maternal quality of life Background Around 80 % of intrauterine growth restricted ( IUGR ) infants are born at term . They have an increase in perinatal mortality and morbidity including behavioral problems , minor developmental delay and spastic cerebral palsy . Management is controversial , in particular the decision whether to induce labour or await spontaneous delivery with strict fetal and maternal surveillance . We propose a r and omised trial to compare effectiveness , costs and maternal quality of life for induction of labour versus expectant management in women with a suspected IUGR fetus at term . Methods / design The proposed trial is a multi-centre r and omised study in pregnant women who are suspected on clinical grounds of having an IUGR child at a gestational age between 36 + 0 and 41 + 0 weeks . After informed consent women will be r and omly allocated to either induction of labour or expectant management with maternal and fetal monitoring . R and omisation will be web-based . The primary outcome measure will be a composite neonatal morbidity and mortality . Secondary outcomes will be severe maternal morbidity , maternal quality of life and costs . Moreover , we aim to assess neurodevelopmental and neurobehavioral outcome at two years as assessed by a postal enquiry ( Child Behavioral Check List-CBCL and Ages and Stages Question naire-ASQ ) . Analysis will be by intention to treat . Quality of life analysis and a preference study will also be performed in the same study population . Health technology assessment with an economic analysis is part of this so called Digitat trial ( Disproportionate Intrauterine Growth Intervention Trial At Term ) . The study aims to include 325 patients per arm . Discussion This trial will provide evidence for which strategy is superior in terms of neonatal and maternal morbidity and mortality , costs and maternal quality of life aspects . This will be the first r and omised trial for IUGR at term . Trial registration Dutch Trial Register and IS RCT N-Register : IS RCT N10363217 OBJECTIVE To test whether steroids reduce respiratory distress in babies born by elective caesarean section at term . DESIGN Multicentre pragmatic r and omised trial . SETTING 10 maternity units . PARTICIPANTS 998 consenting women r and omised at decision to deliver by elective caesarean section ; 503 r and omised to treatment group . INTERVENTIONS The treatment group received two intramuscular doses of 12 mg betamethasone in the 48 hours before delivery . The control group received treatment as usual . OUTCOME MEASURES The primary outcome was admission to special care baby unit with respiratory distress . Secondary outcomes were severity of respiratory distress and level of care in response . RESULTS Sex , birth weight , and gestation were not different between the two groups . Of the 35 babies admitted to special baby units with respiratory distress , 24 were in the control group and 11 in the intervention group ( P = 0.02 ) . The incidence of admission with respiratory distress was 0.051 in the control group and 0.024 in the treatment group ( relative risk 0.46 , 95 % confidence interval 0.23 to 0.93 ) . The incidence of transient tachypnoea of the newborn was 0.040 in the control group and 0.021 in the treatment group ( 0.54 , 0.26 to 1.12 ) . The incidence of respiratory distress syndrome was 0.011 in the control group and 0.002 in the treatment group ( 0.21 , 0.03 to 1.32 ) . CONCLUSIONS Antenatal betamethasone and delaying delivery until 39 weeks both reduce admissions to special care baby units with respiratory distress after elective caesarean section at term OBJECTIVE The Disproportionate Intrauterine Growth Intervention Trial at Term ( DIGITAT trial ) showed that in women with suspected intrauterine growth restriction ( IUGR ) at term , there were no substantial outcome differences between induction of labour and expectant monitoring . The objective of the present analysis is to evaluate whether maternal or fetal markers could identify IUGR fetuses who would benefit from early labour induction . STUDY DESIGN The DIGITAT trial was a multicenter , parallel and open-label r and omised controlled trial in women who had a singleton pregnancy beyond 36 + 0 weeks ' gestation with suspected IUGR ( n=650 ) . Women had been r and omly allocated to either labour induction or expectant monitoring . The primary outcome was a composite measure of adverse neonatal outcome , defined as neonatal death before hospital discharge , Apgar score < 7 , umbilical artery pH < 7.05 , or admission to neonatal intensive care . Using logistic regression modelling , we investigated associations between outcome and 17 markers , maternal characteristics and fetal sonographic and Doppler velocimetry measurements , all collected at study entry . RESULTS 17 ( 5.3 % ) infants in the induction group had an adverse neonatal outcome compared to 20 ( 6.1 % ) in the expectant monitoring group . The only potentially informative marker for inducing labour was maternal pre-pregnancy body mass index ( BMI ) . Otherwise , we observed at best weak associations between a benefit from labour induction and maternal age , ethnicity , smoking , parity , pregnancy-induced hypertension or preeclampsia , Bishop score and gestational age , or fetal sonographic markers ( gender , estimated fetal weight , body measurements , oligohydramnios , or umbilical artery pulsatility index and end diastolic flow ) . CONCLUSION In late preterm and term pregnancies complicated by suspected intrauterine growth restriction , most of the known prognostic markers seem unlikely to be helpful in identifying women who could benefit from labour induction , except for maternal pre-pregnancy BMI Objective To compare the effect of induction of labour with a policy of expectant monitoring for intrauterine growth restriction near term . Design Multicentre r and omised equivalence trial ( the Disproportionate Intrauterine Growth Intervention Trial At Term ( DIGITAT ) ) . Setting Eight academic and 44 non-academic hospitals in the Netherl and s between November 2004 and November 2008 . Participants Pregnant women who had a singleton pregnancy beyond 36 + 0 weeks ’ gestation with suspected intrauterine growth restriction . Interventions Induction of labour or expectant monitoring . Main outcome measures The primary outcome was a composite measure of adverse neonatal outcome , defined as death before hospital discharge , five minute Apgar score of less than 7 , umbilical artery pH of less than 7.05 , or admission to the intensive care unit . Operative delivery ( vaginal instrumental delivery or caesarean section ) was a secondary outcome . Analysis was by intention to treat , with confidence intervals calculated for the differences in percentages or means . Results 321 pregnant women were r and omly allocated to induction and 329 to expectant monitoring . Induction group infants were delivered 10 days earlier ( mean difference −9.9 days , 95 % CI −11.3 to −8.6 ) and weighed 130 g less ( mean difference −130 g , 95 % CI −188 g to −71 g ) than babies in the expectant monitoring group . A total of 17 ( 5.3 % ) infants in the induction group experienced the composite adverse neonatal outcome , compared with 20 ( 6.1 % ) in the expectant monitoring group ( difference −0.8 % , 95 % CI −4.3 % to 3.2 % ) . Caesarean sections were performed on 45 ( 14.0 % ) mothers in the induction group and 45 ( 13.7 % ) in the expectant monitoring group ( difference 0.3 % , 95 % CI −5.0 % to 5.6 % ) . Conclusions In women with suspected intrauterine growth restriction at term , we found no important differences in adverse outcomes between induction of labour and expectant monitoring . Patients who are keen on non-intervention can safely choose expectant management with intensive maternal and fetal monitoring ; however , it is rational to choose induction to prevent possible neonatal morbidity and stillbirth . Trial registration International St and ard R and omised Controlled Trial number IS RCT N10363217 Objectives : In low-risk pregnancies , the management of oligohydramnios is not clear . The aim of this study was to compare maternal and neonatal outcomes in cases of isolated oligohydramnios r and omised to either induction of labour or expectant management . Methods : 87 women pregnant beyond 40 completed weeks were asked to participate in the study . Fifty-four accepted and were r and omised at 288 days of pregnancy . Twenty-six were r and omised to expectant management and 28 to induction of labour . The primary maternal outcome was the mode of delivery and the primary neonatal outcomes were cord blood pH and Apgar score at delivery . Results : No significant differences were found for any important maternal or neonatal outcome . Conclusion : Based on these results , the decisions about management could be individualised . Even though the number of patients included was small , these results are well in concordance with others The association between a reduction in fetal movements ( RFM ) and stillbirth has been noted for at least 450 years . This was formalised from the 1970s onwards in a series of studies that noted the increased incidence of stillbirth and FGR in women presenting with RFM , which in some cases preceded intrauterine fetal death by several days . Interpretation of the literature relating RFM to stillbirth and FGR is complicated by differences in studies ’ definitions of RFM and FGR [ 1 ] . Nevertheless , the association between RFM and stillbirth remains , irrespective of the definitions used . Recently , the Auckl and Stillbirth Study confirmed that women who had a RFM were 2.4 times ( 95 % CI 1.29 - 4.35 ) more likely to have a late stillbirth [ 2 ] , which is strikingly similar to a UK-based study which found a 3-fold increase in stillbirth after one presentation with RFM [ 3 ] . RFM , FGR and stillbirth are thought to be related by placental insufficiency , with RFM representing fetal compensation to restriction of nutrients and oxygen in utero [ 4,5 ] . This hypothesis is supported by evidence of abnormal placental structure and amino acid transport in women with RFM , even in the absence of a small-for-gestational age fetus [ 6 ] . Despite the association between RFM and stillbirth , RFM is frequently suboptimally managed clinical ly . Of 422 stillbirths review ed in a confidential enquiry , 16.4 % of cases had suboptimal care related to RFM , including : not communicating the importance of RFM to mothers and a failure to act on RFM [ 7 ] . Reasons for clinicians ’ behaviour have been explored by two related question naire studies , one in the UK and one in Australia and New Zeal and . Both of these studies found significant variations in the definitions of RFM applied to clinical practice and varied knowledge of the association between RFM , FGR and stillbirth . As a consequence clinical management of women with RFM varied significantly , with cardiotocography being used in 80 - 90 % of cases and ultrasound assessment of fetal growth , liquor volume and umbilical artery Doppler in approximately 20 % of cases [ 8,9 ] . Due to the association between RFM , FGR and stillbirth , ultrasound assessment of fetal growth , liquor volume and umbilical artery Doppler may be useful screening tests to identify placental insufficiency [ 10 ] . Norwegian studies have suggested that asking women to be more aware of fetal movements did not increase the number of attendances with RFM . Importantly , the implementation of an associated quality -improvement programme was associated with increased use of ultrasound , but a reduction of stillbirth from 4.2 % to 2.4 % [ 11 ] , strongly suggesting that appropriate identification of , and intervention following , RFM may decrease the incidence of stillbirth . The management of RFM may be improved by more sensitive tests to specifically identify placental dysfunction , including measurement of placentally-derived factors such as human placental lactogen or placental growth factor [ 12,13 ] . The use of RFM as a screening tool for stillbirth prevention needs to be developed ; it has the advantages that it is free and does not significantly increase the burden on the antenatal service . However , the best management protocol after women present with RFM has yet to be determined . To date there have been no r and omised controlled trials of the management of RFM , despite calls from the World Health Organisation to improve the quality of evidence regarding stillbirth prevention [ 14 ] . Therefore , a high- quality trial is needed to evaluate whether intervention ( delivery ) directed by appropriate investigations after RFM can reduce the incidence of late stillbirth , without significantly increasing maternal and perinatal morbidity OBJECTIVE The purpose of this study was to compare birth outcomes that result from the active management of risk in pregnancy at term ( AMOR-IPAT ) to those outcomes that result from st and ard management . STUDY DESIGN This was a r and omized clinical trial with 270 women of mixed parity . AMOR-IPAT used preventive labor induction to ensure delivery before the end of an estimated optimal time of delivery . Rates of 4 adverse obstetric events and 2 composite measures were used to evaluate birth outcomes . RESULTS The AMOR-IPAT-exposed group had a similar cesarean delivery rate ( 10.3 % vs 14.9 % ; P = .25 ) , but a lower neonatal intensive care unit admission rate ( 1.5 % vs 6.7 % ; P = .03 ) , a higher uncomplicated vaginal birth rate ( 73.5 % vs 62.8 % ; P = .046 ) , and a lower mean Adverse Outcome Index score ( 1.4 vs 8.6 ; P = .03 ) . CONCLUSION AMOR-IPAT exposure improved the pattern of birth outcomes . Larger r and omized clinical trials are needed to explore further the impact of AMOR-IPAT on birth outcomes and to determine the best methods of preventive labor induction OBJECTIVE To test the hypothesis that in pregnancies with a clinical ly suspected growth restricted foetus at term , induction of labour is as safe as expectant management , and does not lead to increased obstetrical interventions or perinatal morbidity . STUDY DESIGN In one obstetric centre , 33 women with a clinical ly suspected growth restricted foetus at term were r and omly allocated after stratification for parity to either induction or to expectant management . Obstetric and neonatal outcome variables were compared . RESULTS There was a lower gestational age at labour ( median 38(0 ) weeks versus 40(1 ) weeks ) with a corresponding tendency to lower birth weight ( mean 2428 g versus 2651 g ) , and a reduced need for ante partum medical surveillance , in the induction group . No significant differences in obstetrical interventions ( 25 % versus 24 % ) and neonatal morbidity rates ( 50 % versus 35 % ) were found . CONCLUSION A larger multicenter study with a sufficient power and long-term follow-up to decide the best policy for the term growth restricted foetus is feasible OBJECTIVE Pregnancies complicated by intrauterine growth restriction ( IUGR ) are at increased risk for neonatal morbidity and mortality . The Dutch nationwide disproportionate intrauterine growth intervention trial at term ( DIGITAT trial ) showed that induction of labour and expectant monitoring were comparable with respect to composite adverse neonatal outcome and operative delivery . In this study we compare the costs of both strategies . STUDY DESIGN A cost analysis was performed alongside the DIGITAT trial , which was a r and omized controlled trial in which 650 women with a singleton pregnancy with suspected IUGR beyond 36 weeks of pregnancy were allocated to induction or expectant management . Re source utilization was documented by specific items in the case report forms . Unit costs for clinical re sources were calculated from the financial reports of participating hospitals . For primary care costs Dutch st and ardized prices were used . All costs are presented in Euros converted to the year 2009 . RESULTS Antepartum expectant monitoring generated more costs , mainly due to longer antepartum maternal stays in hospital . During delivery and the postpartum stage , induction generated more direct medical costs , due to longer stay in the labour room and longer duration of neonatal high care/medium care admissions . From a health care perspective , both strategies generated comparable costs : on average € 7106 per patient for the induction group ( N=321 ) and € 6995 for the expectant management group ( N=329 ) with a cost difference of € 111 ( 95%CI : € -1296 to 1641 ) . CONCLUSION Induction of labour and expectant monitoring in IUGR at term have comparable outcomes immediately after birth in terms of obstetrical outcomes , maternal quality of life and costs . Costs are lower , however , in the expectant monitoring group before 38 weeks of gestation and costs are lower in the induction of labour group after 38 weeks of gestation . So if induction of labour is considered to pre-empt possible stillbirth in suspected IUGR , it is reasonable to delay until 38 weeks , with watchful monitoring |
13,890 | 28,444,736 | Short-term use of SPRMs result ed in improved quality of life , reduced menstrual bleeding and higher rates of amenorrhoea than were seen with placebo .
Thus , SPRMs may provide effective treatment for women with symptomatic fibroids .
Evidence derived from one RCT showed no difference between leuprolide acetate and SPRM with respect to improved quality of life and bleeding symptoms .
Evidence was insufficient to show whether effectiveness was different between SPRMs and leuprolide .
Investigators more frequently observed SPRM-associated endometrial changes in women treated with SPRMs than in those treated with placebo or leuprolide acetate .
As noted above , SPRM-associated endometrial changes are benign , are not related to cancer and are not precancerous . | BACKGROUND Uterine fibroids are smooth muscle tumours arising from the uterus .
These tumours , although benign , are commonly associated with abnormal uterine bleeding , bulk symptoms and reproductive dysfunction .
The importance of progesterone in fibroid pathogenesis supports selective progesterone receptor modulators ( SPRMs ) as effective treatment .
Both biochemical and clinical evidence suggests that SPRMs may reduce fibroid growth and ameliorate symptoms .
SPRMs can cause unique histological changes to the endometrium that are not related to cancer , are not precancerous and have been found to be benign and reversible .
This review summarises r and omised trials conducted to evaluate the effectiveness of SPRMs as a class of medication for treatment of individuals with fibroids .
OBJECTIVES To evaluate the effectiveness and safety of SPRMs for treatment of premenopausal women with uterine fibroids . | Objective To evaluate the efficacy , safety , and quality of life of 5 mg mifepristone per day compared with a placebo in treating uterine fibroids . Design R and omized , double-blind clinical study . Location Eusebio Hernández Gynecology and Obstetrics Teaching Hospital , Havana , Cuba . Subjects One hundred twenty-four subjects with symptomatic uterine fibroids . Treatment One daily capsule of 5 mg mifepristone or a mifepristone placebo over 3 months . Variables in evaluating safety Changes in fibroid and uterine volumes , changes in symptom prevalence and intensity , and changes in quality of life . Results Three months into treatment , fibroid volume was reduced by 28.5 % in the mifepristone group with an increase of 1.8 % in the placebo group ( P = 0.031 ) . There were significant differences between the groups with respect to pelvic pain prevalence ( P = 0.006 ) , pelvic pressure ( P = 0.027 ) , rectal pain ( P = 0.013 ) , hypermenorrhea ( P < 0.001 ) , and metrorrhagia ( P = 0.002 ) at the end of treatment . Amenorrhea was 93.1 % and 4.3 % in the mifepristone and placebo groups , respectively ( P < 0.001 ) . Treatment side effects were significantly greater in the mifepristone group . Estradiol levels did not differ significantly between the placebo and mifepristone groups at the end of treatment . Improvement in quality of life was significantly greater in the categories of “ symptoms ” ( P = 0.004 ) and “ activity ” ( P = 0.045 ) in the mifepristone group . Conclusion The 5 mg dosage of mifepristone presented significantly superior efficacy compared to the placebo BACKGROUND The efficacy and side-effect profile of ulipristal acetate as compared with those of leuprolide acetate for the treatment of symptomatic uterine fibroids before surgery are unclear . METHODS In this double-blind noninferiority trial , we r and omly assigned 307 patients with symptomatic fibroids and excessive uterine bleeding to receive 3 months of daily therapy with oral ulipristal acetate ( at a dose of either 5 mg or 10 mg ) or once-monthly intramuscular injections of leuprolide acetate ( at a dose of 3.75 mg ) . The primary outcome was the proportion of patients with controlled bleeding at week 13 , with a prespecified noninferiority margin of -20 % . RESULTS Uterine bleeding was controlled in 90 % of patients receiving 5 mg of ulipristal acetate , in 98 % of those receiving 10 mg of ulipristal acetate , and in 89 % of those receiving leuprolide acetate , for differences ( as compared with leuprolide acetate ) of 1.2 percentage points ( 95 % confidence interval [ CI ] , -9.3 to 11.8 ) for 5 mg of ulipristal acetate and 8.8 percentage points ( 95 % CI , 0.4 to 18.3 ) for 10 mg of ulipristal acetate . Median times to amenorrhea were 7 days for patients receiving 5 mg of ulipristal acetate , 5 days for those receiving 10 mg of ulipristal acetate , and 21 days for those receiving leuprolide acetate . Moderate-to-severe hot flashes were reported for 11 % of patients receiving 5 mg of ulipristal acetate , for 10 % of those receiving 10 mg of ulipristal acetate , and for 40 % of those receiving leuprolide acetate ( P<0.001 for each dose of ulipristal acetate vs. leuprolide acetate ) . CONCLUSIONS Both the 5-mg and 10-mg daily doses of ulipristal acetate were noninferior to once-monthly leuprolide acetate in controlling uterine bleeding and were significantly less likely to cause hot flashes . ( Funded by PregLem ; Clinical Trials.gov number , NCT00740831 . ) Clinical trials , systematic review s , and guidelines compare beneficial and non-beneficial outcomes following interventions . Often , however , various studies on a particular topic do not address the same outcomes , making it difficult to draw clinical ly useful conclusions when a group of studies is looked at as a whole.1 This problem was recently thrown into sharp focus by a systematic review of interventions for preterm birth prevention , which found that among 103 r and omized trials , no fewer than 72 different outcomes were reported.2 There is a growing recognition among clinical research ers that this variability undermines consistent synthesis of the evidence , and that what is needed is an agreed st and ardized collection of outcomes —a “ core outcomes set”—for all trials in a specific clinical area.1 Recognizing that the current inconsistency is a serious hindrance to progress in our specialty , the editors of over 50 journals related to women ’s health have come together to support The CROWN ( CoRe Outcomes in WomeN ’s health ) Initiative ( ► Table 1 ) . Development of consensus is required around a set of welldefined , relevant , and feasible outcomes for all trials concerning particular obstetric and gynaecologic health conditions , such as preterm birth , incontinence , infertility , and menstrual problems . With somany subspecialties involved , this is no easy task . Duplication of effort can be avoided by working with the Core Outcome Measures in Effectiveness Trials ( COMET ) Initiative , which is working toward core data sets for all medical specialties.3 Production of trustworthy core outcome sets will require engagement with patients , healthcare professionals , research ers , industry , and regulators , and the employment of scientifically robust consensus methods .1 The data for these core outcome sets , once agreed upon , should be collected in trials and reported in publications as st and ard practice in the future . Journal editors now invite research ers to take the lead in beginning this work . What will we do as editors to support them and their colleagues ? First , we are drawing wide attention toThe CROWN Initiative by publishing this editorial in the journals listed below . We shall ensure that the global research community , which includes our many review ers , is aware of the need for core outcome sets . Su bmi ssions which describe development of core outcome sets , if deemed acceptable after peer review , will be effectively disseminated . Our collaboration is not for enforcing harmony at the expense of innovation . To quote from the COMET home page ( www.comet-initiative.org ) : “ The existence or use of a core outcome set does not imply that outcomes in a particular trial should be restricted to those in the relevant core outcome set . Rather , there is an expectation that the core outcomes will be collected and reported , making it easier for the results of trials to be compared , contrasted and combined as appropriate ; while research ers continue to explore other outcomes as well . ” We also expect that as new or superior ways of capturing outcomes emerge , core outcome sets will themselves need updating . Table 1 Aims of The CROWN Objectives The aim of this study was to evaluate the safety and improvement in quality of life using 10 mg and 5 mg daily doses of mifepristone for the treatment of uterine fibroids . Design The research was a r and omized double-blind clinical study undertaken at the Eusebio Hernández Hospital in Havana , Cuba . Subjects and methods Seventy subjects with symptomatic uterine fibroids took one daily capsule of 10 mg or 5 mg mifepristone orally for 9 months . One to three endometrial biopsies were performed . In evaluating safety , the variables studied were endometrial changes associated with mifepristone , elevation of hepatic transaminases , side effects of mifepristone , and instances and duration of irregular bleeding . Results There were 30/49 ( 61.2 % ) and 13/24 ( 54.2 % ) diagnoses of endometrial changes associated with mifepristone in the 10 mg and 5 mg groups , respectively ( P = 0.282 ) . At every evaluation visit the average endometrial thickness was significantly greater in the 10 mg group than in the 5 mg group ( P = 0.013 , P = 0.002 , and P = 0.013 , respectively ) . Only five subjects had slight elevations in their hepatic transaminases after 9 months ’ treatment . Sixteen of 35 ( 45.7 % ) and eight of 33 ( 24.2 % ) subjects had the occasional hot flush in the 10 mg and 5 mg groups , respectively ( P = 0.032 ) . In total , there were 12.9 ± 4.6 ( n = 21 ) and 9.1 ± 3.9 ( n = 18 ) days of irregular bleeding in the 10 mg and 5 mg groups , respectively ( P = 0.009 ) . Conclusion According to the study findings , a 5 mg daily dose over 9 months has a relatively better safety profile than the 10 mg dose OBJECTIVE : To estimate the efficacy of daily administration of 5 mg compared with 10 mg of mifepristone for the treatment of uterine myomas . METHODS : One hundred women were r and omly assigned to receive oral mifepristone 5 mg or 10 mg daily for 3 months ( 50 per group ) . Abdominal ultrasonography was performed before treatment , at 45 days , and at 3 months to evaluate leiomyoma and uterine volumes . Endometrial biopsy specimens were taken before and after treatment . Efficacy was estimated by the reduction percentages of the leiomyoma and uterine volumes . RESULTS : After 90 days treatment there was a 45 % ( 95 % confidence interval [ CI ] 37–54 , P<.001 ) and a 57 % ( 95 % CI 48–67 , P<.001 ) reduction in the leiomyoma volume in the 10-mg and 5-mg groups , respectively , and one of 40 % ( 95 % CI 34–46 , P=.002 ) , and 36 % ( 95 % CI 31–40 , P<.001 ) , respectively , in the uterine volume . Symptomatic improvement was noted , and the prevalence of symptoms diminished significantly . There were no significant differences in reduction of volume and symptoms in the treatment groups , P>.05 in all cases . After treatment , 44 of 49 ( 89.8 % ) women from the mifepristone 10 mg group and 45 of 50 ( 90.0 % ) from the 5-mg group , respectively , were amenorrheic ( P=.487 ) . Endometrial biopsy after treatment showed simple hyperplasia in 1 of 50 ( 2.0 % ) in the mifepristone 10 mg group . CONCLUSION : Five-milligram doses of mifepristone produce reductions in leiomyoma and uterine volumes and symptomatic improvement similar to 10-mg doses . LEVEL OF EVIDENCE : OBJECTIVE Our purpose was to examine the effects of RU 486 and leuprolide acetate on uterine artery blood flow and uterine volume . STUDY DESIGN Patients were r and omly assigned to group A ( eight patients ) receiving 25 mg of RU 486 daily for 3 months or group B ( six patients ) receiving 3.75 mg of leuprolide acetate monthly for 3 months . Uterine artery blood flow change was determined by resistive index by means of vaginal color Doppler ultrasonography . Uterine volume was measured before and during the study with abdominal ultrasonography . RESULTS Both groups showed an increase in resistive index . Patients receiving RU 486 had uterine artery blood flow decreased by 40 % , and those receiving leuprolide acetate had a 21 % decrease . We noted a significant decrease in uterine volume compared with pretreatment in both groups at 3 months . There was no significant decrease between groups . CONCLUSION Both RU 486 ( 25 mg daily ) and leuprolide acetate ( 3.75 mg monthly ) are effective in decreasing blood flow to the uterus ( increasing resistive index ) and decreasing uterine volume at 3 months . A significant decrease in uterine artery blood flow may provide a mechanism for the decrease in uterine size and the decrease in uterine blood loss at the time of surgery Background & objectives : Uterine myoma is a common indication for hysterectomy in India . An effective medical treatment option may reduce hysterectomy associated morbidity . This study was undertaken to evaluate efficacy and safety of low dose mifepristone in medical management of myoma and to compare two doses - 10 vs. 25 mg/day . Methods : In this r and omized clinical trial , women with symptomatic myoma or myoma>5 cm were included . Uterine size > 20 wk , fibroids > 15 cm were excluded . Pictorial blood loss assessment chart ( PBAC ) score was used to assess menstrual-blood-loss and visual analog scale ( VAS ) for other symptoms . Haemogram , liver function test , ultrasound with doppler and endometrial histology was performed . Patients were r and omized and were given oral mifepristone as 25 mg/day in group 1 and 10 mg/day in group 2 for 3 months . Patients were followed at 1 , 3 and 6 months . Results : Seventy patients in group 1 and 73 in group 2 completed treatment . Mean PBAC score reduced from 253 to 19.8 and from 289.2 to 10.4 at 1 and 3 months in groups 1 and 2 , respectively . At 3 months , 67 of 70 ( 95.7 % ) patients of group 1 and 66 of 73 ( 90.4 % ) of group 2 developed amenorrhoea which reverted after median 34 ( range 4 - 85 ) days . Mean myoma volume decreased by 35.7 per cent ( from 176.8 to 113.7cm3 ) and 22.5 per cent ( from 147.6 to 114.4 cm3 ) at 3 months in groups 1 and 2 , respectively . Side effects seen were leg cramps in 7 of 70 ( 10 % ) and 5 of 73 ( 6.8 % ) and hot-flushes in 5 of 70 ( 7.1 % ) and 5 of 73 ( 6.8 % ) in groups 1 and 2 , respectively . Repeat endometrial-histopathology did not reveal any complex hyperplasia or atypia in either group . Interpretation & conclusions : Mifepristone ( 10 and 25 mg ) caused symptomatic relief with more than 90 per cent reduction in menstrual blood . Greater myoma size reduction occured with 25 mg dose . Amenorrhoea was developed in 90 - 95 per cent patients which was reversible . It can be a reasonable choice for management of uterine leiomyoma as it is administered orally , cost-effective and has mild side effects OBJECTIVE To evaluate the efficacy and tolerability of the P receptor modulator CDB-2914 ( Ulipristal , CDB ) . DESIGN R and omized , placebo-controlled double-blind clinical trial . SETTING Clinical research center . PATIENT(S ) Premenopausal women with symptomatic uterine fibroids . INTERVENTION(S ) Once-daily oral CDB ( 10 or 20 mg ) or placebo ( PLC ) for 12 weeks ( treatment 1 ) . A second 3-month treatment with CDB ( treatment 2 ) was offered . A computer-generated blocked r and omization was used . MAIN OUTCOME MEASURE(S ) Magnetic resonance imaging (MRI)-determined total fibroid volume ( TFV ) change was the primary outcome ; amenorrhea and quality of life ( QOL ) were secondary end points . RESULT ( S ) Treatment 1 TFV increased 7 % in the PLC group , but decreased 17 % and 24 % in the CDB10 and CDB20 groups . The TFV decreased further in treatment 2 ( -11 % ) . Amenorrhea occurred in 20/26 women taking CDB and none on PLC . Ovulation resumed after CDB . Hemoglobin improved only with CDB ( 11.9 ± 1.5 to 12.9 ± 1.0 g/dL ) as did the Fibroid QOL Question naire symptom severity , energy/mood , and concern subscores , and overall QOL scores . The CDB was well tolerated , with no serious adverse events . Adverse events were unchanged during treatments . CONCLUSION ( S ) Administration of CDB-2914 for 3 - 6 months controls bleeding , reduces fibroid size , and improves QOL OBJECTIVE To investigate the efficacy and safety of repeated 12-week courses of 5 or 10 mg daily of ulipristal acetate for intermittent treatment of symptomatic uterine fibroids . DESIGN Double-blind , r and omized administration of two 12-week courses of ulipristal acetate . SETTING Gynecology centers . PATIENT(S ) A total of 451 patients with symptomatic uterine fibroid(s ) and heavy bleeding . INTERVENTION(S ) Two repeated 12-week treatment courses of daily 5 or 10 mg of ulipristal acetate . MAIN OUTCOME MEASURE(S ) Amenorrhea , controlled bleeding , fibroid volume , quality of life ( QoL ) , pain . RESULT ( S ) In the 5- and 10-mg treatment groups ( 62 % and 73 % of patients , respectively ) achieved amenorrhea during both treatment courses . Proportions of patients achieving controlled bleeding during two treatment courses were > 80 % . Menstruation resumed after each treatment course and was diminished compared with baseline . After the second treatment course , median reductions from baseline in fibroid volume were 54 % and 58 % for the patients receiving 5 and 10 mg of ulipristal acetate , respectively . Pain and QoL improved in both groups . Ulipristal acetate was well tolerated with less than 5 % of patients discontinuing treatment due to adverse events . CONCLUSION ( S ) Repeated 12-week courses of daily oral ulipristal acetate ( 5 and 10 mg ) effectively control bleeding and pain , reduce fibroid volume , and restore QoL in patients with symptomatic fibroids . CLINICAL TRIAL REGISTRATION NUMBER NCT01629563 ( PEARL IV ) RESEARCH QUESTION What is the individualized bleeding experience of women with fibroids and anaemia in a 3 month r and omized placebo controlled trial ( PEARL I ) of the selective progesterone receptor modulator ( SPRM ) , ulipristal acetate ( UPA ) ? SUMMARY ANSWER In contrast to continuing excessive regular menstruation in the placebo group , a majority of women treated with UPA ( 63.1 % of those on 5 mg/day and 71.3 % of those on 10 mg/day ) experienced the rapid onset of amenorrhoea or minimal blood loss [ pictorial blood loss assessment chart ( PBAC ) < 12 ] . The remainder experienced various patterns of bleeding and intensity of blood loss that are described for the first time , including an association of irregular bleeding on UPA with sub-mucous fibroids . WHAT IS KNOWN ALREADY The majority experience on UPA is amenorrhoea but the bleeding experience of the others has not been characterized . STUDY DESIGN , SIZE , DURATION A 13 week r and omized controlled trial in women , eligible for surgery for uterine fibroids and anaemia , comparing placebo ( n = 48 ) , UPA 5 mg ( n = 95 ) or UPA 10 mg ( n = 94 ) . The treatment aim was fibroid shrinkage and the primary definitions and outcomes are published elsewhere ; here the secondary outcome measure of vaginal bleeding pattern is described . PARTICIPANTS / MATERIAL S , SETTING , METHODS Women , 18 - 50 years old , with fibroids and haemoglobin ≤10.2 g/dl , justifying surgery . At least one fibroid was 3 - 10 cm diameter and uterus ≤16 weeks pregnancy size . All used the daily PBAC methodology in a screening cycle ( Ps ) and throughout treatment , and for the 4 weeks preceding Week 26 and Week 38 in those who did not have surgery . An excessive menstruation is PBAC > 100 . The bleeding patterns were characterized using the classification of Belsey , developed under auspices of WHO . MAIN RESULTS AND THE ROLE OF CHANCE In the placebo group , all women had an excessive screening PBAC [ median 376 ; interquartile range ( IQR ) 241 - 574 ] ; 81.3 % of them had regular menstrual bleeding and the intensity of bleeding remained similar , so that the median PBAC in the next three periods was 90 , 92 and 93 % of the screening value . Four of the 48 women had spontaneous improvement in bleeding and one developed amenorrhoea and elevation of gonadotrophins . In the placebo group , 22 women provided Week 26 and 21 women provided Week 38 PBAC data . The median Week 26 PBAC ( 312 : IQR 102 - 524 ) and Week 38 PBAC ( 236 ; IQR 103 - 465 ) indicated ongoing excessive bleeding . In the UPA group , screening PBAC confirmed excessive bleeding ( UPA 5 mg , median 358 ; IQR 232 - 621 ; UPA 10 mg , median 330 ; IQR 235 - 542 ) . UPA was initiated from the start of a menstruation ( P1 ) and no women had regular periods on treatment . Following P1 through the whole of the remaining 13 weeks of UPA treatment amenorrhoea or minimal loss ( PBAC < 12 for whole phase ) occurred in 63.1 % ( UPA 5 mg ) or 71.3 % ( UPA 10 mg ) . The characterization of the individualized bleeding experience of the remaining women on 5 mg and 10 mg UPA , respectively , were infrequent bleeding in 17.9 and 12.8 % ; frequent or prolonged bleeding or both in 12.7 and 11.7 % and irregular bleeding in 5.3 and 3.2 % . In those with prolonged , frequent or irregular bleeding there was a high chance that sub-mucous fibroids were present ( UPA 5 mg 100 % and UPA 10 mg 78.6 % ) but no correlation with progesterone receptor modulator-associated endometrial changes . LIMITATIONS , REASONS FOR CAUTION The follow-up PBAC data at Week 26 and Week 38 are only valid for women who did not have surgical intervention . These groups may not be representative of the groups at screening . WIDER IMPLICATION S OF THE FINDINGS This first detailed description of these SPRM bleeding patterns provides clinicians with an indication of potential responses in women using the SPRM UPA and provides an extended definition of bleeding in untreated women with excessive bleeding and fibroids . STUDY FUNDING /COMPETING INTEREST(S ) Funded by PregLem/Gedeon Richter . D.H.B. is a member of the Scientific Advisory Board of PregLem , and in this role participated in the study design and supervision . Stock originally held in PregLem was given up when PregLem was incorporated into Gedeon Richter ; D.H.B. does not currently hold stock . M.A.L. has received payment from Gideon Richter to attend a meeting to present these data ( Barcelona , April 2013 ) but no financial support in preparing the manuscript . B.C.J.M.F. is a member of the Scientific Advisory Board of PregLem and has received fees and grant support from the following companies : And romed , Ardana , Auxogyn , Ferring , Genovum , Gedeon Richter , Merck Serono , MSD , Organon , Pantharei Bioscience , PregLem , Roche , Schering , Schering Plough , Serono , Watson Laboratories and Wyeth . P.T. is a paid statistical consultant for PregLem SA . E.B. is a full time employee of PregLem and received payment from stocks sold in October 2010 from the company 's full acquisition by Gedeon Richter Group . TRIAL REGISTRATION NUMBER Clinical Trials.gov Identifier : NCT00755755 ( PEARL I ) Objectives To evaluate the efficacy and safety of 2.5 mg and 5 mg mifepristone during 3 months for the treatment of uterine fibroids before surgery . Design Multicenter r and omized clinical trial . Locations Eusebio Hernández Hospital , Havana , Cuba and the Alemán Hospital , Managua , Nicaragua . Subjects Included in the study were 146 women with symptomatic uterine fibroids . Treatment Group I : half a tablet of 5 mg ( 2.5 mg ) mifepristone taken orally every 24 hours , and Group II : one tablet of 5 mg mifepristone taken orally every 24 hours over a period of 3 months in both groups . Two endometrial biopsies were performed . Variables to evaluate efficacy Increase in average hemoglobin , changes in fibroid and uterine volume , and symptomatic improvement . Results The average hemoglobin at the end of treatment was 0.6 g/dL greater in the 5 mg mifepristone group ( P = 0.033 ) . In both groups there were similar reductions in fibroid volumes . Clinical improvement was more significant in the 5 mg group . Conclusion The dose to be used should be 5 mg In a prior r and omized controlled study , patients treated with ulipristal acetate ( UPA ) or placebo for 3 months had a decrease in leiomyoma size . A total of 10 patients ’ tissue sample s ( 5 placebo and 5 treated with 10 mg/d UPA ) that underwent hysterectomy and tissue preservation were identified from this study . Quantitative real-time reverse transcriptase polymerase chain reaction and Western blotting were used to assess fold gene and protein expression of extracellular membrane ( ECM ) proteins : collagen 1A ( COL1A ) , fibronectin ( FN1 ) , and versican ( VCAN ) of the sample s. Confirmatory immunohistochemical analysis was performed . Changes in total matrix collagen were examined using Masson trichrome staining . Multiplex measurement of the matrix metalloproteinases ( MMPs ) and tissue inhibitor of metalloproteinases was performed . Compared to placebo-treated surgical specimens , 80 % of the treated specimens showed decrease in VCAN protein , 60 % showed decrease in FN1 , but no consistent alteration in COL1A . This effect was also supported by immunohistochemistry where leiomyoma surgical specimens demonstrated decreased amount of FN1 and VCAN on UPA treatment . Increased MMP2 and decreased MMP9 in treated patient leiomyomas indicate both degradation of the matrix and inhibition of the pathway involved in matrix production . Treatment with UPA decreased fibroid volume in placebo-controlled , r and omized trials . Treatment with UPA decreased gene expression and protein production in leiomyoma tissue , suggesting both an impact on water content and ECM protein concentration as a mechanism of ulipristal-mediated decrease in leiomyoma size OBJECTIVE : To evaluate whether 3-month administration of CDB-2914 , a selective progesterone receptor modulator , reduces leiomyoma size and symptoms . METHODS : Premenopausal women with symptomatic uterine leiomyomata were r and omly assigned to CDB-2914 at 10 mg ( T1 ) or 20 mg ( T2 ) daily or to placebo ( PLC ) for 3 cycles or 90–102 days if no menses occurred . The primary outcome was leiomyoma volume change determined by magnetic resonance imaging at study entry and within 2 weeks of hysterectomy . Secondary outcomes included the proportion of amenorrhea , change in hemoglobin and hematocrit , ovulation inhibition , and quality -of-life assessment . RESULTS : Twenty-two patients were allocated , and 18 completed the trial . Age and body mass index were similar among groups . Leiomyoma volume was significantly reduced with CDB-2914 administration ( PLC 6 % ; CDB-2914 –29 % ; P=.01 ) , decreasing 36 % and 21 % in the T1 and T2 groups , respectively . During treatment , hemoglobin was unchanged , and the median estradiol was greater than 50 pg/mL in all groups . CDB-2914 eliminated menstrual bleeding and inhibited ovulation ( % ovulatory cycles : CDB-2914 , 20 % ; PLC , 83 % ; P=.001 ) . CDB-2914 improved the concern scores of the uterine leiomyoma symptom quality -of-life subscale ( P=.04 ) . One CDB-2914 woman developed endometrial cystic hyperplasia without evidence of atypia . No serious adverse events were reported . CONCLUSION : Compared with PLC , CDB-2914 significantly reduced leiomyoma volume after three cycles , or 90–102 days . CDB-2914 treatment result ed in improvements in the concern subscale of the Uterine Fibroid Symptom Quality of Life assessment . In this small study , CDB-2914 was well-tolerated without serious adverse events . Thus , there may be a role for CDB-2914 in the treatment of leiomyomata . Clinical Trial Registration : Clinical Trials.gov , www . clinical trials.gov , NCT00290251 LEVEL OF EVIDENCE : BACKGROUND Uterine leiomyomas are widely prevalent and frequently cause menorrhagia . The major therapeutic option today is hysterectomy . Medical options are of highest interest . METHODS A total of 30 women with uterine leiomyomas scheduled for surgical intervention were r and omized to receive either 50 mg mifepristone or placebo every other day during 3 months prior to surgery . Uterine blood flow and leiomyoma volume were evaluated once a month until surgery . Endometrial biopsies were obtained prior to and at end of treatment . Relevant biochemistry , symptoms and bleeding were recorded . Primary outcome was reduction in uterine leiomyoma size . RESULTS There was a significant percentual decrease ( P = 0.021 ) in the total leiomyoma volume in the mifepristone-treated group , -28 ( -48 , -8 ) % ( mean + /- 0 , 95 confidence interval ) , compared with the control group values 6 ( -13 , 25 ) % . Mifepristone treatment significantly reduced the bleeding days ( P = 0.001 ) and increased serum haemoglobin values ( P = 0.046 ) . Serum cortisol levels remained unchanged , while a mild increase in serum and rogens was noted . Endometrial biopsies showed no premalignant changes or changes in mitotic indices . CONCLUSION Mifepristone may offer an effective treatment option for women with uterine leiomyoma and the associated pronounced uterovaginal bleeding . Clinical Trials identifier : www . clinical trials.gov : NCT00579475 Objectives . To evaluate the efficacy , safety , and quality of life by using 2.5 and mifepristone 5 mg daily doses to treat uterine fibroids over 3 months with a 9-month followup period . Design . R and omized clinical trial . Place . “ Eusebio Hernández ” Hospital , Havana , Cuba . Subjects . 220 women with symptomatic uterine fibroids . Treatment . One-half ( 2.5 mg ) or one-whole 5 mg mifepristone tablet . Variables to Evaluate Efficacy . Changes in fibroid and uterine volumes , in symptomatic prevalence and intensity , and in quality of life . Results . After 3-month treatment , fibroid volume decreased by 27.9 % ( CI 95 % 20–35 ) and 45.5 % ( CI 95 % 37–62 ) , in the 2.5 and 5 mg groups , respectively , P = 0.003 . There was no difference in the prevalence of symptoms at the end of treatment , unlike after 6- and 9-month followup when there was a difference . Amenorrhea was significantly higher in the 5 mg group , P = 0.001 . There were no significant differences in mifepristone side effects between the groups . Both groups displayed a similar improvement in quality of life . Conclusions . The 2.5 mg dosage result ed in a lesser reduction in fibroid size but a similar improvement in quality of life when compared to the 5 mg dose . This trial is registered with Clinical Trials.gov NCT01786226 BACKGROUND The selective progesterone receptor modulator asoprisnil suppresses uterine bleeding and decreases leiomyoma volume while maintaining follicular phase estrogen concentrations . For safety of potential clinical applications , any proliferative effect of asoprisnil on uterine tissues , particularly endometrium , needs to be established . METHODS In a double-blind , r and omized , placebo-controlled study ( continuation of previously published trial No. NCT00150644 ( Williams et al. , 2007 and Wilkens et al. , 2008 ) ) , 33 patients with symptomatic uterine leiomyomata received placebo , 10 or 25 mg asoprisnil daily for 12 weeks before hysterectomy . Proliferation markers Ki-67 and anti-phospho-histone H3 ( PH3 ) were immunolocalized in endometrium , myometrium and leiomyoma tissue . Endometrial PTEN ( phosphatase and tensin homologue , a tumour suppressor gene ) expression was also assessed by immunohistochemistry . PH3-positive gl and ular and stromal cells were counted per measured endometrial area . Endometrial Ki-67 expression was assessed using stereological methods . Stained myometrial and leiomyoma cells were counted per 10 fields ( x250 ) . PTEN immunostaining was quantified using a histoscore . Each asoprisnil group was compared with placebo ( secretory phase ) with significance at 0.05 level . RESULTS Endometrial epithelial proliferation and PTEN expression were not significantly different between placebo and asoprisnil groups . Decreased stromal Ki-67 expression ( P < 0.05 ) suggested any effect of asoprisnil on endometrial proliferation to be inhibitory . Immunolocalization of PTEN expression was not different between treatment groups in any tissue compartments . Myometrial Ki-67 expression decreased following asoprisnil 25 mg ( P < 0.05 ) . CONCLUSIONS Asoprisnil does not induce proliferation of uterine tissues and does not suppress endometrial PTEN expression OBJECTIVE Uterine leiomyoma , or fibroid tumors , are the leading indication for hysterectomy in the United States , but the proportion of women in whom fibroid tumors develop is not known . This study screened for fibroid tumors , independently of clinical symptoms , to estimate the age-specific proportion of black and white women in whom fibroid tumors develop . STUDY DESIGN R and omly selected members of an urban health plan who were 35 to 49 years old participated ( n = 1364 women ) . Medical records and self-report were used to assess fibroid status for those women who were no longer menstruating ( most of whom had had hysterectomies ) . Premenopausal women were screened by ultrasonography . We estimated the age-specific cumulative incidence of fibroid tumors for black and white women . RESULTS Thirty-five percent of premenopausal women had a previous diagnosis of fibroid tumors . Fifty-one percent of the premenopausal women who had no previous diagnosis had ultrasound evidence of fibroid tumors . The estimated cumulative incidence of tumors by age 50 was > 80 % for black women and nearly 70 % for white women . The difference between the age-specific cumulative incidence curves for black and white women was highly significant ( odds ratio , 2.9 ; 95 % CI , 2.5 - 3.4 ; P < .001 ) . CONCLUSION The results of this study suggest that most black and white women in the United States develop uterine fibroid tumors before menopause and that uterine fibroid tumors develop in black women at earlier ages than in white women OBJECTIVE To discuss the mechanism of action of selective progesterone receptor modulators ( SPRMs ) and summarize the pre clinical and clinical efficacy and safety data supporting the potential use of these compounds for gynecologic indications . DESIGN Relevant publications from 2005 onward were identified using a PubMed search . Additional relevant articles were identified from citations within these publications . SETTING None . PATIENT(S ) None . INTERVENTION(S ) None . MAIN OUTCOME MEASURE(S ) None . RESULT ( S ) Mifepristone was first developed as a progesterone receptor antagonist and licensed for pregnancy termination because of the unique property of this compound to terminate pregnancy when associated with prostagl and ins . Then SPRMs were developed , and among those ulipristal acetate , an efficient emergency contraceptive . Because SPRMs effectively inhibit endometrial proliferation and reduce endometriotic lesions in animal models , this suggests a possible role in the treatment of endometriosis in humans . Finally , a number of double-blind , r and omized , placebo-controlled trials have demonstrated the efficacy of asoprisnil , mifepristone , telapristone acetate , and ulipristal acetate in reducing leiomyoma and uterine volume , and suppressing bleeding in women with uterine fibroids . CONCLUSION ( S ) Mifepristone in combination with prostagl and ins has been licensed for pregnancy termination because of its unique ability is this area . Ulipristal acetate is available for emergency contraception . Several SPRMs hold further promise as an effective medical therapy for patients suffering from endometriosis and leiomyoma Objective : The menstrual pictogram ( MP ) , a semiquantitative , easy-to-use tool to assess blood loss , was vali date d against the reference st and ard of alkaline hematin ( AH ) quantitation using data pooled from 3 clinical trials . Methods : Premenopausal women aged ≥18 years with heavy menstrual bleeding ( HMB ) associated with uterine leiomyomata were r and omized to asoprisnil ( 10 or 25 mg ) or placebo . Patients completed the MP and collected feminine hygiene products for assessment of blood loss by the AH method . Agreement between the MP and the AH method was calculated . Results : The positive predictive value of the MP total to distinguish women with HMB against the AH total was 91 % . The agreement ( κ-statistic ) between AH and MP totals for classifying patients with ≥50 % or < 50 % decreases in HMB was 0.88 ( 95 % confidence interval [ CI ] , 0.78 - 0.98 ) , and the MP was 96 % sensitive and 92 % specific . The methods showed good association for percentage change in blood ( intraclass correlation coefficient [ ICC ] of 0.86 , 95 % CI , 0.80 - 0.91 ) but not for actual blood loss per cycle ( ICC of 0.64 , [ 95 % CI , 0.55 - 0.71 ] ) ; the greatest underestimation occurred for severely stained napkins . Conclusion : In this study , the MP distinguished women with HMB and adequately assessed improvements with therapy OBJECTIVE To investigate the efficacy and safety of ulipristal acetate ( UPA ) for long-term treatment of symptomatic uterine fibroids . DESIGN Repeated intermittent open-label UPA courses , each followed by r and omized double-blind norethisterone acetate ( NETA ) or placebo . SETTING European clinical gynecology centers . PATIENT(S ) Two hundred and nine women with symptomatic fibroids including heavy menstrual bleeding . INTERVENTION(S ) Patients received up to four 3-month courses of UPA 10 mg daily , immediately followed by 10-day double-blind treatment with NETA ( 10 mg daily ) or placebo . MAIN OUTCOME MEASURE(S ) Amenorrhea , fibroid volume , endometrial histology . RESULT ( S ) After the first UPA course , amenorrhea occurred in 79 % of women , with median onset ( from treatment start ) of 4 days ( interquartile range , 2 - 6 days ) . Median fibroid volume change was -45 % ( interquartile range , -66 % ; -25 % ) . Amenorrhea rates were 89 % , 88 % , and 90 % for the 131 , 119 , and 107 women who received treatment courses 2 , 3 , and 4 , respectively . Median times to amenorrhea were 2 , 3 , and 3 days for treatment courses 2 , 3 , and 4 , respectively . Median fibroid volume changes from baseline were -63 % , -67 % , and -72 % after treatment courses 2 , 3 , and 4 , respectively . All endometrial biopsies showed benign histology without hyperplasia ; NETA did not affect fibroid volume or endometrial histology . CONCLUSION ( S ) Repeated 3-month UPA courses effectively control bleeding and shrink fibroids in patients with symptomatic fibroids . CLINICAL TRIAL REGISTRATION Clinical Trials.gov ( www . clinical trials.gov ) registration numbers NCT01156857 ( PEARL III ) and NCT01252069 ( PEARL III extension ) OBJECTIVE To develop and vali date a simple method of measuring total menstrual blood loss using a pictorial representation of blood loss , the menstrual pictogram . DESIGN A prospect i ve evaluation of total menstrual blood loss measurement by the menstrual pictogram compared to the alkaline hematin technique . SETTING Academic menorrhagia research clinic . PATIENT(S ) One hundred twenty-one women ; 62 women complaining of heavy menstrual blood loss , 59 women who considered their menstrual blood loss to be normal . INTERVENTION(S ) Participants were asked to complete the menstrual pictogram through the period and collect their feminine hygiene products for an alkaline hematin assessment . MAIN OUTCOME MEASURE(S ) Percentage agreement between blood loss measured by the gold st and ard alkaline hematin method and the menstrual pictogram . Extraneous blood loss was measured using a semiquantitative pictorial method . RESULT ( S ) The menstrual pictogram had a high level of agreement for blood collected on feminine hygiene products compared with the alkaline hematin method . Some women also lose a significantly large amount of extraneous blood , which is not proportional to the alkaline hematin blood loss assessment . CONCLUSION ( S ) The menstrual pictogram provides a simple means of measuring menstrual blood loss . It is no longer appropriate to ignore extraneous blood loss , particularly as there is no correlation between extraneous blood loss and that measured on feminine hygiene products BACKGROUND Asoprisnil is a selective progesterone receptor modulator with mixed progesterone agonist/antagonist activity which controls uterine bleeding via an endometrial effect . This study examined full-thickness endometrial , leiomyoma and myometrial morphology in hysterectomy specimens from patients with uterine leiomyomata , after treatment with asoprisnil for 3 months . METHODS In this double-blind , r and omized , placebo-controlled study , 33 subjects with uterine leiomyomata were r and omized to receive asoprisnil 10 , 25 mg or placebo for an average of 95 days prior to hysterectomy . Sample s of endometrium , myometrium and leiomyoma tissue were subjected to systematic morphological assessment with quantification of mitotic activity . RESULTS In patients treated with 10 or 25 mg asoprisnil , a unique pattern called ' non-physiologic secretory effect ' was evident in endometrium , recognizable through partially developed secretory gl and ular appearances and stromal changes . Endometrial thickness was decreased , and there were low levels of mitotic activity in endometrial gl and s and stroma . Unusual thick-walled muscular arterioles and prominent aggregations of thin-walled vessels were present in endometrial stroma , but not in myometrium or non-endometrial vascular beds . Mitotic activity was decreased in leiomyomata . CONCLUSIONS Asoprisnil induces unique morphological changes and is associated with low levels of gl and ular and stromal proliferation in endometrium , and in leiomyomata . These changes are likely to contribute to the amenorrhoea experienced after exposure to the medication INTRODUCTION Asoprisnil , a novel orally active selective progesterone receptor modulator , is being studied for the management of symptomatic uterine leiomyomata . The exact mechanism of action is not yet discerned . The primary objectives of this double-blind , r and omized , placebo-controlled study included evaluation of the effect of asoprisnil on uterine artery blood flow . Furthermore , we assessed effects of asoprisnil on leiomyoma symptoms . PATIENTS AND METHODS Thirty-three premenopausal patients scheduled for hysterectomy due to symptomatic uterine leiomyomata were recruited in four centers and treated with 10 or 25 mg asoprisnil or placebo for 12 wk before surgery . At baseline and before hysterectomy , all patients underwent sonographic assessment to measure impedance to uterine artery blood flow , determined by resistance index and pulsatility index , as well as volumes of largest leiomyoma and uterus . In addition , patients recorded intensity and frequency of menstrual bleeding on a menstrual pictogram . Each asoprisnil treatment was compared with placebo . RESULTS The increased pulsatility index in both asoprisnil groups and the statistically significantly increased resistance index within the 25-mg asoprisnil group suggest a moderately decreased uterine artery blood flow . Analysis of menstrual pictogram scores showed a statistically significant larger decrease in frequency and intensity of bleeding for both asoprisnil groups compared with placebo . Bleeding was suppressed by asoprisnil 25 mg in 91 % of patients . Asoprisnil treatment was well tolerated when administered daily for a 12-wk period , and no serious adverse events occurred . CONCLUSION Asoprisnil moderately reduced uterine artery blood flow . This effect may contribute in part to the clinical effects of asoprisnil STUDY OBJECTIVES The primary aim was to assess long-term effects of low-dose mifepristone on myoma regression , symptoms , and endometrial pathology . The secondary aim was to assess regrowth of myomas after cessation of mifepristone . DESIGN Prospect i ve , open-label , r and omized , controlled trial of 5 mg versus 10 mg mifepristone daily for 1 year , in women with large , symptomatic myomas , with variable follow-up among a subset of subjects ( Canadian Task Force classification II-2 ) . SETTING University research group set in a community hospital . PATIENTS Forty premenopausal women with large , symptomatic myomas . INTERVENTION Oral mifepristone 5 or 10 mg daily for 1 year . MEASUREMENTS AND MAIN RESULTS Mean uterine volumes decreased in both groups by 48 % after 6 months of mifepristone and by 52 % to 53 % in both groups after 12 months . Amenorrhea occurred in 61 % to 65 % at 6 months , and 40 % to 70 % at 12 months . Eighty endometrial biopsies were performed . Simple hyperplasia was seen in 5 ( 13.9 % ) of 36 subjects at 6 months and 1 ( 4.8 % ) of 21 at 12 months . All cases of hyperplasia occurred in the 10 mg group . No endometrial sample showed cytologic atypia . Nine women were followed posttreatment for an average of 5.7 months . Uterine volumes increased among most of these subjects , although they remained on average 42 % less than baseline . CONCLUSIONS Long-term administration of low-dose mifepristone results in myoma shrinkage and amelioration of symptoms ; modest rates of low- grade endometrial hyperplasia , but no evidence of premalignant potential , also occur . Regrowth occurs slowly following cessation of the drug Uterine NK cells ( uNK ) play a role in the regulation of placentation , but their functions in nonpregnant endometrium are not understood . We have previously reported suppression of endometrial bleeding and alteration of spiral artery morphology in women exposed to asoprisnil , a progesterone receptor modulator . We now compare global endometrial gene expression in asoprisnil-treated versus control women , and we demonstrate a statistically significant reduction of genes in the IL-15 pathway , known to play a key role in uNK development and function . Suppression of IL-15 by asoprisnil was also observed at mRNA level ( p < 0.05 ) , and immunostaining for NK cell marker CD56 revealed a striking reduction of uNK in asoprisnil-treated endometrium ( p < 0.001 ) . IL-15 levels in normal endometrium are progesterone-responsive . Progesterone receptor ( PR ) positive stromal cells transcribe both IL-15 and IL-15RA . Thus , the response of stromal cells to progesterone will be to increase IL-15 trans-presentation to uNK , supporting their expansion and differentiation . In asoprisnil-treated endometrium , there is a marked downregulation of stromal PR expression and virtual absence of uNK . These novel findings indicate that the IL-15 pathway provides a missing link in the complex interplay among endometrial stromal cells , uNK , and spiral arteries affecting physiologic and pathologic endometrial bleeding OBJECTIVE To determine efficacy and safety of asoprisnil in patients with leiomyomata . DESIGN Phase 2 , multicenter , prospect i ve , r and omized , double-blind , placebo-controlled , parallel-group study . SETTING Twenty-eight sites in the United States and 1 in Canada . PATIENT(S ) One hundred twenty-nine women with leiomyomata . INTERVENTION(S ) Asoprisnil ( 5 , 10 , or 25 mg ) or placebo orally daily for 12 weeks . MAIN OUTCOME MEASURE(S ) Uterine bleeding changes by using daily bleeding diaries , hemoglobin concentrations , dominant leiomyoma and uterus volume measured sonographically , patient-reported symptoms related to bloating and pelvic pressure , endometrial thickness and morphology , hormonal parameters , and st and ard safety measures . RESULT ( S ) Asoprisnil suppressed uterine bleeding in 28 % , 64 % , and 83 % of subjects at 5 , 10 , and 25 mg , respectively , and reduced leiomyoma and uterine volumes . Median percentage decrease from baseline in leiomyoma volume was statistically significant at 25 mg compared with placebo after 4 and 8 weeks of treatment ; by week 12 , leiomyoma volume was reduced by 36 % . There was a significant reduction in bloating with the two highest doses and in pelvic pressure with 25 mg by week 12 . Asoprisnil was associated with follicular-phase estrogen concentration and minimal hypoestrogenic symptoms . CONCLUSION ( S ) After 12-week treatment , asoprisnil controlled uterine bleeding while reducing leiomyoma volume and the associated pressure symptoms . Asoprisnil was well tolerated OBJECTIVE : To assess the effect of low-dose mifepristone on quality of life , pain , bleeding , and uterine size among women with symptomatic leiomyomata . METHODS : Forty-two women with symptomatic uterine leiomyomata and uterine volume of 160 mL or more were r and omized to mifepristone , 5 mg daily , or placebo for 26 weeks . Quality of life ( Uterine Fibroid Symptoms Quality of Life Question naire and Medical Outcomes Study 36-Item Short Form survey ) and uterine and leiomyoma size ( ultrasonography ) were assessed at baseline , and at 1 month , 3 months , and 6 months of treatment . Bleeding ( daily logs and pictorial charts ) and pain ( McGill Pain Question naire ) were assessed monthly . Endometrial pathology was assessed at baseline and 6 months . RESULTS : Forty-two women were r and omized ; 37 women completed all 6 months . Women r and omized to mifepristone showed an improvement in leiomyoma-specific quality of life . Forty-one percent became amenorrheic , rates of anemia improved , and adjusted uterine size was reduced by 47 % . Compared with the placebo group , improvements in these outcomes in the treatment group were significantly greater ( P<.05 to .001 ) . There were no significant differences in adverse effects between the groups . No endometrial hyperplasia was noted in any participant . CONCLUSION : Low-dose mifepristone improves leiomyoma-specific quality of life and reduces leiomyoma size among women with symptomatic leio-myomata . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov www . clinical trials.gov NCT00133705 LEVEL OF EVIDENCE : OBJECTIVE To create and vali date a question naire for assessing symptom severity and symptom impact on health‐related quality of life for women with leiomyomata . METHODS The question naire was derived from focus groups of women with leiomyomata . Content validity was established through cognitive debriefings of women with leiomyomata and review by expert clinicians . Patients for the validation study were recruited from five gynecologists ' offices , an interventional radiology department , and a University campus . Instruments used for validation were the Short Form‐36 , Menorrhagia Question naire , the Revicki‐Wu Sexual Function Scale , and a physician and a patient assessment of severity . Item and exploratory factor analysis were performed to assess the subscale structure of the question naire . Psychometric evaluation was conducted to assess reliability and validity . Test‐retest was performed on a r and om subset of the sample within 2 weeks of the initial visit . RESULTS A total of 110 patients with confirmed leiomyomata and 29 normal subjects participated in the validation . The final question naire consists of eight symptom questions and 29 health‐related quality of life questions with six subscales . Subscale Cronbach 's α ranged from 0.83 to 0.95 , with the overall health‐related quality of life score α = 0.97 . The Uterine Fibroid Symptom and Quality of Life ( UFS‐QOL ) question naire subscales discriminated not only from normal controls but also among leiomyomata patients with varying degrees of symptom severity . Test‐retest reliability was good with intraclass correlation coefficients of 0.76–0.93 . CONCLUSION The UFS‐QOL appears to be a useful new tool for detecting differences in symptom severity and health‐related quality of life among patients with uterine leiomyomata . Additional study is underway to determine the responsiveness of the UFS‐QOL to therapies for leiomyomata OBJECTIVE To study differences in treatment effect between black and white premenopausal women prescribed ulipristal acetate ( UPA ) for symptomatic uterine fibroids . DESIGN Prospect i ve observational cohort study . SETTING Gynecology clinics . PATIENT(S ) Premenopausal women aged 18 - 55 years , at least one symptomatic uterine fibroid , UPA-naïve , and no contraindications for UPA treatment . INTERVENTION(S ) One 3-month course of UPA at 5 mg daily . MAIN OUTCOME MEASURE(S ) Patients ' ethnicity self- identification adapted from Statistics Canada National Household Survey . Change in fibroid symptoms according to Uterine Fibroid Symptoms Quality of Life Question naire symptom severity and health-related quality of life score . Bleeding symptoms and amenorrhea rates according to Aberdeen Bleeding Score . RESULT ( S ) A total of 148 patients enrolled ( 45 black , 59 white , 44 other ethnicity ) . Black patients were younger ( 40.3 y vs. 44.5 y ) with larger uteri ( 523 mL vs. 351 mL ) than white counterparts . Baseline symptom severity was similar between groups . After 3 months of UPA treatment , both groups experienced similar improvements in symptom severity . White women had 52 % greater improvement in bleeding score ( -40.3 vs. -26.5 ) and were more likely to be amenorrheic at the end of treatment ( 66 % vs. 41 % ) . Both groups experienced adverse events at similar frequencies . Black women were more dissatisfied with UPA compared with white women ( 27.3 % vs. 8 % ) . CONCLUSION ( S ) Black women had greater fibroid burden at baseline . Both ethnicities had similar improvement in fibroid symptomatology following UPA treatment , but white women experienced higher amenorrhea rates . Black women were more dissatisfied with UPA treatment , which may be related to the lower amenorrhea rates OBJECTIVE To compare the effect of 5 and 10 mg of mifepristone on uterine leiomyoma size and symptoms , and to measure side effects . METHODS Forty premenopausal women with large , symptomatic leiomyomata were r and omized to receive either 5 or 10 mg of mifepristone daily for 6 months in an open-label study . Uterine volume was measured at bimonthly intervals by sonography . Serum concentrations of hemoglobin levels , follicle-stimulating hormone , and liver enzymes were obtained , and endometrial sample s , symptoms , and menstrual bleeding were also assessed . RESULTS Nineteen of 20 subjects taking 5 mg and all 20 subjects taking 10 mg completed all 6 months of the study . Mean uterine volume shrank by 48 % ( P < .001 ) in the 5-mg group and 49 % ( P < .001 ) in the 10-mg group , a nonsignificant difference . Leiomyoma-related symptoms were comparably reduced in both groups . Amenorrhea occurred in 60–65 % of both groups . Hemoglobin levels increased by 2.5 g/dL in anemic subjects . The incidence of hot flashes increased significantly over baseline in the 10-mg group but not in the 5-mg group . Simple endometrial hyperplasia occurred in 28 % of all subjects , with no difference between groups . No atypical hyperplasia was noted . CONCLUSION Mifepristone in doses of 5 mg or 10 mg results in comparable leiomyoma regression , improvement in symptoms , and few side effects . Further study is needed to assess the long-term safety and efficacy of low-dose mifepristone BACKGROUND The efficacy and safety of oral ulipristal acetate for the treatment of symptomatic uterine fibroids before surgery are uncertain . METHODS We r and omly assigned women with symptomatic fibroids , excessive uterine bleeding ( a score of > 100 on the pictorial blood-loss assessment chart [ PBAC , an objective assessment of blood loss , in which monthly scores range from 0 to > 500 , with higher numbers indicating more bleeding ] ) and anemia ( hemoglobin level of ≤10.2 g per deciliter ) to receive treatment for up to 13 weeks with oral ulipristal acetate at a dose of 5 mg per day ( 96 women ) or 10 mg per day ( 98 women ) or to receive placebo ( 48 women ) . All patients received iron supplementation . The co primary efficacy end points were control of uterine bleeding ( PBAC score of < 75 ) and reduction of fibroid volume at week 13 , after which patients could undergo surgery . RESULTS At 13 weeks , uterine bleeding was controlled in 91 % of the women receiving 5 mg of ulipristal acetate , 92 % of those receiving 10 mg of ulipristal acetate , and 19 % of those receiving placebo ( P<0.001 for the comparison of each dose of ulipristal acetate with placebo ) . The rates of amenorrhea were 73 % , 82 % , and 6 % , respectively , with amenorrhea occurring within 10 days in the majority of patients receiving ulipristal acetate . The median changes in total fibroid volume were -21 % , -12 % , and + 3 % ( P=0.002 for the comparison of 5 mg of ulipristal acetate with placebo , and P=0.006 for the comparison of 10 mg of ulipristal acetate with placebo ) . Ulipristal acetate induced benign histologic endometrial changes that had resolved by 6 months after the end of therapy . Serious adverse events occurred in one patient during treatment with 10 mg of ulipristal acetate ( uterine hemorrhage ) and in one patient during receipt of placebo ( fibroid protruding through the cervix ) . Headache and breast tenderness were the most common adverse events associated with ulipristal acetate but did not occur significantly more frequently than with placebo . CONCLUSIONS Treatment with ulipristal acetate for 13 weeks effectively controlled excessive bleeding due to uterine fibroids and reduced the size of the fibroids . ( Funded by PregLem ; Clinical Trials.gov number , NCT00755755 . ) Selective progesterone receptor modulators ( SPRMs ) have beneficial effects in reducing the size of uterine fibroids and the amount of bleeding , but their endometrial effects have not been seen with other agents . This report describes the morphology of the endometrium after 3 mo of treatment with the SPRM , ulipristal acetate ( UPA ) . In 2 Phase III r and omized double-blind controlled clinical trials , 546 patients with uterine myomas were treated with 5 or 10 mg of UPA daily for 13 wk or placebo or gonadotropin-releasing hormone agonist . Endometrial biopsies were taken at screening , end of treatment ( 13 wk ) , and after treatment-free follow-up ( 38 wk ) . Biopsies were assessed independently by 3 pathologists according to a preset morphologic scheme . After 13 wk , the UPA-treated endometrium showed altered architectural gl and ular features including extensive cystic dilatation . The gl and ular epithelium appeared inactive or contained abortive subnuclear vacuolization , occasional mitoses , and apoptosis . Abnormal stromal vessels were commonly seen . There was a high level of agreement between pathologists on the presence or the absence of nonphysiological changes . One case of hyperplasia without atypia and 4 polyps were seen at 13 wk of UPA treatment . Six months after treatment , the endometrium returned to normal histology in the majority of the patients , with 1 polyp and no cases of hyperplasia in the UPA-treated groups , and 2 hyperplasias ( 1 with and 1 without atypia ) in the placebo or the gonadotropin-releasing hormone-agonist groups . Mild reversible thickening of the endometrium occurs in a minority of cases . It is important that pathologists are aware of the spectrum of changes induced by SPRMs to avoid misdiagnoses of endometrial hyperplasia or polyps OBJECTIVES To evaluate the efficacy and safety of 5 and 10 mg doses of mifepristone for 6 months for the treatment of uterine fibroids and to check those results at 1 year post-treatment . STUDY DESIGN R and omised double-blind clinical study carried out at the " Eusebio Hernández " Hospital , Havana , Cuba . One hundred and seventy-six women with symptomatic uterine fibroids received one daily capsule of 10 mg mifepristone orally or one daily capsule of 5 mg mifepristone orally , over 6 months . Up to two endometrial biopsies were performed . Reduction in fibroid volume was used to evaluate efficacy . RESULTS The 5 and 10 mg dose had a similar efficacy in reducing the fibroid volume , 48.1 % and 39.1 % , p=0.07 , and that of the uterus , 30.3 % and 27.2 % , p=0.63 , respectively . Twelve months after treatment the majority of the subjects were asymptomatic with symptom prevalence similar to that at the end of treatment , except for hypermenorrhea and metrorrhagia , although the intensity of hypermenorrhea was much less , p<0.01 . CONCLUSIONS ( 1 ) Both doses obtain similar results in reducing fibroid size . ( 2 ) Administering 6 months ' treatment achieves symptomatic improvement lasting 1 year in a high percentage of cases . ( 3 ) More studies need to be carried out with longer treatment and follow-up periods |
13,891 | 20,819,086 | Meta-regression indicated robustness of these findings .
Proactive anti-inflammatory therapy was generally well tolerated .
Vehicle-controlled trials indicate efficacy of proactive treatment with tacrolimus , fluticasone propionate and methylprednisolone aceponate to prevent AE flares .
Indirect evidence from vehicle-controlled trials suggests that twice weekly application of the potent topical corticosteroid fluticasone propionate may be more efficacious to prevent AE flares than tacrolimus ointment . | BACKGROUND Long-term low-level topical anti-inflammatory therapy has been suggested as a new paradigm in the treatment of atopic eczema ( AE ) .
OBJECTIVES To determine the efficacy and tolerability of topical corticosteroids and calcineurin inhibitors for flare prevention in AE . | Abstract Objective To explore the efficacy and safety of fluticasone propionate , cream and ointment , applied twice weekly in addition to maintenance treatment with emollients , in reducing the risk of relapse of chronic recurrent atopic dermatitis . Design R and omised , double blind , parallel group study of 20 weeks ' duration . Setting Dermatology outpatient clinics ( 6 countries , 39 centres ) . Participants Adult ( aged 12 - 65 ) patients with moderate to severe atopic dermatitis who were experiencing a flare . Methods Participants applied fluticasone propionate ( 0.05 % cream or 0.005 % ointment ; once or twice daily ) regularly for four weeks to stabilise their condition . The patients whose disease was brought under control then continued into a 16 week maintenance phase , applying emollient on a daily basis with a bath oil as needed and either the same formulation of fluticasone propionate or its placebo base ( emollient alone ) twice weekly to the areas that were usually affected . Main outcome measure Time to relapse of atopic dermatitis during maintenance phase . Results 376 patients entered the stabilisation phase , and 295 continued into the maintenance phase . After 16 weeks in the maintenance phase , the disease remained under control in 133 patients ( 87 using fluticasone propionate twice weekly , 46 using emollient alone ) , 135 ( 40 fluticasone propionate , 95 emollient ) had experienced a relapse , and 27 had discontinued . Median time to relapse was six weeks for emollient alone compared with more than 16 weeks for additional fluticasone propionate . Patients who applied fluticasone propionate cream twice weekly were 5.8 times less likely ( 95 % confidence interval 3.1 to 10.8 , P < 0.001 ) and patients using fluticasone propionate ointment 1.9 times less likely ( 1.2 to 3.2 , P=0.010 ) to have a relapse than patients applying emollient alone . The groups showed no differences in adverse events . Conclusion After atopic dermatitis had been stabilised the addition of fluticasone propionate twice weekly to maintenance treatment with emollients significantly reduced the risk of relapse BACKGROUND Intermittent dosing of a topical calcineurin inhibitor for preventing atopic dermatitis ( AD ) disease relapse in patients with stabilized AD has not been evaluated . OBJECTIVE We sought to evaluate the long-term efficacy and safety of 3-times-weekly use of tacrolimus ointment in preventing AD disease relapse . METHODS Adult and pediatric patients with moderate to severe AD who were clear of disease after up to 16 weeks of treatment with tacrolimus ointment were r and omized in a double-blind fashion to 3-times-weekly treatment with either tacrolimus ointment ( 0.03 % or 0.1 % ) or vehicle for 40 weeks . The primary end point was the number of flare-free treatment days . RESULTS A total of 125 patients were r and omized to tacrolimus and 72 patients to vehicle . The mean number of flare-free treatment days was 177 for tacrolimus and 134 for vehicle ( P = .003 ) . Median time to first relapse was 169 days for tacrolimus and 43 for vehicle ( P = .037 ) . LIMITATIONS Generalizability to all patients seen in clinic may be limited because only patients who responded to tacrolimus ointment in the stabilization phase were r and omized into the maintenance phase of the trial . CONCLUSIONS Maintenance therapy with tacrolimus ointment was associated with significantly more flare-free days compared with vehicle , and a significantly longer time until first disease relapse Background Rational health care decision‐making based on outcomes and economic evidence is essential to provide the best possible care for individual patients with atopic dermatitis ( AD ) Abstract Objective : To determine whether a three day burst of a potent corticosteroid is more effective than a mild preparation used for seven days in children with mild or moderate atopic eczema . Design : R and omised , double blind , parallel group study of 18 weeks ' duration . Setting : 13 general practice s and a teaching hospital in the Nottingham area . Participants : 174 children with mild or moderate atopic eczema recruited from general practice s and 33 from a hospital outpatient clinic . Interventions : 0.1 % betamethasone valerate applied for three days followed by the base ointment for four days versus 1 % hydrocortisone applied for seven days . Main outcome measures : Primary outcomes were total number of scratch-free days and number of relapses . Secondary outcomes were median duration of relapses , number of undisturbed nights , disease severity ( six area , six sign atopic dermatitis severity scale ) , scores on two quality of life measures ( children 's life quality index and dermatitis family impact question naire ) , and number of patients in whom treatment failed in each arm . Results : No differences were found between the two groups . This was consistent for all outcomes . The median number of scratch-free days was 118.0 for the mild group and 117.5 for the potent group ( difference 0.5 , 95 % confidence interval −2.0 to 4.0 , P=0.53 ) . The median number of relapses for both groups was 1.0 . Both groups showed clinical ly important improvements in disease severity and quality of life compared with baseline . Conclusion : A short burst of a potent topical corticosteroid is just as effective as prolonged use of a milder preparation for controlling mild or moderate atopic eczema in children . What is already known on this topic Topical corticosteroids have been used to control atopic eczema for 40 years No studies have compared short bursts of a potent preparation with prolonged use of a weak preparation for controlling mild or moderate disease What this study adds A short burst of a potent topical steroid is as effective and safe as prolonged use of a weak preparation for mild or moderate atopic eczema The type of preparation is i m material provided that the dosage is In this study several schedules of discontinuous application ( DA ) were tested , using various weak and strong topical corticosteroids ( CS ) . The purpose of this study was to measure the influence of corticosteroids on skin thickness by means of a mechanical method . In a first experiment , betamethasone 17,21-dipropionate ( Bet ) and fluprednidene 21-acetate ( Flu ) were applied to the skin of the volar side of the forearm at a rhythm of 1:1 ( 1 day CS , 1-day interval ) and 1:2 under occlusive dressing . The investigation period was 8 weeks . For comparison , Bet and Flu were applied continuously ( CA ) for 3 weeks . Flu thinned the skin to a lesser extent than Bet . With DA the skin was thinned to the same extent as with CA . In a second experiment , hydrocortisone 17-butyrate , betamethasone 17-valerate , desoxymethasone and hydrocortisone were tested . Here the treatment regimen was 5:9 . The CS preparations were tested for 3 months on the volar side of the forearms under occlusive dressing . Skin thinning occurred during the 5 days of CS action and , in the beginning , receded again in the CS-free interval . However , this regressive process became weaker each time . At the end of the experiment the skin thinning persisted . With the exception of hydrocortisone , all CS tested produced statistically significant skin thinning after DA . The results of the investigation presented here show that thinning of the skin must also be expected with discontinuous application of topical CS Different scoring systems have been developed to determine the severity of atopic dermatitis . The SCORAD ( SCORing Atopic Dermatitis ) , one of the best vali date d systems , is suited for clinical trials , but is too complicated and time consuming for routine clinical use . The TIS score ( Three Item Severity score ) , a simplified system , is based on the evaluation of erythema , oedema/papulation and excoriation on a scale from 0 to 3 . In order to determine the value of the TIS score we conducted a prospect i ve study in 126 children with mild to severe atopic dermatitis . Both the TIS score and the SCORAD were assessed by trained investigators . Interobserver agreement was investigated in 20 children by comparing the independently performed scores of three investigators . A positive correlation was found between the TIS score and the SCORAD ( Rank Spearman r(s)=0.86 ; p<0.0005 ) . The item which correlated best with the SCORAD was excoriation ( r(s)=0.72 ; p<0.0005 ) followed by oedema/papulations ( r(s)=0.66 ; p<0.0005 ) . Interobserver agreement which was calculated by Cohen 's kappa ( kappa ) was " excellent " for SCORAD ( kappa=0.82 ; p<0.001 ) and " fair " for TIS score ( kappa=0.58 ; p<0.01 ) . We conclude that the TIS score is a rough , though reliable and simple system for scoring atopic dermatitis . It is particularly suitable in general practice , for routine clinical use and for screening purpose s in clinical trials . For research purpose s , the objective SCORAD offers a more detailed and comprehensive assessment This study was design ed to investigate a long‐term therapeutic strategy for the management of recurring atopic dermatitis ( AD ) in adults using fluticasone propionate ( FP ) ointment ( CutivateTM ) whereby FP could help to prevent a relapse of AD once symptoms were under control . Adult patients with chronic , moderate to severe AD entered this multicentre study . All patients were initially treated with FP 0.005 % ( g/g ) ointment in two different regimens . Patients whose AD had been completely healed by these treatments then entered a long‐term treatment phase applying FP or placebo ointment once daily , two times per week for 16 weeks to ‘ known ’ healed lesions . By the end of the initial treatment period , mean SCORAD values had significantly ( P < 0.0005 ) improved from baseline . Patients who entered the maintenance phase and were treated with intermittent FP for up to 16 weeks , demonstrated its superior efficacy ( P = 0.018 ) over placebo , maintaining the improvements achieved after the initial treatment phase , reducing risk of relapse and delaying time to relapse ( P = 0.013 ) . No significant changes were detected in either treatment group in serum cortisol levels or in skin thickness measurements . Intermittent FP applied two times per week maintained a significant level of control , and delayed relapse of AD by comparison with placebo Background : Long‐term treatment for atopic dermatitis ( AD ) using low dose , intermittent , topical anti‐inflammatory agents may control acute disease and prevent relapses . This 12‐month , European , multicentre , r and omized study investigated whether the proactive use of 0.1 % tacrolimus ointment applied twice weekly can keep AD in remission and reduce the incidence of disease exacerbations ( DE ) Question : How effective and safe is the addition of twiceweekly fluticasone propionate cream or ointment to regular emollient therapy for reducing relapses in people with chronic relapsing atopic dermatitis ( AD ) ? Design : R and omized , double-blind , parallel-group study . Setting : Thirty-nine dermatology outpatient clinics in 6 European countries . Participants : PeoplewithAD , asdefinedbytheUKWorkingParty ’s refinementofHanifin and Rajka’sdiagnostic criteria , aged 12 to 65 years with moderate to severe disease who were experiencing a flare at study recruitment . Interventions : For the first 4-week phase of the study , all participants weregiven0.05%fluticasonepropionatecream or 0.005 % fluticasone propionate ointment to apply once or twice daily to stabilize their disease . Patients whose disease was brought under control were then entered into a 16-weekmaintenancephaseduringwhich timeemollients and bathoilswereusedasneeded . During themaintenance phase , patients werer and omizedto1of4groups : (1)0.05 % fluticasone propionate cream , ( 2 ) vehicle control for the cream , ( 3 ) 0.005 % fluticasone propionate ointment , or ( 4 ) vehicle control ointment . Each group was instructed toapplythecream/ointmenton2consecutivedayseachweek to areas usually affected by AD plus any new affected areas . Main Outcome Measures : Median time to relapse of AD during the 16-week maintenance phase . Severity was measured using a 3-item severity ( TIS ) score that sums the score on a scale of 0 ( absent ) to 3 ( severe ) for the 3 signs of erythema , edema/papulation , and excoriation at any site displaying a flare during the maintenance phase . A relapse was defined as a score of 4 or more and a remission as a score of 1 or less . Results : A total of 376 patients entered the initial 4-week stabilization phase during which time no significant differences in efficacy were shown between twice and once-daily application of topical fluticasone in cream or ointment form . There were 295 patients who continued into the maintenance phase ( 33 patients discontinued during the stabilization phase and 48 did not meet eligibility criteria for the maintenance phase ) . Median time to relapse was 6 weeks for emollients alone compared with more than 16 weeks for additional twiceweekly fluticasone ( P .001 for cream and P=.010 for ointment ) . After 16 weeks in the maintenance phase , the disease relapsed in 19 % ( 13/70 ) of patients using fluticasone cream and emollients compared with 64 % ( 54/84 ) of those using vehicle control plus emollients , corresponding to a rate difference of 46 % ( 95 % confidence interval , 32%-59 % ) . This difference represents a number needed to treat of 2.2 ( number of patients needed to be treated with fluticasone propionate cream to prevent 1 relapse that would have occurred with vehicle ) . For fluticasone propionate ointment , 40 % of patients ( 27/68 ) experienced relapse within 16 weeks compared with 56 % using vehicle ( 41/73 ) , corresponding to a rate difference of 16 ( 95 % confidence interval , 0.2 - 33 ) , and number needed to treat of 6.1 . One of the 376 patients developed visual signs of skin thinning related to study treatment during the stabilization phase . Conclusions : After stabilization of AD with 4 weeks of a potent topical steroid , the addition of twice-weekly fluticasone propionate to continued use of emollients significantly reduced the risk of relapse Background One of the most troublesome features of atopic dermatitis ( AD ) is its chronic relapsing nature , and there is a lack of published evidence on the best treatment strategy for long‐term management of the disease Treatment of atopic dermatitis ( AD ) in children tends to stabilize the condition in the short term . ' Maintenance ' treatment options in children are limited . To assess the efficacy and safety of twice daily treatment with fluticasone propionate 0.005 % ( FP ) ointment during 4 wk and the efficacy and safety of twice weekly maintenance treatment with FP in preventing exacerbations or remissions of AD during a 16 wk follow-up period . Ninety children ( aged 4 - 10 yr ) with moderate to severe AD were included in a r and omized , multi-centre study and received FP ointment twice daily during the acute phase . Children whose AD was in remission after 4 wk of treatment , entered the maintenance phase . In addition to twice daily emollient , children were r and omly allocated to receive FP or placebo ointment twice weekly on consecutive days . Efficacy was assessed by the objective SCORAD . Eighty-seven ( 97 % ) completed the 4-wk acute study period . Extensive remission was achieved in 78 ( 87 % ) children , and 75 children entered the maintenance phase . Intermittent treatment with FP result ed in less severe AD and significantly reduced risk of further relapse as compared with placebo . The risk of an exacerbation of AD was more than twice as high in the placebo group as in the FP group ( hazard ratio 2.182 , 95 % CI ) . AD in girls was better controlled than in boys . This long-term study shows that the addition of twice weekly FP to st and ard maintenance therapy significantly reduces the risk of relapse in children with moderate severe AD BACKGROUND Cross-sectional studies suggest an association between eczema and mental health problems , but the temporal relationship is unclear . OBJECTIVE To assess the association between infant-onset eczema and mental health problems in a prospect i ve study . METHODS Between 1995 and 1998 , a birth cohort study was recruited and followed until age 10 years . Physician-diagnosed eczema , comorbidities , and a broad set of environmental exposures were assessed at age 1 , 2 , 3 , 4 , 6 , and 10 years . First , we investigated the association between infant-onset eczema ( age 1 - 2 years ) and mental health problems at age 10 years according to the Strengths and Difficulties Question naire . Second , we analyzed the likelihood of mental health problems at age 10 years in relation to the course of eczema . RESULTS A total of 2916 infants were eligible for analysis . Compared with participants never diagnosed as having eczema , children with infant-onset eczema had a significantly increased risk for possible/probable mental health problems ( Strengths and Difficulties Question naire total score ) at age 10 years ( odds ratio , 1.49 ; 95 % CI , 1.13 - 1.96 ) and for emotional symptoms ( odds ratio , 1.62 ; 95 % CI , 1.25 - 2.09 ) . Eczema limited to infancy predicted a significantly higher risk for conduct problems at age 10 years . The strength of the association between eczema and emotional problems at age 10 years increased with increasing eczema persistence . CONCLUSION Infants with eczema are at increased risk for mental health problems at age 10 years . Even if cleared afterward , eczema at age 1 to 2 years may cause persistent emotional and behavioral difficulties |
13,892 | 26,561,917 | Current data do not demonstrate a significant difference between the ProCore and st and ard FNA needles for sample adequacy , diagnostic accuracy or acquisition of a core specimen .
However , the ProCore needle establishes the diagnosis with fewer passes | BACKGROUND AND STUDY AIMS To overcome the limitations associated with cytology , a uniquely design ed needle ( ProCore ) was introduced in an effort to obtain a core of tissue under endoscopic ultrasound ( EUS ) guidance .
However , studies comparing the sample quality between ProCore and st and ard- design fine-needle aspiration ( FNA ) needles have yielded varying results .
A systematic review and meta- analysis was therefore conducted to compare the performance of the ProCore and st and ard FNA needles when performing EUS-guided tissue acquisition . | BACKGROUND AND STUDY AIMS Histological examination of core tissue sample s may have advantages over cytology in endoscopic ultrasound (EUS)-guided sampling . We aim ed to evaluate the feasibility and efficiency of a new 22 G core biopsy needle . PATIENTS AND METHODS Consecutive patients with a pancreatic mass lesion or peri-intestinal lymphadenopathy sequentially underwent fine needle biopsy with both a newly developed 22 G core needle ( the FNB needle ) and a st and ard 22 G fine needle aspiration ( FNA ) needle , in r and omized order . RESULTS In 144 patients , mean age 48 years ( ± st and ard deviation [ SD ] 14 ; range 18 - 82 ) , with 145 lesions ( mean lesion size 39 ± 15 mm , range 15 - 99 ) , EUS-guided sampling was technically feasible with both needles in all patients . Mean number of passes to obtain sufficient tissue was 1.2 ± 0.5 with the core needle vs. 2.5 ± 0.9 with the st and ard needle ( P < 0.001 ) . FNB specimens were adequate for evaluation in 125 ( 86.2 % ) vs. 127 ( 87.6 % ) with FNA ( P = 0.72 ) . Among 139 patients available for follow-up , FNB provided a correct diagnosis in 110 ( 79.1 % ) and FNA in 112 ( 80.6 % ) ( P = 0.73 ) . Sensitivity , specificity , positive and negative predictive values , and accuracy for diagnosis of malignancy were 90 % , 100 % , 100 % , 93 % , 96 % for FNB and 77 % , 100 % , 100 % , 85 % , 92 % for FNA , respectively ( P > 0.05 ) . CONCLUSION FNB with the new 22 G core needle was technically feasible , efficient and comparable to FNA with a st and ard needle . The core needle required fewer passes to provide an adequate sample , offering potentially shorter procedure time BACKGROUND A trucut needle biopsy device that can be used to obtain specimens from the pancreas and other perigastric organs under EUS guidance has been developed and successfully tested in animals . Moreover , EUS-guided trucut needle biopsy has been used safely in humans and appears to provide more accurate results than EUS-guided FNA . This study prospect ively assessed the clinical utility of this new device in patients with solid pancreatic masses . METHODS Twenty-three consecutive patients with radiologically detected solid pancreatic masses underwent EUS-guided trucut needle biopsy . Pancreatic malignancy detected by EUS-guided trucut needle biopsy was considered a definitive diagnosis . Further diagnostic procedures and clinical course were used to establish or exclude the presence of malignancy in all other patients . RESULTS Pancreatic tissue was obtained in 17 of the 23 patients ( 74 % ) , including all patients in whom the transgastric approach was used . No acute or long-term complication was observed . Histopathologic evaluation revealed pancreatic cancer in 12 patients . CT-guided biopsy specimens were obtained in 4 of the 5 patients with a negative EUS-guided trucut needle biopsy result ; two were positive for adenocarcinoma . Overall diagnostic accuracy was 61 % . Subgroup analysis of the 16 patients in whom EUS-guided trucut needle biopsy was successful and who were available for follow-up revealed a diagnostic accuracy of 87.5 % . CONCLUSIONS This prospect i ve study demonstrates that EUS-guided trucut needle biopsy , when performed transgastrically , is safe and accurate in the evaluation of patients with solid pancreatic masses The specific needle sizes/types used in performing endoscopic ultrasound-guided fine needle aspirations ( EUS-FNA ) vary . The HD ProCore ( ™ ) is a 22-gauge beveled needle allowing for core biopsy along with aspiration material . In this study we compare this needle with a st and ard 22-gauge needle . Between April 1 , 2011 and November 15 , 2011 , 18 patients undergoing EUS-FNA using the HD ProCore ( ™ ) needle were compared to a control group of 18 cases using the st and ard 22-gauge needle . Smears were assessed for : three-dimensional clusters , thick obscuring clusters , monolayer sheets , cellularity , crowded obscuring single cells , blood , and nuclear staining . Cell blocks were assessed for cellularity and presence of diagnostic material . Records were review ed for the overall adequacy , number of FNA passes , and patient follow-up . Overall , the two needle groups demonstrated similar results for the cytology parameters , amount of diagnostic cell block material , adequacy , and accuracy . The mean number of passes to achieve adequacy varied between the groups [ 2.94 for the st and ard 22-gauge needle group versus 2.11 for the beveled needle group ( P=0.03 ) ] with no meaningful difference in case duration between needle groups . No complications were reported . The beveled EUS needle affords similar cytologic interpretability , adequacy , diagnostic accuracy , and amount of cell block material as a st and ard needle . There was a statistically significant trend toward fewer passes to achieve adequacy with the beveled EUS-FNA needle . Therefore , the EUS-FNA needle with a lateral bevel is a diagnostically similar alternative to st and ard endoscopy needles , the possibility that this beveled needle may improve per pass adequacy requires further verification Background and aims : Endoscopic ultrasound‐guided fine needle aspiration ( EUS‐FNA ) has a diagnostic accuracy of 70–90 % , depending on the site under evaluation . In order to improve EUS‐guided tissue sampling a novel 19‐gauge trucut‐type needle has been design ed to obtain core biopsies during EUS . We prospect ively evaluated the safety and accuracy of EUS‐FNA alone versus combined EUS‐FNA and trucut needle biopsy ( TNB ) in patients referred to our Unit over a 3‐year period Abstract Objective . Endoscopic ultrasonography (EUS)-guided fine-needle aspiration ( EUS-FNA ) may facilitate tissue sampling for histopathological diagnosis of subepithelial tumors ( SETs ) in the gastrointestinal ( GI ) tract . However , immunohistochemistry is not always feasible using EUS-FNA sample s due to the low quality of specimens often obtained by aspiration . This study aim ed to compare the use of 22-gauge ( G ) EUS-guided fine-needle biopsy ( EUS-FNB ) with 22 G EUS-FNA for core sampling used for histopathological examination , including immunohistochemistry , in patients with GI SETs . Methods . Twenty-eight patients with GI SETs ≥2 cm in size were prospect ively enrolled at five university hospitals in Korea between January and June 2013 . They were r and omized to undergo either EUS-FNB or EUS-FNA . Results . A total of 22 patients was finally analyzed in this study : 10 and 12 patients underwent EUS-FNA and EUS-FNB , respectively . Compared to the EUS-FNA group , the EUS-FNB group had a significantly lower median number of needle passes to obtain macroscopically optimal core sample s ( 4 vs. 2 , p = 0.025 ) ; higher yield rates of macroscopically and histologically optimal core sample s with three needle passes ( 30 % vs. 92 % , p = 0.006 ; 20 % vs. 75 % , p = 0.010 , respectively ) ; and a higher diagnostic sufficiency rate ( 20 % vs. 75 % , p = 0.010 ) . No technical difficulties were encountered in either group . Conclusions . This study shows that EUS-FNB has a better ability to obtain histological core sample s and a higher diagnostic sufficiency rate than EUS-FNA and that EUS-FNB is a feasible , safe , and preferable modality for adequate core sampling for histopathological diagnosis of GI SETs BACKGROUND AND STUDY AIMS The fanning technique for endoscopic ultrasound-guided fine-needle aspiration ( EUS - FNA ) involves sampling multiple areas within a lesion with each pass . The aim of this study was to compare the fanning and st and ard techniques for EUS - FNA of solid pancreatic masses . PATIENTS AND METHODS Consecutive patients with solid pancreatic mass lesions were r and omized to undergo EUS - FNA using either the st and ard or the fanning technique . The main outcome measure was the median number of passes required to establish diagnosis . The secondary outcome measures were the diagnostic accuracy , technical failure , and complication rate of the two techniques . RESULTS Of 54 patients , 26 were r and omized to the st and ard technique and 28 to the fanning technique . There was no difference in diagnostic accuracy ( 76.9 % vs. 96.4 % ; P = 0.05 ) , technical failure or complication rates ( none in either cohort ) . There was a significant difference in both the number of passes required to establish diagnosis ( median 1 [ interquartile range 1 - 3 ] vs. 1 [ 1 - 1 ] ; P = 0.02 ) and the percentage of patients in whom a diagnosis was achieved on pass one ( 57.7 % vs. 85.7 % ; P = 0.02 ) between the st and ard and fanning groups , respectively . CONCLUSIONS The fanning technique of FNA was superior to the st and ard approach because fewer passes were required to establish the diagnosis . If these promising data are confirmed by other investigators , consideration should be given to incorporating the fanning technique into routine practice of EUS - FNA . Registered at Clinical Trials.gov ( NCT 01501903 ) BACKGROUND AND STUDY AIMS The aim of this prospect i ve study was to compare fine-needle aspiration guided by endoscopic ultrasonography ( EUS-FNA ) using 25-gauge and 22-gauge needles with the EUS-guided 19-gauge Trucut needle biopsy ( EUS-TNB ) in patients with solid pancreatic mass . PATIENTS AND METHODS Twenty-four consecutive patients with pancreatic mass underwent biopsies by both EUS-FNA and EUS-TNB . Three needles were compared with respect to technical success rate , tissue size obtained , overall diagnostic accuracy and accuracy for histological and cytological diagnosis . RESULTS The 25-gauge EUS-FNA was technically easier and obtained superior overall diagnostic accuracy than the 22-gauge and Trucut needles , especially in lesions of the pancreas head and uncinate process . Overall accuracy for the 25-gauge , 22-gauge and Trucut needle was 91.7 % , 79.7 % and 54.1 % , respectively . Accuracy for cytological diagnosis irrespective the site of lesions with 25-gauge , 22-gauge and Trucut needles was 91.7 % , 75.0 % , and 45.8 % , respectively . For uncinate masses , it was 100 % , 33.3 % , and 0.0 % , respectively . These differences were significant . Among technically successful patients , the accuracy for histological diagnosis using the 25-gauge was significantly inferior ( P < 0.05 ) to 22-gauge and Trucut needles and the rates were 45.8 % , 78.9 % and 83.3 % . CONCLUSIONS The 25-gauge FNA needle was significantly superior in terms of technical success rate and overall diagnostic accuracy , especially for the head and uncinate lesions , compared to the 22-gauge and Trucut needles and could be considered ' the best choice needle for cytological diagnosis ' of solid pancreatic lesions . If histological diagnosis is required , the 22-gauge FNA needle and Trucut needle may be advantageous for use in head/uncinate and body/tail lesions , respectively Endoscopic ultrasound-guided fine-needle aspiration ( EUS-FNA ) is widely used for diagnosis of pancreatic lesions . The Echotip Procore Needle ( Wilson-Cook Medical ) is a new 22 G fine biopsy needle ( FNB ) for obtaining core biopsy material at time of EUS . This study aim ed to compare the technical and diagnostic performance of conventional FNA and FNB . Thirty-two patients met the design criteria for this prospect i ve paired cohort study . All lesions sample d were solid ( non-cystic ) pancreatic masses by EUS appearance . Patients were r and omized to receive FNA or FNB by first attempt . A cytopathologist performed on-site evaluations . Sample s were assessed for accuracy of diagnosis , cellularity , contamination , and sufficiency for ancillary studies . Technical and diagnostic performances were compared . Compared to FNA , there was a statistically significant decreased ability of FNB to achieve a diagnosis ( FNA 93.8 % , FNB 28.1 % , P < 0.001 ) . FNB was diagnostically superior to FNA in 1 of 32 cases . Technical failures were observed in five cases due to resistance to advancement of the FNB needle . Regarding operator perceived ease-of-use , FNA outperformed FNB ( P < 0.001 ) . Eight cases had insufficient FNB material to survive tissue processing . There was no significant difference in mean specimen cellularity between devices . FNA sample s showed an increased amount of contaminant ( P = 0.036 ) but were more sufficient for ancillary studies ( P = 0.502 ) . Although deemed comparable to FNA when providing material for cytology , the pledged advantage of FNB acting like a core biopsy needle was not apparent in our series . Additional studies are needed before routine adoption of 22 G FNB can be recommended BACKGROUND To overcome limitations of cytology , biopsy needles have been developed to procure histologic sample s during EUS . OBJECTIVE To compare 22-gauge ( G ) FNA and 22 G biopsy needles ( FNB ) for EUS-guided sampling of solid pancreatic masses . DESIGN R and omized trial . SETTING Tertiary-care medical center . PATIENTS This study involved 56 patients with solid pancreatic masses . INTERVENTION Sampling of pancreatic masses by using 22 G FNA or 22 G FNB devices . MAIN OUTCOME MEASUREMENTS Compare the median number of passes required to establish the diagnosis , diagnostic sufficiency , technical performance , complication rates , procurement of the histologic core , and quality of the histologic specimen . RESULTS A total of 28 patients were r and omized to the FNA group and 28 to the FNB group . There was no significant difference in median number of passes required to establish the diagnosis ( 1 [ interquartile range 1 - 2.5 ] vs 1 [ interquartile range 1 - 1 ] ; P = .21 ) , rates of diagnostic sufficiency ( 100 % vs 89.3 % ; P = .24 ) , technical failure ( 0 vs 3.6 % ; P = 1.0 ) , or complications ( 3.6 % for both ) between FNA and FNB needles , respectively . Patients in whom diagnosis was established in passes 1 , 2 , and 3 were 64.3 % versus 67.9 % , 10.7 % versus 17.9 % , and 25 % versus 3.6 % , respectively , for FNA and FNB cohorts . There was no significant difference in procurement of the histologic core ( 100 % vs 83.3 % ; P = .26 ) or the presence of diagnostic histologic specimens ( 66.7 % vs 80 % ; P = .66 ) between FNA and FNB cohorts , respectively . LIMITATIONS Only pancreatic masses were evaluated . CONCLUSION Diagnostic sufficiency , technical performance , and safety profiles of FNA and FNB needles are comparable . There was no significant difference in yield or quality of the histologic core between the 2 needle types BACKGROUND AND STUDY AIMS An endoscopic ultrasound (EUS)-guided fine needle biopsy ( EUS-FNB ) device using a core biopsy needle was developed to improve diagnostic accuracy by simultaneously obtaining cytological aspirates and histological core sample s. We prospect ively compared the diagnostic accuracy of EUS-FNB with st and ard EUS-guided fine needle aspiration ( EUS-FNA ) in patients with solid pancreatic masses . PATIENTS AND METHODS Between January 2012 and May 2013 , consecutive patients with solid pancreatic masses were prospect ively enrolled and r and omized to undergo EUS-FNB using a core biopsy needle or EUS-FNA using a st and ard aspiration needle at a single tertiary center . The specimen was analyzed by onsite cytology , Papanicolaou-stain cytology , and histology . The main outcome measure was diagnostic accuracy for malignancy . The secondary outcome measures were : the median number of passes required to establish a diagnosis , the proportion of patients in whom the diagnosis was established with each pass , and complication rates . RESULTS The overall accuracy of combining onsite cytology with Papanicolaou-stain cytology and histology was not significantly different for the FNB ( n = 58 ) and FNA ( n = 58 ) groups ( 98.3 % [ 95 % CI 94.9 % - 100 % ] vs. 94.8 % [ 95 % CI 91.9 % - 100 % ] ; P = 0.671 ) . Compared with FNA , FNB required a significantly lower median number of needle passes to establish a diagnosis ( 1.0 vs. 2.0 ; P < 0.001 ) . On subgroup analysis of 111 patients with malignant lesions , the proportion of patients in whom malignancy was diagnosed on the first pass was significantly greater in the FNB group ( 72.7 % vs. 37.5 % ; P < 0.001 ) . CONCLUSIONS The overall accuracy of FNB and FNA in patients with solid pancreatic masses was comparable ; however , fewer passes were required to establish the diagnosis of malignancy using FNB.This study was registered on the UMIN Clinical Trial Registry ( UMIN000014057 ) BACKGROUND AND STUDY AIMS A new core biopsy needle for endoscopic ultrasound (EUS)-guided sampling has recently been developed . The aim of this prospect i ve multicenter study was to compare this needle with a st and ard needle in patients with solid pancreatic masses . PATIENTS AND METHODS Consecutive patients with solid pancreatic masses referred to 17 centers for EUS-guided sampling were included . Each patient had two passes with a st and ard 22 G needle and a single pass with a 22 G core needle performed in a r and omized order . Sample s from both needles were separately processed for liquid-based cytology and cell-block preparation and were assessed independently by two blinded expert pathologists . The primary endpoint was the accuracy of the detection of malignancy . The reference st and ard was based on further cytohistological analysis obtained under ultrasound or computed tomography scanning , endoscopic or surgical guidance , and /or by clinical follow-up with repeated imaging examinations for at least 12 months . The secondary endpoints were the rate of technical failure and the quality of the cytohistological sample s obtained . RESULTS Of the 80 patients included ( 49 men ; mean age 67.1 ± 11.1 ) , 87.5 % had final malignant diagnoses ( adenocarcinoma n = 62 , 77.5 % ) . There was no difference between the needles in diagnostic accuracy ( st and ard needle 92.5 % vs. core needle 90 % ; P = 0.68 ) or technical failure . Both pathologists found the overall sample quality significantly better for the st and ard needle ( expert 1 , P = 0.009 ; expert 2 , P = 0.002 ) . CONCLUSIONS The diagnostic accuracy of EUS sampling for solid pancreatic masses using st and ard and core needles seems comparable but with a better overall histological sample quality for the former . Clinical Trial.gov identifier : NCT01479803 |
13,893 | 23,796,001 | Favorable results were found in all outcome categories , and meta-analyses conducted for therapeutic , safety , hospitalization , and adherence were significant ( P < .001 ) , favoring pharmacist care over comparison .
Pharmacist intervention has favorable effects on therapeutic , safety , hospitalization , and adherence outcomes in older adults . | OBJECTIVES To conduct a systematic review and meta-analyses to examine the effects of pharmacists ' care on geriatric patient-oriented health outcomes in the United States ( U.S. ) . | OBJECTIVES To study the feasibility and effectiveness of a discharge planning intervention . DESIGN Quasi-experimental pre-post study design . SETTING General medicine wards at three hospitals : an academic medical center , a community teaching hospital , and a community-based nonteaching hospital . PARTICIPANTS All patients aged 65 and older admitted to the hospitalist services . INTERVENTION The intervention toolkit had five core elements : admission form with geriatric cues , facsimile to the primary care provider , interdisciplinary worksheet to identify barriers to discharge , pharmacist-physician collaborative medication reconciliation , and predischarge planning appointments . MEASUREMENTS Thirty-day readmission and return to emergency department rates and patient satisfaction with discharge . Odds ratios were determined , and site effects were examined accordig to interaction terms and Breslow Day statistics . RESULTS Two hundred thirty-seven patients were followed during the preintervention period , and 185 were exposed to the intervention . Patients characteristics were similar across the two time periods . The proportion of patients with high- quality transitions home , measured according to Coleman 's Care Transition Measures , increased from 68 % to 89 % ( odds ratio (OR)=3.49 , 95 % confidence interval (CI)=2.06 - 5.92 ) . Return to the emergency department within 3 days of discharge was lower in the intervention period ( 10 % vs 3 % , OR=0.25 , 95 % CI=0.10 - 0.62 ) . At 30 days , there was a lower rate of readmission ( 22 % vs 14 % , OR=0.59 , 95 % CI=0.34 - 0.97 ) and fewer visits to the emergency department ( 21 % vs 14 % , OR=0.61 , 95 % CI=0.36 - 1.03 ) ( P=.06 ) . CONCLUSION When hospitalized elderly patients are treated with consideration of their specific needs , healthcare outcomes can be improved BACKGROUND Falls are the leading cause of both fatal and nonfatal injuries among older adults in the United States . Medications that affect the central nervous system are known to increase the risk of falling . OBJECTIVE The purpose of this study was to assess the effects of a community pharmacy-based falls-prevention program targeting high-risk older adults on the rates of recurrent falls , injurious falls , and filling prescriptions for medications that have been associated with an increased risk of falling . METHODS This was a r and omized controlled trial of participants recruited through a community pharmacy chain in North Carolina . The 2-year study consisted of a 1-year " look-back " period before r and omization and a 1-year follow-up period after r and omization . Patients were eligible to participate if they were ≥65 years of age , had fallen at least once during the 1-year period preceding enrollment , and were taking medications associated with an increased risk of falling . Medications classified as high risk included benzodiazepines , antidepressants , anticonvulsants , sedative hypnotics , opioid analgesics , antipsychotics , and skeletal muscle relaxants . Participants were assigned to either the intervention arm or the control arm ; participants in the intervention arm were invited to attend a face-to-face medication consultation conducted by a community pharmacy resident , whereas those in the control arm received no medication consultation . The primary end point was the rate of recurrent falls during the 1-year followup period . Secondary end points were the total number of prescriptions for high-risk medications filled during the follow-up period and either discontinued use or a reduction in the dosage of a high-risk medication during the follow-up period . RESULTS One hundred eighty-six patients ( 132 women , 54 men ; 88.7 % white ) were enrolled . Intention-to-treat ( ITT ) analyses revealed no significant differences in the rates of recurrent falls , injurious falls , or filling prescriptions for high-risk medications . However , 13 patients in the intervention group either discontinued use of a high-risk medication or had the dosage reduced during the follow-up period , compared with 5 patients in the control group ( χ(2 ) = 3.94 ; P < 0.05 ) . As-treated analyses revealed numeric reductions in the rates of falls ( rate ratio [ RR ] = 0.76 ; 95 % CI , 0.53 - 1.09 ) , injurious falls ( RR= 0.67 ; 95 % CI , 0.43 - 1.05 ) , and filling prescriptions for high-risk medications ( RR= 0.85 ; 95 % CI , 0.72 - 1.03 ) after receipt of the intervention , but the differences were not statistically significant . CONCLUSIONS Results of this study support the feasibility of using community pharmacies to deliver a falls-prevention program targeting high-risk older adults . Although the ITT analyses revealed no significant reduction in the rate of recurrent falls , injurious falls , or overall use of high-risk medications , individuals in the intervention group were more likely than those in the control group to discontinue use of a high-risk medication or have the dosage reduced during the 1-year follow-up period . More work is needed to evaluate the intervention using a larger sample size that provides greater power to detect clinical ly meaningful effects of reduction in the use of high-risk medications on preventing or reducing falls in the high-risk population The effects of a fall-focused pharmaceutical intervention program ( FFPIP ) on the clinical and economic outcomes of elderly patients who fall while residing in a rehabilitation center are described . The objectives of this retrospective observational study were to identify the differences in the number of patient falls among elderly patients before and after pharmaceutical interventions , identify the cost savings related to decreasing the number of falls , and determine whether a relationship exists between falls among the elderly and specific medication classes . A data collection tool was developed by the investigators to record demographics and medication use . Two hundred patients were r and omly selected from the preintervention ( October 1 , 1999-September 30 , 2000 ) and postintervention ( October 1 , 2000-September 30 , 2001 ) periods . Two data collectors collected data from patient medical records to test the data collection tool and ensure accuracy . The number of patient falls was reduced in the postintervention group by 47 % , result ing in a future savings of $ 7.74 per patient per day . The use of several classes of medication also decreased in the postintervention period : cardiovascular agents , 10.7 % ; analgesics , 6.3 % ; psychoactive drugs , 18.2 % ; and sedatives and hypnotics , 13.9 % . Patients most likely to fall were male , greater than 76 years of age , had a cardiovascular- or orthopedic-related diagnosis , and were taking analgesics , cardiovascular agents , and central nervous system agents , yet the intervention had a more significant effect on female patients . Implementation of an FFPIP decreased falls by 47 % and decreased the use of cardiovascular drugs , analgesics , psychoactive medications , and sedatives and hypnotics CONTEXT Poor medication adherence diminishes the health benefits of pharmacotherapies . Elderly patients with coronary risk factors frequently require treatment with multiple medications , placing them at increased risk for nonadherence . OBJECTIVE To test the efficacy of a comprehensive pharmacy care program to improve medication adherence and its associated effects on blood pressure ( BP ) and low-density lipoprotein cholesterol ( LDL-C ) . DESIGN , SETTING , AND PATIENTS A multiphase , prospect i ve study with an observational phase and a r and omized controlled trial conducted at the Walter Reed Army Medical Center of 200 community-based patients aged 65 years or older taking at least 4 chronic medications . The study was conducted from June 2004 to August 2006 . INTERVENTION After a 2-month run-in phase ( measurement of baseline adherence , BP , and LDL-C ) , patients entered a 6-month intervention phase ( st and ardized medication education , regular follow-up by pharmacists , and medications dispensed in time-specific packs ) . Following the intervention phase , patients were r and omized to continued pharmacy care vs usual care for an additional 6 months . MAIN OUTCOME MEASURES Primary end point of the observation phase was change in the proportion of pills taken vs baseline ; secondary end points were the associated changes in BP and LDL-C. Primary end point of the r and omization phase was the between-group comparison of medication persistence . RESULTS A total of 200 elderly patients ( 77.1 % men ; mean [ SD ] age , 78 [ 8.3 ] years ) , taking a mean ( SD ) of 9 ( 3 ) chronic medications were enrolled . Coronary risk factors included drug-treated hypertension in 184 patients ( 91.5 % ) and drug-treated hyperlipidemia in 162 ( 80.6 % ) . Mean ( SD ) baseline medication adherence was 61.2 % ( 13.5 % ) . After 6 months of intervention , medication adherence increased to 96.9 % ( 5.2 % ; P<.001 ) and was associated with significant improvements in systolic BP ( 133.2 [ 14.9 ] to 129.9 [ 16.0 ] mm Hg ; P = .02 ) and LDL-C ( 91.7 [ 26.1 ] to 86.8 [ 23.4 ] mg/dL ; P = .001 ) . Six months after r and omization , the persistence of medication adherence decreased to 69.1 % ( 16.4 % ) among those patients assigned to usual care , whereas it was sustained at 95.5 % ( 7.7 % ) in pharmacy care ( P<.001 ) . This was associated with significant reductions in systolic BP in the pharmacy care group ( -6.9 mm Hg ; 95 % CI , -10.7 to -3.1 mm Hg ) vs the usual care group ( -1.0 mm Hg ; 95 % CI , -5.9 to 3.9 mm Hg ; P = .04 ) , but no significant between-group differences in LDL-C levels or reductions . CONCLUSIONS A pharmacy care program led to increases in medication adherence , medication persistence , and clinical ly meaningful reductions in BP , whereas discontinuation of the program was associated with decreased medication adherence and persistence . TRIAL REGISTRATION clinical trials.gov Identifier : Clinical pharmacists , under the supervision of a family practitioner physician , assumed responsibility for drug management of geriatric patients in a Los Angeles skilled nursing facility . In a quasi-experimental , pretest-post-test control group design , outcome criteria were measured . Compared with the control group which received traditional patient care , the prescribing clinical pharmacists ' group had a significantly lower number of deaths ( P = 0.05 ) , a significantly higher number of patients being discharged to lower levels of care ( P = 0.03 ) , and a significantly lower average number of drugs per patient ( P = 0.04 ) . The lower number of patients hospitalized approached significance ( P = 0.06 ) in the prescribing clinical pharmacists ' group . The practice of having clinical pharmacists prescribe drug therapy and render general care , under the supervision of a physician , has the potential for saving the health care system approximately $ 70,000 per year per 100 skilled nursing facility beds The outcome of a department of pharmacy-initiated " streamlining " study design ed to promote cost-conscious modifications of empirically selected antibiotic therapy is described . Two hundred forty-one evaluable adult patients started on restricted-use antibiotics at this university-affiliated community private teaching hospital were enrolled in a 9-week prospect i ve streamlining study . Patients were alternately assigned to a Control ( i.e. , no pharmacist-initiated streamlining recommendations offered based on culture and susceptibility reports ) or a Pharmacist Intervention group ( i.e. , pharmacist offers recommendations to streamline therapy ) . A statistically significant greater number of patients had their empiric antibiotic treatment courses modified to more appropriate antibiotic choices after receipt of culture and susceptibility reports among private prescribers in the Pharmacist Intervention group ( 83 % ) than in the Control group ( 38 % ) ( p = .006 ) . Additionally , pharmacists were overall successful in gaining prescriber acceptance for 64 % of recommended changes of empiric antibiotic treatment courses before the receipt of culture and susceptibility reports ( e.g. , dose and /or frequency changes ) . There was no program effect observed with respect to improved physician response to microbiologic data that would allow streamlining empirical antibiotic choices in the Housestaff ( i.e. , medical or surgical residents ) , or infectious disease consultant prescriber groups . Projected overall annual cost savings that would be achieved as a result of continued efforts by pharmacists directed at streamlining empirical " restricted " antibiotic regimens is approximately + 40,000 RATIONALE Care coordination has shown inconsistent results as a mechanism to reduce hospital readmission and postdischarge emergency department ( ED ) visit rates . OBJECTIVE To assess the impact of a supplemental care bundle targeting high-risk elderly in patients implemented by hospital-based staff compared to usual care on a composite outcome of hospital readmission and /or ED visitation at 30 and 60 days following discharge . PATIENTS / METHODS R and omized controlled pilot study in 41 medical in patients predisposed to unplanned readmission or postdischarge ED visitation , conducted at Baylor University Medical Center . The intervention group care bundle consisted of medication counseling/reconciliation by a clinical pharmacist ( CP ) , condition specific education/enhanced discharge planning by a care coordinator ( CC ) , and phone follow-up . RESULTS Groups had similar baseline characteristics . Intervention group readmission/ED visit rates were reduced at 30 days compared to the control group ( 10.0 % versus 38.1 % , P = 0.04 ) , but not at 60 days ( 30.0 % versus 42.9 % , P = 0.52 ) . For those patients who had a readmission/postdischarge ED visit , the time interval to this event was longer in the intervention group compared to usual care ( 36.2 versus 15.7 days , P = 0.05 ) . Study power was insufficient to reliably compare the effects of the intervention on lengths of index hospital stay between groups . CONCLUSIONS A targeted care bundle delivered to high-risk elderly in patients decreased unplanned acute health care utilization up to 30 days following discharge . Dissipation of this effect by 60 days postdischarge defines reasonable expectations for analogous hospital-based educational interventions . Further research is needed regarding the impacts of similar care bundles in larger population s across a variety of inpatient setting STUDY OBJECTIVE To assess the impact of a pilot pharmacist-managed medication reconciliation program on mortality and use of health care services in patients discharged to home from a skilled nursing facility ( SNF ) . DESIGN Quasi-experimental , controlled trial . SETTING Health maintenance organization ( HMO ) . PATIENTS Five hundred twenty-one HMO members . INTERVENTION Patients were assigned to the medication reconciliation program ( 113 patients ) or to the usual care control group ( 408 patients ) after discharge to home from an SNF . Assignment to the medication reconciliation group or to the control group was based on provider su bmi ssion of a discharge summary within 0 - 48 hours of discharge or more than 48 hours after discharge , respectively . MEASUREMENTS AND MAIN RESULTS Integrated electronic medical and pharmacy data and multivariate analyses were used to assess the medication reconciliation program with regard to its impact on postdischarge mortality , rehospitalization , and ambulatory clinic and emergency department visits . Compared with usual care during the 60 days after discharge from the SNF , patients who received the medication reconciliation intervention had an adjusted 78 % reduction in the risk of death ( adjusted hazard ratio 0.22 , 95 % confidence interval [ CI ] 0.06 - 0.88 ) and a trend toward an increased rate of ambulatory care visits ( adjusted incidence risk ratio 1.17 , 95 % CI 0.99 - 1.37 ) . No significant differences were noted in adjusted risks of an emergency department visit and rehospitalization ( p>0.05 ) between the medication reconciliation and usual care groups . CONCLUSION Our data support the hypothesis that a formal medication reconciliation process , with its increased coordination of information between health care providers and patients , can decrease mortality after discharge from an SNF . Our findings support the role of medication reconciliation as an integral step in the transitional care process and interests of health care accrediting agencies , such as the Joint Commission , that have included medication reconciliation as an important initiative OBJECTIVE To evaluate medication adherence and treatment outcomes in elderly out patients using daily-dose blister packaging ( Pill Calendar ) compared with medications packaged in bottles of loose tablets . DESIGN R and omized controlled trial . SETTING Ambulatory care clinics at Ohio State University Medical Center , Columbus ; University of Arizona Health Science Center , Tucson ; and Riverside Method ist Hospital Family Medicine Clinic , Columbus , Ohio , from July 1 , 2002 , to December 31 , 2004 . PATIENTS 85 individuals 65 years of age or older being treated with lisinopril for hypertension . INTERVENTION Patients were r and omly assigned to receive lisinopril in either daily-dose blister packaging ( Pill Calendar ) or traditional bottles of loose tablets . MAIN OUTCOME MEASURES Adherence was assessed by prescription refill regularity and medication possession ratio ( MPR ) . Treatment outcome and use of medical services were assessed by medical record review of blood pressure and morbidity associated with poorly controlled hypertension . RESULTS Patients receiving lisinopril in the daily-dose blister packaging ( Pill Calendar ) refilled their prescriptions on time more often ( P = 0.01 ) , had higher MPRs ( P = 0.04 ) , and had lower diastolic blood pressure ( P = 0.01 ) than patients who had their medications packaged in traditional bottles of loose tablets . CONCLUSION Providing medications in a package that identifies the day each dose is intended to be taken and provides information on proper self-administration can improve treatment regimen adherence and treatment outcomes in elderly patients PURPOSE To evaluate the effect of sustained clinical pharmacist interventions involving elderly out patients with polypharmacy and their primary physicians . PATIENTS AND METHODS R and omized , controlled trial of 208 patients aged 65 years or older with polypharmacy ( > or = 5 chronic medications ) from a general medicine clinic of a Veterans Affairs Medical Center . A clinical pharmacist met with intervention group patients during all scheduled visits to evaluate their drug regimens and make recommendations to them and their physicians . Outcome measures were prescribing appropriateness , health-related quality of life , adverse drug events , medication compliance and knowledge , number of medications , patient satisfaction , and physician receptivity . RESULTS Inappropriate prescribing scores declined significantly more in the intervention group than in the control group by 3 months ( decrease 24 % versus 6 % , respectively ; P = 0.0006 ) and was sustained at 12 months ( decrease 28 % versus 5 % , respectively ; P = 0.0002 ) . There was no difference between groups at closeout in health-related quality of life ( P = 0.99 ) . Fewer intervention than control patients ( 30.2 % ) versus 40.0 % ; P = 0.19 ) experienced adverse drug events . Measures for most other outcomes remained unchanged in both groups . Physicians were receptive to the intervention and enacted changes recommended by the clinical pharmacist more frequently than they enacted changes independently for control patients ( 55.1 % versus 19.8 % ; P < 0.001 ) . CONCLUSIONS This study demonstrates that a clinical pharmacist providing pharmaceutical care for elderly primary care patients can reduce inappropriate prescribing and possibly adverse drug effects without adversely affecting health-related quality of life BACKGROUND Older adults frequently have conditions requiring oral anticoagulation . Although clearly benefiting from oral anticoagulation , they are at increased risk for bleeding complications . Regular monitoring to optimize anticoagulation and to reduce the chance of major bleeding complications is required . The impact of oral anticoagulation monitoring by pharmacists in patients older than 75 years of age has not been described well . OBJECTIVE To compare warfarin therapy prescribed and monitored by physicians to a pharmacist-monitored anticoagulation service in a cohort of older veterans . METHODS Retrospective chart review utilizing the Houston VA Medical Center 's pharmacy data base . Among all out patients aged 75 years or older filling warfarin prescriptions between 1 March 2003 to 1 March 2005 , and who were either monitored in a pharmacist 's clinic or not , 103 patients per group were r and omly selected . Information on demographics , indication for and length of warfarin therapy , INR values , and thromboembolic and bleeding events were abstract ed . Differences were analysed using chi-squared test , Fisher 's Exact test , and unpaired Student t-test . RESULTS A total of 1521 patients ( 440 in the pharmacist-monitored group , 1081 in the traditionally monitored group ) met our inclusion criteria . One hundred and three patients per group were r and omly selected for chart review . Although no significant difference in percentage of therapeutic INR values ( 48.1 % pharmacist group , 46.4 % conventional group ) or in the incidence of major bleeding events was found , thromboembolic events occurred significantly less frequently in the pharmacist-monitored group ( 2 events vs. 12 events , P = 0.01 ) . Minor bleeding events were more frequent in the pharmacist-monitored group ( 50 vs. 17 , P < 0.01 ) . However , time to follow-up after a sub- or supra-therapeutic INR was significantly shorter in the pharmacist monitored group ( 22 days vs. 68 days , and 14 days vs. 32 days , respectively ) . CONCLUSION Pharmacist-monitored anticoagulation was associated with reduced thromboembolic events , an increase in minor bleeding events , and no difference in major bleeding events . Overall such monitoring by pharmacists should be recommended for older adults PURPOSE To assess the incidence of and risk factors for adverse drug events in the long-term care setting . METHODS We performed a cohort study of all long-stay residents of two academic long-term care facilities over a period of up to 9 months during 2000 to 2001 . We assessed the number of adverse drug events , the severity of events ( classified as less serious , serious , life threatening , or fatal ) , and whether the events were preventable . A case-control study was nested within the prospect i ve study to identify resident-level risk factors for the occurrence of adverse drug events . RESULTS There were 815 adverse drug events , of which 42 % were judged preventable . The overall rate of adverse drug events was 9.8 per 100 resident-months , with a rate of 4.1 preventable adverse drug events per 100 resident-months . Errors associated with preventable events occurred most often at the stages of ordering and monitoring . Residents taking medications in several drug categories were at increased risk of a preventable adverse event . In multivariate analyses , the adjusted odds ratio was 3.4 ( 95 % confidence interval [ CI ] : 2.0 to 5.9 ) for those taking antipsychotic agents , 2.8 ( 95 % CI : 1.6 to 4.7 ) for those taking anticoagulants , 2.2 ( 95 % CI : 1.2 to 4.0 ) for those taking diuretics , and 2.0 ( 95 % CI : 1.1 to 3.7 ) for those taking antiepileptics . CONCLUSION Our findings reinforce the need for a special focus on the ordering and monitoring stages of pharmaceutical care for preventing adverse drug events in the long-term care setting . Patients taking antipsychotic agents , anticoagulants , diuretics , and antiepileptics are at increased risk This study assessed the impact of clinical pharmacists ' consultations on drug regimens , compliance , and health service use of geriatric hospitalized patients ( N = 706 ) discharged on 3 or more medications . Pharmacists consulted with experimental patients at discharge and 3 months thereafter , and with physicians as needed . Controls received usual care . At 6 - 8 weeks after enrollment , experimental patients were more knowledgeable about regimens than controls . At 12 - 14 weeks , they were on fewer medications and less complex regimens , and had better compliance scores . There was no effect on service use or charges , perhaps due to inadequate sample size and lack of targeted drug groups analysis . The authors conclude that clinical pharmacists ' consultations can improve geriatric patients ' drug regimens and compliance . Findings further suggest the need for replication among large cohorts of patients at high risk , due to the use of medications most likely to have a potential for serious outcomes and to be vulnerable to physician prescribing error |
13,894 | 15,720,937 | The evidence indicated that higher doses of methadone and buprenorphine are associated with better treatment outcomes .
Low-dose methadone ( 20 mg per day ) is less effective than buprenorphine ( 2 - 8 mg per day ) .
Higher doses of methadone ( > 50 - 65 mg per day ) are slightly more effective than buprenorphine ( 2 - 8 mg per day ) .
There was some evidence that primary care could be an effective setting to provide this treatment , but such evidence was sparse .
The literature supports the effectiveness of substitute prescribing with methadone or buprenorphine in treating opiate dependence .
Evidence is also emerging that the provision of methadone or buprenorphine by primary care physicians is feasible and may be effective | BACKGROUND Opiate dependence is a major health and social issue in many countries .
A mainstay of therapy has been methadone maintenance treatment , but other treatments , particularly buprenorphine , are increasingly being considered .
AIM To conduct a systematic review to synthesis e and critically appraise the evidence on the effectiveness of community maintenance programmes with methadone or buprenorphine in treating opiate dependence . | This study examined the reinforcing effects of hydromorphone ( HYD ) ( 0 , 4 , 8 , and 16 mg/70 kg i.m . ) in heroin-dependent outpatient volunteers maintained on buprenorphine ( BUP ) at doses of 2 , 4 , and 8 mg , each for 2 weeks . Following a week of maintenance at each dose , volunteers received injections of one of the four HYD doses under double-blind conditions . Eight volunteers ( abstainers ) were heroin-free during HYD test weeks , whereas six volunteers remained heroin-positive ( nonabstainers ) . Among abstainers , HYD had minimal reinforcing value , whereas in nonabstainers there were marked dose-related increases in HYD reinforcing value , which were not attenuated by increasing doses of BUP . A similar pattern was found for HYD subjective agonist effects . Heroin craving among nonabstainers was significantly higher compared with abstainers , and was reduced in a dose-related manner by HYD . Although BUP and HYD produced dose-related miosis , abstinence status had no differential effect . In summary , BUP effects on opioid reinforcement were consistent from outpatient setting ( heroin abstinence ) to laboratory setting ( decreased HYD reinforcement ) , supporting the validity of this laboratory model It is estimated that more than 500 000 people in the United States are dependent on opioids [ 1 , 2 ] . Methadone , a synthetic opioid first reported as a treatment agent for opioid dependence by Dole and Nysw and er in 1965 [ 3 ] , is the most widely used pharmacologic treatment for opioid dependence . The National Drug and Alcoholism Treatment Unit Survey ( NDATUS ) determined a point prevalence of 92 715 opioid abusers treated in 758 methadone treatment programs on 30 September 1989 [ 4 ] . When used in conjunction with counseling services , methadone treatment has been associated with reduced rates of criminal activity , illicit drug use , and needle sharing and with improved rates of employment [ 5 - 9 ] . With the recognition of intravenous drug use as a primary risk factor for infection with human immunodeficiency virus ( HIV ) , improved access to methadone treatment has been identified as an important means for reducing the risk of HIV infection [ 10 , 11 ] . Although methadone treatment is effective in decreasing opioid use , recent studies have reported considerable variability across clinics in rates of continued intravenous drug use during treatment [ 12 ] . One aspect of this problem is that intravenous use of cocaine has become a serious problem among methadone treatment patients [ 13 - 16 ] . Few systematic studies have addressed the efficacy of methadone treatment since the onset of the cocaine epidemic [ 17 ] . Such research could re-evaluate in a contemporary population sample methadone 's specific pharmacologic efficacy in decreasing opioid use [ 18 - 20 ] while providing new information about any potential effect of methadone treatment on concurrent cocaine use . The issue of appropriate methadone dosing levels is highly pertinent because low-dose treatment has been strongly associated with poor drug use outcomes in descriptive clinical studies [ 12 , 21 ] and because a substantial number of clinics continue to use low doses of methadone [ 22 ] . For example , a report prepared by the General Accounting Office ( GAO ) that summarized the dosing practice s of 24 methadone programs in eight states found that doses ranged widely ( from 21 to 68 mg ) and 29 % had a mean dose of less than 40 mg [ 23 ] . Thus , despite more than 25 years of clinical experience , optimal dosing levels of methadone remain controversial [ 24 , 25 ] . Previous studies of methadone dosing have either surveyed clinics for their dosing practice and related doses to clinic-wide outcomes or have r and omly assigned patients to a specific predetermined dose of methadone using clinical trial methods . Naturalistic survey studies [ 5 , 6 , 12 , 21 , 26 ] , although valuable for identifying associations between dose and outcome , are method ologically compromised by confounding factors that differ across the clinics surveyed . Previous early clinical trials of methadone dosing [ 27 - 29 ] are also method ologically compromised ( for example , being single-blinded ) or only tested higher doses of methadone [ 30 ] . Thus there is a need for well-controlled research on methadone dosing reflecting doses in common use and incorporating the changing patient population . In this controlled clinical trial we compared moderate and low methadone dosing to methadone-free treatment , providing data in a contemporary population sample of opioid addicts and examining the effect of methadone dose on cocaine as well as opioid use . Methods Participants were 247 persons who had consecutive admissions to a methadone research clinic from September 1988 through July 1990 . The mean age was 34 years , 70 % were male , and 50 % were black . Most were unmarried ( 84 % ) and unemployed ( 62 % ) . They had an average of 11 years of education , were generally legally free ( 72 % ) , and had a mean of two previous admissions for drug abuse treatment . Their primary drug of choice was intravenous heroin , and 47 % reported using cocaine in the 30 days before their application to treatment . Eligibility criteria for study participation were age between 18 and 50 years , history of intravenous opioid dependence ( including documentation of previous treatment for opioid dependence or legal involvement secondary to opioid use , a urine sample positive for opioids , and physical examination consistent with acute and chronic needle use ) , no chronic medical illnesses , absence of a major mental illness , a negative pregnancy test for women , and at least 3 months since the patient 's last treatment at the clinic . Applicants who failed to fulfill the study 's eligibility criteria were assisted in seeking an alternate treatment program . The study was approved by the institutional review board , and informed consent was obtained from each patient at the time of admission to the study . Study Procedures Applicants who fulfilled the eligibility criteria were admitted to a 6-month short-term methadone treatment program . Participants were stratified as to race and sex and were assigned to one of three fixed-dose methadone schedules ( Figure 1 ) . Treatment group assignment , stabilization doses , and dosing schedules were double-blind for all patients and the clinic staff who had patient contact . All patients received a minimum of 35 days of active methadone during the first 5 weeks of treatment ; this was followed by a 15-week stabilization period at either 50 , 20 , or 0 mg of methadone . Thus , patients assigned to the 0-mg treatment group received 35-day methadone detoxification . During weeks 21 through 26 , the methadone dose was gradually tapered for those patients still receiving active medication because this was a short-term ( 182-day ) treatment episode . A sub sample of patients ( n = 44 ) assigned to the 0-mg treatment group received a more prolonged ( 8-week ) induction period , reaching 0 mg at the start of week 9 to compare the effects of a faster to a slower detoxification protocol . In this report data for patients in the alternate 0-mg treatment groups are collapsed . Figure 1 . Dosing schedule . Treatment Procedures Patients were assigned an individual counselor who set treatment goals and developed an individualized treatment plan . Patients were given weekly group therapy focusing on relapse prevention . On-site medical services were provided by a full-time internist and a part-time nurse practitioner . Take-home medication was provided only on legal holidays and for documented extenuating circumstances ( for example , funeral out of town for a death in the family ) . Patients who failed to attend the clinic for 3 consecutive days were discharged from treatment . Outcome Measures Treatment Retention and Compliance Treatment retention was calculated as the total number of days between the day of admission and the day of discharge , or the last day of the stable dosing period ( day 140 ) if the patient remained in treatment beyond the stable dosing period . Compliance with treatment was assessed through treatment attendance , the number of days medicated divided by days in treatment , and counseling contacts , which were based on the length ( minutes ) and number of contacts the patient had with either individual or group treatments . Urine Testing Patients provided a supervised urine sample for toxicology screening three times per week . Sample s were tested on-site using EMIT ( Syva Corporation , Palo Alto , California ) for the presence of opioids , cocaine , and benzodiazepines ; and cut-off calibration concentrations were set at 300 g/mL for each test ( morphine , benzoylecgonine , oxazepam ) . The specificity of the EMIT system ranges from 96 % to 100 % . One sample each week was r and omly selected to be sent to an outside laboratory for thin-layer chromatography analysis , which detects these same compounds and a wide variety of other less commonly abused substances . Data Analysis Retention to week 20 , days in treatment , percentage of days attended , and amount of counseling contact time were analyzed with a one-way analysis of variance with methadone dose as the grouping factor and the Tukey Honestly Significant Difference ( HSD ) test was used for post hoc analyses . Comparisons for which the critical difference value corresponding to P < 0.05 are reported as significant for this and all subsequently described analyses . Treatment survival curves were compared using the Lee-Desu statistic , with pairwise comparisons between each of the three treatment groups . The percentages of urine positive for opioids , cocaine , benzodiazepines , and any other drugs were calculated for each patient through the end of the stable dosing period . A one-factor analysis of variance with methadone dose as the grouping factor was used for each of these analyses . Results Table 1 shows the demographic features of the 247 patients enrolled in the study . The only difference across the three treatment groups on any variable was marital status ; 8 % of the patients in the 50-mg treatment group were married compared to 17 % in the 20-mg and 25 % in the 0-mg groups . Table 1 . Demographic Characteristics for Patients ( n = 247 ) Assigned to Different Methadone Doses * Treatment Retention and Compliance Orderly dose effects were seen for survival in treatment ( Figure 2 ) . Although the three treatment groups had similar rates of retention during the first 4 weeks of treatment , when all participants were receiving active methadone , retention rates diverged between weeks 4 and 8 and dose effects were seen from weeks 8 through 20 . In the survival analysis , there was an overall difference between the three curves ( P < 0.01 ) , and pairwise comparison between the 50-mg and 0-mg treatment groups differed significantly ( P < 0.01 ) ; the differences between the 50-mg and 20-mg , and 20-mg and 0-mg treatment groups approached significance ( P = 0.1 and P = 0.08 , respectively ) . At week 20 , the end of the stable dosing period , retention was 52.4 % for the 50-mg , 41.5 % for the 20-mg , and 21.0 % for the 0-mg groups ( 50 versus 0 and 20 versus 0 , P < 0.05 ; 50 versus 20 , P > 0.05 ) . Figure 2 . Retention in treatment . n The number of days retained in treatment was also dose related ( P < 0.01 ) ; Buprenorphine at 2 mg and 6 mg daily was compared with methadone at 35 mg and 65 mg during 24 weeks of maintenance among 125 opioid-dependent patients . As hypothesized , 6 mg of buprenorphine were superior to 2 mg of buprenorphine in reducing illicit opioid use , but higher dosage did not improve treatment retention . Self-reported illicit opioid use declined substantially in all groups , but by the third month , significantly more heroin abuse was reported at 2 mg than at 6 mg of buprenorphine or of methadone . From an initial average of $ 1860/month , month 3 usage dropped to $ 41 ( methadone 65 mg ) , $ 73 ( methadone 35 mg ) , $ 118 ( buprenorphine 6 mg ) , and $ 35I/month ( buprenorphine 2 mg ) . Days of use also dropped from 29 days to 1.7 ( methadone 65 mg ) , 2.8 ( methadone 35 mg ) , 4.0 ( buprenorphine 6 mg ) , and 6.6 days/month ( buprenorphine 2 mg ) . This relatively low efficacy for 2 mg of buprenorphine persisted through month 6 of the trial , with 7.2 days/month and $ 235/month of use for buprenorphine at 2 mg versus 1.9 days/month and $ 65/month for the other three groups . Increased opioid abuse also was associated with significantly greater and persistent opioid withdrawal symptoms . Our secondary hypothesis , that buprenorphine would be equivalent to methadone in efficacy , was not supported . Treatment retention was significantly better on methadone ( 20 us . 16 weeks ) , and methadone patients had significantly more opioid-free urines ( 51 % vs. 26 % ) . Abstinence for at least 3 weeks was also more common on methadone than buprenorphine ( 65 % vs. 27 % ) . Thus , methadone was clearly superior to these two buprenorphine doses , but illicit opioid use was reduced more by higher than lower buprenorphine dosage . Future studies need to examine higher sublingual buprenorphine doses of 12 mg to 20 mg daily for potential efficacy CONTEXT Despite evidence that methadone maintenance treatment ( MMT ) is effective for opioid dependence , it remains a controversial therapy because of its indefinite provision of a dependence-producing medication . OBJECTIVE To compare outcomes of patients with opioid dependence treated with MMT vs an alternative treatment , psychosocially enriched 180-day methadone-assisted detoxification . DESIGN R and omized controlled trial conducted from May 1995 to April 1999 . SETTING Research clinic in an established drug treatment service . PATIENTS Of 858 volunteers screened , 179 adults with diagnosed opioid dependence were r and omized into the study ; 154 completed 12 weeks of follow-up . INTERVENTIONS Patients were r and omized to MMT ( n = 91 ) , which required 2 hours of psychosocial therapy per week during the first 6 months ; or detoxification ( n = 88 ) , which required 3 hours of psychosocial therapy per week , 14 education sessions , and 1 hour of cocaine group therapy , if appropriate , for 6 months , and 6 months of ( nonmethadone ) aftercare services . MAIN OUTCOME MEASURES Treatment retention , heroin and cocaine abstinence ( by self-report and monthly urinalysis ) , human immunodeficiency virus ( HIV ) risk behaviors ( Risk of AIDS Behavior scale score ) , and function in 5 problem areas : employment , family , psychiatric , legal , and alcohol use ( Addiction Severity Index ) , compared by intervention group . RESULTS Methadone maintenance therapy result ed in greater treatment retention ( median , 438.5 vs 174.0 days ) and lower heroin use rates than did detoxification . Cocaine use was more closely related to study dropout in detoxification than in MMT . Methadone maintenance therapy result ed in a lower rate of drug-related ( mean [ SD ] at 12 months , 2.17 [ 3.88 ] vs 3.73 [ 6.86 ] ) but not sex-related HIV risk behaviors and in a lower severity score for legal status ( mean [ SD ] at 12 months , 0.05 [ 0.13 ] vs 0.13 [ 0.19 ] ) . There were no differences between groups in employment or family functioning or alcohol use . In both groups , monthly heroin use rates were 50 % or greater , but days of use per month dropped markedly from baseline . CONCLUSIONS Our results confirm the usefulness of MMT in reducing heroin use and HIV risk behaviors . Illicit opioid use continued in both groups , but frequency was reduced . Results do not provide support for diverting re sources from MMT into long-term detoxification AIMS Opioid-dependent out patients may be more likely to present for pharmacological treatment if less than daily dosing can be arranged . These studies compared opioid withdrawal symptoms during 24- , 72- , and 120-hour buprenorphine dosing regimens and evaluated participants ' preferences for these different dosing regimens . PARTICIPANTS Thirty-three opioid-dependent participants received daily sublingual maintenance doses of 4 mg/70 kg ( n = 14 ) or 8 mg/70 kg ( n = 19 ) of liquid buprenorphine . METHODS In Study I participants received , in a r and om order , three dosing regimens for five repetitions of each : daily maintenance doses every 24 hours ( 4 or 8 mg/70 kg ) , triple the daily maintenance dose every 72 hours ( 12 or 24 mg/70 kg ) and quintuple the daily maintenance dose every 120 hours ( 20 or 40 mg/70 kg ) . Doses were administered under double-blind procedures , and placebos were administered on the interposed days during the latter two regimens . Subjective and observer ratings of opioid withdrawal symptoms were assessed daily prior to receipt of each dose . In Study II , a new group of participants received each of the three dosing regimens under open-dosing procedures and then chose between the different dosing regimens . FINDINGS Opioid withdrawal symptoms increased significantly during the every-fifth-day dosing regimen in both the blind- and open-dosing studies . In the choice phase of Study II , only one participant ( 7 % ) chose quintuple-every-fifth-day dosing over all other dosing options . CONCLUSIONS These results suggest that the maximum duration of action of buprenorphine is less than 5 days when five times the daily maintenance dose is provided AIMS To assess the efficacy of buprenorphine compared with methadone maintenance therapy for opioid dependence in a large sample using a flexible dosing regime and the marketed buprenorphine tablet . DESIGN Patients were r and omized to receive buprenorphine or methadone over a 13-week treatment period in a double-blind , double-dummy trial . SETTING Three methadone clinics in Australia . PARTICIPANTS Four hundred and five opioid-dependent patients seeking treatment . INTERVENTION Patients received buprenorphine or methadone as indicated clinical ly using a flexible dosage regime . During weeks 1 - 6 , patients were dosed daily . From weeks 7 - 13 , buprenorphine patients received double their week 6 dose on alternate days . MEASUREMENTS Retention in treatment , and illicit opioid use as determined by urinalysis . Self-reported drug use , psychological functioning , HIV-risk behaviour , general health and subjective ratings were secondary outcomes . FINDINGS Intention-to-treat analyses revealed no significant difference in completion rates at 13 weeks . Methadone was superior to buprenorphine in time to termination over the 13-week period ( Wald chi 2 = 4.371 , df = 1 , P = 0.037 ) , but not separately for the single-day or alternate-day dosing phases . There were no significant between-group differences in morphine-positive urines , or in self-reported heroin or other illicit drug use . The majority ( 85 % ) of the buprenorphine patients transferred to alternate-day dosing were maintained in alternate-day dosing . CONCLUSIONS Buprenorphine did not differ from methadone in its ability to suppress heroin use , but retained approximately 10 % fewer patients . This poorer retention was due possibly to too-slow induction onto buprenorphine . For the majority of patients , buprenorphine can be administered on alternate days Abstract Rationale : Administration of double the maintenance dose of buprenorphine has been shown to permit every-other-day dosing . Whether longer periods between dosing can be achieved is unknown . Objectives : To examine whether triple the maintenance dose can be administered every 72 h without opioid withdrawal or intoxication . Methods : Sixteen opioid-dependent out patients each received three conditions ( 1 ) the maintenance dose of buprenorphine every 24 h , ( 2 ) double the maintenance dose every 48 h , and ( 3 ) triple the maintenance dose every 72 h under double-blind placebo-controlled conditions . Each conditions was imposed in a r and om sequence for 21–22 days . Self report and observer measures were taken at 24-h intervals . Results : No significant differences were observed on measures of opioid agonist and withdrawal effects between the dosing conditions . However , averaging effects across conditions may obscure important within-condition effects . When conditions were analyzed by individual days within a condition , several significant effects were observed . For example , 24 h after administration of triple the maintenance dose , significant effects were observed in eight opioid agonist measures . Also , 72 h after administration of triple the maintenance dose , significant effects were observed on four measures of withdrawal . Neither adverse medical reactions nor excessive opioid intoxication were observed . Conclusions : These results suggest that buprenorphine may be administered safely every 72 h by tripling the maintenance dose , with only minimal withdrawal complaints . Importantly , this 72-h dosing may permit patients to attend clinic thrice weekly without the use of take-home doses Thirteen opioid-dependent out patients participated in a double-blind , placebo-controlled , crossover trial . Twenty-one days of daily sublingual buprenorphine administration were compared to 21-days of alternate-day buprenorphine administration where patients received twice their daily maintenance dose every other day with placebo on the interposed day . Observer- and subject-rated measures of opioid agonist and withdrawal effects , pupillary diameter , and dose identification s were collected daily . Ten subjects ( 77 % ) completed the study ( n = 6 , 4 mg/70 kg ; n = 4 , 8 mg/70 kg ) ; 8 subjects ( 62 % ) participated in a second crossover . Sixteen of seventeen measures of opioid agonist and withdrawal effects obtained during alternate-day administration did not differ significantly from those obtained during daily dosing in the ten subjects completing the study . The only significant difference observed was in subject-rated agonist effects , which were significantly lower during alternate-day than daily administration . No differences were observed between treatments on any measure for the eight subjects completing a second crossover . These data suggest that buprenorphine can be administered safely every 48 hours by doubling the maintenance dose . This alternate-day schedule permits patients to attend the clinic less frequently without the risk of diversion associated with take-home doses , may be cost-effective for programs , and may be useful in setting s in which travel to the clinic is a barrier to treatment BACKGROUND Buprenorphine is a promising alternative to methadone or levo-acetyl alpha methadol for opioid agonist maintenance treatment , and thrice-weekly dosing would facilitate its use for this purpose . METHODS After a 3-day induction , opioid-dependent patients ( n = 92 ) were r and omly assigned to daily clinic attendance and 12-weeks maintenance treatment with sublingual buprenorphine administered double blind either daily ( n = 45 ; 16 mg/70 kg ) or thrice weekly ( n = 47 ; 34 mg/70 kg on Fridays and Sundays and 44 mg/70 kg on Tuesdays ) . Outcome measures include retention , results of 3x/week urine toxicology tests , and weekly self-reported illicit drug use . RESULTS There were no significant differences at baseline in important social , demographic , and drug-use features . Retention was 71 % in the daily and 77 % in the 3x/week conditions . The proportion of opioid-positive urine tests decreased significantly from baseline in both groups and averaged 57 % ( daily ) and 58 % in 3x/week . There were no significant differences between groups in self-reported number of bags of heroin used for any day of the week , including Thursdays ( 48 - 72 hours following the last buprenorphine dose for subjects in the 3x/week condition ) , or in medication compliance ( 92 % , 91 % ) and counseling attendance ( 82 % , 82 % ) . CONCLUSIONS At an equivalent weekly dose of 112 mg/70 kg , thrice-weekly and daily sublingual buprenorphine appear comparable in efficacy with regard to retention and reductions in illicit opioid and other drug use . These findings support the potential for utilizing thrice-weekly buprenorphine dosing in novel setting AIMS To evaluate the effect of a 4 mg/day sublingual dose of buprenorphine in the maintenance treatment of opium dependence in comparison with a 1 mg/day dose over an 18-week treatment period . As a secondary objective , the results were determined concurrently for subjects treated with a 2 mg/day dose . DESIGN Subjects were assigned r and omly to three dosage groups . PARTICIPANTS 330 consecutive ( 320 men and 10 women ) opium addicts who met the DSM-IV criteria for opioid dependence and were seeking treatment . INTERVENTION Subjects received a 1 , 2 or 4 mg/day dose of buprenorphine and were treated in an outpatient clinic where they also received a weekly 1-hour clinical counseling session . MEASUREMENTS Addiction Severity Index , retention in treatment , and illegal opioid use as determined by r and om urine testing . FINDINGS The mean age was 37.5 years ( SD=11.4 , range 19 - 72 ) . Overall , 194 ( 58.8 % ) of the patients completed the 18 week study . Completion rates by dosage groups were 47.3 % for the 1 mg group , 58.2 % for the 2 mg group and 70.9 % for the 4 mg group ( chi(2)=12.7 , df=2 , P=0.0017 ) . CONCLUSIONS The results support the efficacy and safety of buprenorphine for opium addiction and suggest that an adequate dose of buprenorphine would help to increase the success rate BACKGROUND Relapse to drug use is often seen when contingencies design ed to reduce drug use are discontinued . This paper reports on a stepdown maintenance contingency and 1-year follow-up in 110 patients who were maintained on methadone ( 50 or 70 mg/day ) and who had completed a contingency management trial targeted to decreasing their opiate use . In the prior study ( induction phase , 8 weeks ) participants received vouchers for each opiate-negative urine screen or noncontingently . METHODS In this study ( maintenance phase , 12 weeks ) , participants were rer and omized to receive vouchers and take-home methadone doses contingent on providing opiate-negative urine specimens ( N=55 ) or noncontingently ( N=55 ) . Since participants had been rer and omized from induction-phase contingencies , most study data were analyzed as if from a 2 x 2 ( inductionxmaintenance ) design . Follow-up interviews were conducted at 3 , 6 , and 12 months after study participation . RESULTS Patients who received the maintenance contingency following an 8-week induction contingency had better outcomes than those who received noncontingent incentives in either the maintenance or induction phases of the trial . Good outcome at follow-up was predicted by enrollment in methadone maintenance after the study . Significantly more participants in the maintenance contingency group transferred directly to another methadone program . CONCLUSION These findings support the therapeutic value of extending the duration of contingency management and long-term methadone maintenance BACKGROUND Buprenorphine is a partial agonist at the mu-opioid receptor that has been proposed as an alternative to traditional full agonist maintenance therapy for the treatment of opioid addiction . We report on a clinical trial in which the relative safety and efficacy of long-term fixed-dose buprenorphine maintenance was examined in comparison to low- and high-dose methadone maintenance . METHODS Two hundred twenty-five treatment-seeking opioid addicts ( 46 women , 179 men ) were r and omly assigned to receive , in a double-blind manner , either 8 mg/d of buprenorphine , 30 mg/d of methadone , or 80 mg/d of methadone maintenance over a 1-year period . Objective and subjective measures of efficacy ( urine toxicology , retention , craving , and withdrawal symptoms ) were examined at the study midpoint and at termination , and safety data were tabulated over the entire 52-week study period . RESULTS Patients assigned to high-dose methadone maintenance performed significantly better on measures of retention , opioid use , and opioid craving than either the low-dose methadone or the buprenorphine group at both 26-week and 52-week time points . Performance on these measures was virtually identical between the latter two groups . No serious adverse health effects attributable to buprenorphine were noted . CONCLUSIONS Buprenorphine maintenance at 8 mg/d appears to be less than optimally efficacious under the conditions of the present study . Continued research is needed to reconcile these findings with the more positive results reported by other investigative groups . There are no apparent health risks associated with long-term buprenorphine maintenance at this dosage BACKGROUND Opioid dependence is a chronic , relapsing disorder with important public health implication s. METHODS In a 17-week r and omized study of 220 patients , we compared levomethadyl acetate ( 75 to 115 mg ) , buprenorphine ( 16 to 32 mg ) , and high-dose ( 60 to 100 mg ) and low-dose ( 20 mg ) methadone as treatments for opioid dependence . Levomethadyl acetate and buprenorphine were administered three times a week . Methadone was administered daily . Doses were individualized except in the group assigned to low-dose methadone . Patients with poor responses to treatment were switched to methadone . RESULTS There were 55 patients in each group ; 51 percent completed the trial . The mean ( + /-SE ) number of days that a patient remained in the study was significantly higher for those receiving levomethadyl acetate ( 89+/-6 ) , buprenorphine ( 96+/-4 ) , and high-dose methadone ( 105+/-4 ) than for those receiving low-dose methadone ( 70+/-4 , P<0.001 ) . Continued participation was also significantly more frequent among patients receiving high-dose methadone than among those receiving levomethadyl acetate ( P=0.02 ) . The percentage of patients with 12 or more consecutive opioid-negative urine specimens was 36 percent in the levomethadyl acetate group , 26 percent in the buprenorphine group , 28 percent in the high-dose methadone group , and 8 percent in the low-dose methadone group ( P=0.005 ) . At the time of their last report , patients reported on a scale of 0 to 100 that their drug problem had a mean severity of 35 with levomethadyl acetate , 34 with buprenorphine , 38 with high-dose methadone , and 53 with low-dose methadone ( P=0.002 ) . CONCLUSIONS As compared with low-dose methadone , levomethadyl acetate , buprenorphine , and high-dose methadone substantially reduce the use of illicit opioids Clinical trials carried out to compare methadone and buprenorphine in the treatment of opioid dependence have generally employed an alcoholic solution of buprenorphine , which has a bioavailability superior to that of the tablets . Since the product available for large scale use is in tablet form , one intended to verify the efficacy of this formulation . In a multicentre r and omised controlled double blind study , 72 opioid dependent patients were assigned to treatment with buprenorphine ( 8 mg/day ) or methadone ( 60 mg/day ) for a period of 6 months . The two compounds did not show any significant difference with regard to urinalyses : the average percentage of analyses proving negative was 60.4 % for patients assigned to buprenorphine , and 65.5 % for those assigned to methadone . With regard to retention , a non-significant trend in favour of methadone was observed . Patients completing the trial improved significantly in terms of psychosocial adjustment and global functioning , as ascertained by the DSM-IV-GAF and symptom checklist-90 ( SCL-90 ) scales , and this was independent of the treatment group . Finally , in the case of buprenorphine , patients who dropped out differed significantly from those who stayed , in terms of a higher level of psychopathological symptoms , and a lower level of psychosocial functioning . The results of the study further support the utility of buprenorphine for the treatment of opioid dependence This study investigated conditions under which methadone patients with urinalysis evidence of persistent multiple drug abuse would respond to take-home incentive procedures . Study subjects su bmi tted > or = 80 % opiate and /or cocaine positive urines during a 5-week baseline period ( M , W , F urine testing ) while maintained on 60 mg methadone . Doses were raised to 80 - 100 mg methadone under blind conditions and subjects were r and omly assigned to receive methadone take-home doses under one of three conditions : ( a ) earn a 1-day take-home privilege for each opiate and cocaine-free test delivered ( daily contingent condition ) , ( b ) three negative test results required for the first take-home privilege , with each subsequent negative test earning one take-home dose ; a positive test reset the contingency back to three again ( weekly contingent condition ) , or ( c ) a control group that did not receive take-home privileges ( no take-home control ) . Five of 21 subjects ( 24 % ) assigned to a contingent take-home intervention ( 2 from condition a , 3 from condition b ) showed marked reductions in drug use and delivered 4 or more consecutive weeks of drug-free urines during a 16-week intervention . No subject in the control group met these criteria . Percent positive urines decreased by 14 % and 18 % from baseline in daily and weekly contingency groups , respectively , compared to a decline of 2 % in the no take-home control group ( planned contrast of means p < .07 and .05 , respectively ) . Thus , the study demonstrated that take-home incentives can be effective for reducing during-treatment use of opiates and cocaine in methadone patients with a poor prognosis related to their persistent multiple drug use Eighty-five heroin addicts who were unwilling to receive methadone maintenance or enter therapeutic communities were assessed , single-blind , for the lowest sublingual dose of buprenorphine that blocked heroin craving ( 8.0 mg max ) . All doses were administered daily under observation . After maintenance for 4 to 12 weeks , abstinent subjects ( confirmed by urine drug screens ) entered a double-blind discontinuation trial and were r and omly assigned to receive dose reductions ( 10 % twice weekly for 5 weeks to zero dose , then placebo for 2 weeks ) or a stable dose for 7 weeks . Subjects were terminated from discontinuation if heroin was used or they had increased craving/symptoms . Subjects completed the trial if they did not use heroin and had no increase in craving/symptoms . A wide dose range ( 1.5 - 8.0 mg/day ) was effective in reducing heroin craving and use . Of 73 subjects who received buprenorphine for 4 to 52 weeks , 40 had no prior treatment , despite high levels ( mean $ /day heroin = 70.5 + /- 94.7 ) and many years ( mean years = 10.7 + /- 8.6 ) of dependence . Subjects who received dose reductions developed abstinence symptoms , low energy most commonly , associated with drug-seeking behavior . Discontinuation trial outcome ( n = 51 ) shows a highly significant difference between 29 subjects who received dose reductions ( 28 terminated , 1 completed ) and 22 subjects who received no dose reductions ( 3 terminated ; 19 completed ) ( chi-square = 36.08 ; p less than .00001 ) . The findings suggest that buprenorphine could be an important medication for reducing dem and for heroin by many heroin addicts who remain outside the present health-care system . ( ABSTRACT TRUNCATED AT 250 WORDS Large-scale placebo controlled clinical trials assessing the efficacy of medications for the treatment of drug dependence have generally been limited to alcohol , cocaine and nicotine dependent population s. The purpose of the present study was to assess the early ( 1 - 2 week ) clinical effectiveness of buprenorphine versus placebo in an opioid dependent population . The study used a parallel-group design with a behavioral choice component to compare buprenorphine ( a mu-opioid partial agonist ) to placebo for the treatment of opioid dependence . Opioid dependent volunteer patients participated in a 14-day study to assess the effectiveness and patient acceptance of this new pharmacotherapy for the treatment of opioid dependence . Patients were r and omly assigned to placebo ( n = 60 ) or 2 mg ( n = 60 ) or 8 mg ( n = 30 ) daily sublingual buprenorphine . All doses were administered double-blind . On days 6 - 13 all patients could request a dose change , knowing that their new dose would be r and omly chosen from the remaining 2 alternatives . Compared to placebo , patients given buprenorphine ( independent of dose ) showed greater time on initial dose , requested fewer dose changes , used less illicit opioids ( assessed by urinalysis ) , and rated dose adequacy higher . These results demonstrate that a placebo controlled study with a behavioral choice component is an effective means of assessing the potential efficacy and acceptability of new pharmacotherapies for opioid dependence BACKGROUND Buprenorphine , a partial mu-agonist and kappa-antagonist , has been proposed as an alternative to methadone for maintenance treatment of opioid dependence , especially for patients with concurrent cocaine dependence or abuse . This study evaluated whether higher maintenance doses of buprenorphine and methadone are superior to lower doses for reducing illicit opioid use and whether buprenorphine is superior to methadone for reducing cocaine use . METHODS A total of 116 subjects were r and omly assigned to 1 of 4 maintenance treatment groups involving higher or lower daily doses of sublingual buprenorphine ( 12 or 4 mg ) or methadone ( 65 or 20 mg ) in a double-blind , 24-week clinical trial . Outcome measures included retention in treatment and illicit opioid and cocaine use as determined by urine toxicology testing and self-report . RESULTS There were significant effects of maintenance treatment on rates of illicit opioid use , but no significant differences in treatment retention or the rates of cocaine use . The rates of opioid-positive toxicology tests were lowest for treatment with 65 mg of methadone ( 45 % ) , followed by 12 mg of buprenorphine ( 58 % ) , 20 mg of methadone ( 72 % ) , and 4 mg of buprenorphine ( 77 % ) , with significant contrasts found between 65 mg of methadone and both lower-dose treatments and between 12 mg of buprenorphine and both lower-dose treatments . CONCLUSIONS The results support the superiority of higher daily buprenorphine and methadone maintenance doses vs lower doses for reducing illicit opioid use , but the results do not support the superiority of buprenorphine compared with methadone for reducing cocaine use The aim of this study was to assess the efficacy of 1- , 2- , and 4-mg-per-day sublingual doses of buprenorphine in the maintenance treatment of heroin-dependent patients over a 17-week treatment period . Subjects were r and omized to three dosage groups . Participants consisted of 105 heroin addicts ( 102 men and 3 women ) who met the DSM-IV criteria for opioid dependence and were seeking treatment . Subjects received buprenorphine at a dose of 1 , 2 , or 4 mg per day and were treated in an urban outpatient clinic , including a weekly 1-hour individual counseling session . Days retained in treatment were measured . Overall , 49 patients ( 46.7 % ) completed the 17-week study . Completion rates by dosage group were 34.3 % for the 1 mg dose group , 42.9 % for the 2 mg dose group , and 62.9 % for the 4 mg dose group . Retention in the 4 mg dose group was significantly better than in the 1 mg dose group ( P = .017 ) . None of the other comparisons was significant . The results support the efficacy and safety of buprenorphine for outpatient treatment of heroin dependence and seem to indicate that the highest dose ( 4 mg ) of buprenorphine was the best of the three doses for Iranian heroin addicts to increase their retention in treatment Two studies utilized within-subjects design s to determine whether take-home methadone doses can reinforce adjunct therapy attendance of drug abuse patients . These studies varied the reinforcement density and the schedule of methadone take-home doses . In Study 1 , patients ( n = 10 ) either could or could not receive a take-home following each therapy session . Study 2 patients ( n = 15 ) could either earn take-homes following each therapy session attended ( i.e. , 2 take-homes per week ) or could earn one take-home dose following each attendance to two consecutive sessions attended . In both studies experimental conditions alternated during three-week blocks of time . Across studies , any reinforcement by take-home doses produced more attendance at therapy sessions than that observed in the no reinforcement condition . Take-home incentive effects were strongest when each of the two weekly therapy sessions was reinforced by a methadone take-home dose . Increased attendance was not associated with reduced drug use , due perhaps to high rates of pre- study drug use and limited therapy duration . Contemporary opioid abusers present with multiple problems that methadone was never intended to treat . The present studies illustrate a method by which methadone treatment can improve the likelihood of delivering other services that may prove effective in treating some of these problems OBJECTIVE To compare the clinical efficacy of different doses of levomethadyl acetate hydrochloride ( known as LAAM ) in the treatment of opioid dependence . DESIGN A r and omized controlled , double-blind , parallel group , 17-week study . SETTING Outpatient facilities at Johns Hopkins University Bayview Medical Center , Baltimore , Md. PATIENTS Opioid-dependent volunteers ( N=180 ) applying to a treatment- research clinic . INTERVENTION Thrice-weekly ( Monday/Wednesday/Friday ) oral LAAM dose conditions of 25/25/35 mg , 50/50/70 mg , and 100/100/140 mg and nonm and atory counseling . MAIN OUTCOME MEASURES Retention in treatment , self-reported heroin use , and opioid-positive urine specimens . RESULTS Retention was independent of subjects ' sex and dose . Self-reported heroin use decreased in a dose-related manner . At final assessment , patients in the high-dose condition reported using heroin 2.5 of 30 days as compared with 4.1 or 6.3 days for patients in the medium-dose and low-dose conditions , respectively ( high dose vs low dose , P<.05 ) ; urinalysis results were similarly dose related . Overall , 20 ( 34 % ) of 59 patients in the high-dose condition remained opioid-abstinent for 4 consecutive weeks , as compared with 8 ( 14 % ) of 59 in the medium-dose and 7 ( 11 % ) of 62 in the low-dose conditions ( P<.01 ) . Self-report and urinalysis data are consistent with a greater than 90 % reduction in illicit opioid use by the high-dose group relative to pretreatment levels . CONCLUSION Opioid substitution treatment with LAAM substantially reduces illicit opioid use . The clinical efficacy of LAAM is positively related to dose Rationale : Buprenorphine can decrease opioid self-administration by humans and animals , but its ability to decrease drug-seeking behavior and craving ( i.e. motivational measures ) among outpatient volunteers using clinical ly relevant dosing schedules has not been extensively studied . Objectives : We investigated whether daily versus alternating-day administration of high versus low buprenorphine doses influenced choice of , and operant responding for , hydromorphone versus money . Methods : Fourteen heroin-dependent out patients were maintained under four buprenorphine sublingual tablet ( double blind ) dose conditions using a within-subject , r and omized crossover design . All participants received , for 2 weeks each , buprenorphine doses of 2 mg daily , 4 mg/placebo on alternating days , 16 mg daily , and 32 mg/placebo on alternating days . In each laboratory test session , participants chose between money ( $ 2/choice ) and drug ( 1/8 of total hydromorphone , 4 or 24 mg IM in different sessions ) alternatives using an eight-trial non-independent progressive ratio schedule ( FR 100 , 200 , ... 12,800 ) . The drug dose and money amount earned was delivered after the end of the 2.5-h work period . Results : Hydromorphone 24 mg was more reinforcing than 4 mg . Higher versus lower average buprenorphine doses ( regardless of daily versus alternate-day schedule ) significantly decreased hydromorphone 24 mg choice and increased money choice . Baseline heroin craving question naire scores predicted drug choice , and craving scores were significantly decreased by high-dose buprenorphine . Conclusions : High-dose buprenorphine attenuated opioid drug-seeking behavior , heroin craving self-reports and increased sensitivity to alternative reinforcement . These beneficial effects were retained when high-dose buprenorphine was administered on alternate days CONTEXT Methadone hydrochloride treatment is the most common pharmacological intervention for opioid dependence , and recent interest has focused on exp and ing methadone treatment availability beyond traditional specially licensed clinics . However , despite recommendations regarding effective dosing of methadone , controlled clinical trials of higher-dose methadone have not been conducted . OBJECTIVE To compare the relative clinical efficacy of moderate- vs high-dose methadone in the treatment of opioid dependence . DESIGN A 40-week r and omized , double-blind clinical trial starting in June 1992 and ending in October 1995 . SETTING Outpatient substance abuse treatment research clinic at the Johns Hopkins University Bayview Campus , Baltimore , Md. PARTICIPANTS One hundred ninety-two eligible clinic patients . INTERVENTION Daily oral methadone hydrochloride in the dose range of 40 to 50 mg ( n = 97 ) or 80 to 100 mg ( n = 95 ) , with concurrent substance abuse counseling . MAIN OUTCOME MEASURES Opioid-positive urinalysis results and retention in treatment . RESULTS By intent-to-treat analysis through week 30 patients in the high-dose group had significantly lower rates of opioid-positive urine sample s compared with patients in the moderate-dose group ( 53.0 % [ 95 % confidence interval [ CI ] , 46.9%-59.2 % ] vs 61.9 % [ 95 % CI , 55.9%-68.0 % ] ; P = .047 . These differences persisted during withdrawal from methadone . Through day 210 no significant difference was evident between dose groups in treatment retention ( high-dose group mean retention , 159 days ; moderate-dose group mean retention , 157 days ) . Nineteen ( 33 % ) of 57 patients in the high-dose group and 11 ( 20 % ) of 54 patients in the moderate-dose group completed detoxification . CONCLUSIONS Both moderate- and high-dose methadone treatment result ed in decreased illicit opioid use during methadone maintenance and detoxification . The high-dose group had significantly greater decreases in illicit opioid use OBJECTIVE To assess the efficacy of buprenorphine for short-term maintenance/detoxification . DESIGN A r and omized , double-blind , parallel group study comparing buprenorphine , 8 mg/d , methadone , 60 mg/d , and methadone , 20 mg/d , in a 17-week maintenance phase followed by an 8-week detoxification phase . SETTING Outpatient facilities at the Addiction Research Center , Baltimore , Md. PATIENTS One hundred sixty-two volunteers seeking treatment for opioid dependence . INTERVENTION In addition to the medication , counseling using a relapse prevention model was offered but not required . PRIMARY OUTCOME MEASURES Retention time in treatment , urine sample s negative for opioids , and failure to maintain abstinence . RESULTS Throughout the maintenance phase , retention rates were significantly greater for buprenorphine ( 42 % ) than for methadone , 20 mg/d ( 20 % , P less than .04 ) ; the percentage of urine sample s negative for opioids was significantly greater for buprenorphine ( 53 % , P less than .001 ) and methadone , 60 mg/d ( 44 % , P less than .04 ) , than for methadone , 20 mg/d ( 29 % ) . Failure to maintain abstinence during the maintenance phase was significantly greater for methadone , 20 mg/d , than for buprenorphine ( P less than .03 ) . During the detoxification phase , no differences were observed between groups with respect to urine sample s negative for opioids . For the entire 25 weeks , retention rates for buprenorphine ( 30 % , P less than .01 ) and methadone , 60 mg/d ( 20 % , P less than .05 ) , were significantly greater than for methadone , 20 mg/d ( 6 % ) . All treatments were well tolerated , with similar profiles of self-reported adverse effects . The percentages of patients who received counseling did not differ between groups . CONCLUSIONS Buprenorphine was as effective as methadone , 60 mg/d , and both were superior to methadone , 20 mg/d , in reducing illicit opioid use and maintaining patients in treatment for 25 weeks This study compared 24‐ , 48‐ , 72‐ , and 96‐hour buprenorphine dosing regimens in opioid‐dependent out patients AIMS To assess the acute-on-chronic effects of methadone on drug craving , mood and cognitive and psychomotor functioning in patients on long-term methadone substitution treatment . DESIGN AND PARTICIPANTS A double-blind , cross-over design was used to compare the effects of a 33 % increase in patient 's daily dosage of methadone with a matched placebo linctus . Eighteen patients completed the study ; all were assessed pre- and post-drug on two separate testing days . FINDINGS Methadone significantly increased both positive craving ( expected positive effects ) and negative craving ( expected relief of withdrawal discomfort ) for heroin . Patients were unable to distinguish between methadone and placebo treatments . No differences between treatments emerged in cognitive or psychomotor effects . In terms of mood , patients were more alert and more contented following placebo than following methadone . CONCLUSIONS Additional methadone may " prime " cravings for heroin in methadone substitution patients Abstract Alternate-day buprenorphine dosing was compared to daily dosing in opioid-dependent out patients and choice of alternate-day versus daily dosing was assessed . Four dosing schedules were presented in r and om order under blind and open dosing conditions . Subjects received two exposures to each dosing schedule . During daily dosing , subjects received maintenance doses every 24 h. During blind alternate-day dosing , subjects received double maintenance doses every 48 h ; placebo was interposed on intervening days . During open alternate-day dosing , subjects received twice their maintenance dose on Monday , Wednesday and Friday and maintenance doses on Sunday . After completing two exposures to each dosing schedule , subjects chose either daily or alternate-day schedules each week for 1 month . Study participation was contingent on daily attendance and opioid abstinence . Ten subjects were exposed to the four conditions once . Seven subjects repeated these conditions and participated in the choice phase . The effects of daily versus alternate-day dosing were not influenced by blind or open dosing conditions . Subjects ’ ratings of withdrawal , “ sick ” and sedation were lower during daily than during alternate-day dosing , but the difference between treatments was small . Nonetheless , subjects still chose alternate-day dosing on 96 % of occasions , suggesting that the subject-rated differences between dosing schedules were not influential . These results extend prior findings to open-dosing conditions , and replicate the safety and acceptability of alternate-day buprenorphine treatment . Choice of alternate-day buprenorphine administration underscores the procedure ’s clinical utility and potential use as a positive reinforcer to enhance opioid treatment CONTEXT Methadone maintenance is an effective treatment for opioid dependence , yet its use is restricted to federally licensed narcotic treatment programs ( NTPs ) . Office-based care of stabilized methadone maintenance patients is a promising alternative but no data are available from controlled trials regarding this type of program . OBJECTIVE To determine the feasibility and efficacy of office-based methadone maintenance by primary care physicians vs in an NTP for stable opioid-dependent patients . DESIGN Six-month , r and omized controlled open clinical trial conducted February 1999-March 2000 . SETTING Offices of 6 primary care internists and an NTP . PATIENTS Forty-seven opioid-dependent patients who had been receiving methadone maintenance therapy in an NTP without evidence of illicit drug use for 1 year and without significant untreated psychiatric comorbidity were r and omized ; 1 patient refused to participate after treatment assignment to NTP . INTERVENTIONS Patients were r and omly assigned to receive office-based methadone maintenance from primary care physicians , who received specialized training in the care of opioid-dependent patients ( n = 22 ) , or usual care at an NTP ( n = 24 ) . MAIN OUTCOME MEASURES Illicit drug use , clinical instability ( persistent drug use ) , patient and clinician satisfaction , functional status , and use of health , legal , and social services , compared between the 2 groups . RESULTS Eleven of 22 ( 50 % ; 95 % confidence interval [ CI ] , 29%-71 % ) patients in office-based care compared with 9 of 24 ( 38 % ; 95 % CI , 21%-57 % ) of NTP patients had a self-report or urine toxicology test result indicating illicit opiate use ( P = .39 ) . Hair toxicology testing detected an additional 2 patients in each treatment group with evidence of illicit drug use , but this did not change the overall findings . Ongoing illicit drug use meeting criteria for clinical instability occurred in 4 of 22 ( 18 % ; 95 % CI , 7%-39 % ) patients in office-based care compared with 5 of 24 ( 21 % ; 95 % CI , 9%-41 % ) NTP patients ( P = .82 ) . Sixteen of the 22 ( 73 % ; 95 % CI , 54%-92 % ) office-based patients compared with 3 of the 24 ( 13 % ; 95 % CI , 0%-26 % ) NTP patients thought the quality of care was excellent ( P = .001 ) . There were no differences over time within or between groups in functional status or use of health , legal , or social services . CONCLUSIONS Our results support the feasibility and efficacy of transferring stable opioid-dependent patients receiving methadone maintenance to primary care physicians ' offices for continuing treatment and suggest guidelines for identifying patients and clinical monitoring The aim of this study was to assess the efficacy of methadone compared with buprenorphine maintenance therapy in heroin-dependent patients over a treatment period of 18 weeks . Subjects were r and omized to receive either methadone or buprenorphine in a comparative double-blind study and consisted of 164 heroin-dependent male patients who met the DSM-IV criteria for heroin dependence and were seeking treatment . The 164 subjects included 41 patients in 1-mg , 41 patients in 3-mg , and 41 patients in 8-mg dosage group of buprenorphine , and also 41 patients in the 30-mg dosage group of methadone . The mean age was 31.4 years for total buprenorphine group and 33.7 years for methadone group ( the mean age differences in 4 groups were not statistically significant ) . Subjects received buprenorphine at a dose of 1 , 3 , or 8 mg per day or methadone at a dose of 30 mg per day and were treated in an urban outpatient clinic , offering a 1-hour weekly individual counseling session . Days retained in treatment were measured . Completion rates by buprenorphine dosage group were 29.3 % for the 1-mg dose group , 46.3 % for the 3-mg dose group , 68.3 % for the 8-mg dose group , and 61 % for the 30-mg methadone dose group . Retention in the 8-mg dose group was significantly better than in the 1-mg dose group ( p=.00041 ) and in the 3-mg dose group ( p=.045 ) ; other comparison ( 1 mg dose with 3 mg dose ) was not significant . Methadone group was significantly better than 1 mg buprenorphine dose group ( p=.004 ) , but was not significantly different from 3 mg buprenorphine dose group ( p=.18 ) or 8 mg buprenorphine dose group ( p=.49 ) . The results support the efficacy of buprenorphine for outpatient treatment of heroin dependence and seem to indicate that the highest dose ( 8 mg ) of buprenorphine was the best of the three doses of buprenorphine , and also support the superiority of 30 mg of methadone compared to 1 mg dose of buprenorphine for Iranian heroin-dependent patients to increase their retention in treatment AIMS To compare opioid withdrawal symptoms during 24- , 48- , 72- and 96-hour buprenorphine dosing regimens and to evaluate subjects ' preferences for these different dosing schedules . SUBJECTS Fourteen opioid-dependent subjects participated in this study . They received daily sublingual maintenance doses of 4 mg/70 kg ( n = 4 ) or 8 mg/70 kg ( n = 10 ) of buprenorphine . INTERVENTION In the first study subjects received , in a r and om order , four dosing regimens for five repetitions of each : daily maintenance doses every 24 hours ( 4 or 8 mg/70 kg ) , double the daily maintenance dose every 48 hours ( 8 or 16 mg/70 kg ) , triple the daily maintenance dose every 72 hours ( 12 or 24 mg/70 kg ) , and quadruple the daily maintenance dose every 96 hours ( 16 or 32 mg/70 kg ) . Measures of subjective and observer opioid withdrawal symptoms were assessed prior to receipt of each dose . In a second study , subjects chose between the different dosing regimens . FINDINGS Some withdrawal ratings increased during the less frequent dosing schedules in the first study . In the second study , 46 % of subjects preferred the quadruple-every-fourth-day dosing regimen over every other option , and only 14 % preferred to be dosed daily . CONCLUSIONS These results suggest that some opioid-dependent out patients are willing and able to endure the withdrawal symptoms associated with less than daily dosing , and a twice-weekly dosing regimen may be possible AIMS To describe the level of involvement of general practitioners ( GPs ) in the management of illicit drug dependency ; nature of current practice in the management of illicit drug dependency ; influence of guidelines on practice ; GP training experience and needs ; and to consider the policy implication s of the findings . DESIGN A cross-sectional postal question naire survey . SETTING General practice in Scotl and . PARTICIPANTS A 1 : 4 r and omized sample ( n = 926 ) of general practice principals , stratified according to age , gender and number of practice partners . MEASUREMENTS A structured postal question naire . FINDINGS A 63 % response rate was achieved after two reminders ( n = 583 ) . Sixty per cent of respondents treated drug users , 51.5 % provided methadone maintenance but only 58 % used doses in the recommended range . Maintenance prescribing of dihydrocodeine and benzodiazepines was provided by 24 % and 44.8 % of respondents , respectively . While 79.3 % had received the national clinical guidelines only 22.5 % believed this had influenced their practice . Only a third of respondents had received drug dependency training . Beliefs about whether prescribing for drug misusers is part of a GPs professional remit was split . CONCLUSIONS There was relatively high involvement with drug users , with methadone maintenance being the most common treatment provided . Maintenance prescribing of dihydrocodeine and benzodiazepines were common despite a lack of clinical evidence supporting the effectiveness of these treatments . This may reflect the nature of the presenting drug problems and highlights the difficulties some GPs may face in managing multiple drug dependencies within current guidelines . Further local training to implement guidelines along with trials of alternative treatments currently outwith guidelines should be considered BACKGROUND Although methadone maintenance is an effective therapy for heroin dependence , some patients continue to use heroin and may benefit from therapeutic modifications . This study evaluated a behavioral intervention , a pharmacological intervention , and a combination of both interventions . METHODS Throughout the study all patients received daily methadone hydrochloride maintenance ( initially 50 mg/d orally ) and weekly counseling . Following baseline treatment patients who continued to use heroin were r and omly assigned to 1 of 4 interventions : ( 1 ) contingent vouchers for opiate-negative urine specimens ( n = 29 patients ) ; ( 2 ) methadone hydrochloride dose increase to 70 mg/d ( n = 31 patients ) ; ( 3 ) combined contingent vouchers and methadone dose increase ( n = 32 patients ) ; and ( 4 ) neither intervention ( comparison st and ard ; n = 28 patients ) . Methadone dose increases were double blind . Vouchers had monetary value and were exchangeable for goods and services . Groups not receiving contingent vouchers received matching vouchers independent of urine test results . Primary outcome measure was opiate-negative urine specimens ( thrice weekly urinalysis ) . RESULTS Contingent vouchers and a methadone dose increase each significantly increased the percentage of opiate-negative urine specimens during intervention . Contingent vouchers , with or without a methadone dose increase , increased the duration of sustained abstinence as assessed by urine screenings . Methadone dose increase , with or without contingent vouchers , reduced self-reported frequency of use and self-reported craving . CONCLUSIONS In patients enrolled in a methadone-maintainence program who continued to use heroin , abstinence reinforcement and a methadone dose increase were each effective in reducing use . When combined , they did not dramatically enhance each other 's effects on any 1 outcome measure , but they did seem to have complementary benefits The relative efficacy of quintuple and sextuple buprenorphine dosing in abating withdrawal symptoms for 120 h was compared in opioid-dependent out patients . Fourteen subjects received buprenorphine in a double-blind , placebo-controlled , cross-over design . Daily sublingual maintenance doses were 4 mg/70 kg ( n=4 ) and 8 mg/70 kg ( n=10 ) . After a stabilization period of daily maintenance administration , subjects received quintuple ( 5x daily maintenance dose ) and sextuple ( 6x daily maintenance dose ) doses every 120 h. Measures of opioid agonist and withdrawal effects were assessed daily . Subjective ratings of withdrawal were significantly greater than baseline ratings beyond 96-h post dosing under both regimens . There was no evidence , however , that those subjective ratings of withdrawal differed between the two regimens . Thus , these data suggest that sextuple buprenorphine dosing , administered every 5 days , does not abate opioid-withdrawal beyond 96 hours The authors studied the efficacy of the community reinforcement approach ( CRA ) as compared to st and ard counseling in opiate-dependent patients on methadone maintenance . One hundred eighty subjects were r and omized to three treatment conditions : st and ard , CRA , and CRA with relapse prevention ( CRA/RP ) . Of these , 151 subjects were followed up 6 months after intake . Since few of the RP sessions had been concluded at the 6-month follow-up , the two CRA groups were combined for analyses . Weekly urinalysis drug screens and Addiction Severity Index ( ASI ) scores at intake and 6 months were compared . The combined CRA groups did significantly better than the st and ard group in the following areas : consecutive opiate-negative urinalysis ( 3 weeks ) , and the 6-month ASI drug composite score . These results support the benefit of adding CRA strategies to the treatment of patients who are opiate dependent and on methadone maintenance . Because of insufficient treatment exposure to RP at the 6-month follow-up , the additive effect of RP could not be adequately evaluated ; further follow-up will be required This study compared the safety and efficacy of sublingual buprenorphine tablets with oral methadone in a population of opioid-dependent individuals in a double-blind , r and omized , 6-week trial using a flexible dosing procedure . Fifty-eight patients seeking treatment for opioid dependence were recruited in three outpatient facilities and r and omly assigned to substitution with buprenorphine or methadone . The retention rate was significantly better in the methadone maintained group ( 90 vs. 56 % ; P<0.001 ) . Subjects completing the study in both the treatment groups had similar proportions of opioid positive urine sample s ( buprenorphine 62 % ; methadone 59 % ) and positive urine specimens , as well as mean heroin craving scores decreased significantly over time ( P=0.035 and P<0.001 ) . The proportion of cocaine-positive toxicology results did not differ between groups . At week six mean stabilization doses were 10.5 mg per day for the sublingual buprenorphine tablet , and 69.8 mg per day for methadone , respectively . Patient performance during maintenance was similar in both the groups . The high attrition rate in the buprenorphine group during the induction phase might reflect inadequate induction doses . Thus , buprenorphine is a viable alternative for methadone in short-term maintenance treatment for heroin dependence if treatment induction is done with adequate dosages OBJECTIVE The authors tested the efficacy of individual psychotherapy in the rehabilitation counseling of psychiatrically symptomatic opiate-dependent patients during methadone maintenance treatment in community programs . METHOD Volunteers in three community programs were r and omly assigned to 24 weeks of counseling plus supplemental drug counseling or to counseling plus supportive-expressive psychotherapy . Follow-ups were done 1 and 6 months after treatment ended . A total of 84 subjects were evaluated at both follow-up points . RESULTS During the study the patients receiving supportive-expressive psychotherapy and those receiving drug counseling had similar proportions of opiate-positive urine sample s , but the patients receiving supportive-expressive psychotherapy had fewer cocaine-positive urine sample s and required lower doses of methadone . One month after the extra therapy ended both groups had made significant gains , but there were no significant differences between groups . By 6-month follow-up many of the gains made by the drug counseling patients had diminished , whereas most of the gains made by the patients who received supportive-expressive psychotherapy remained or were still evident ; many significant differences emerged , all favoring supportive-expressive psychotherapy . CONCLUSIONS Psychotherapy can be delivered to psychiatrically impaired patients in community methadone programs . Additional counseling is associated with early benefits comparable to those from psychotherapy , but these gains are not sustained . The gains associated with psychotherapy persist and in some cases strengthen for at least 6 months after the end of therapy PURPOSE Buprenorphine is an alternative to methadone for the maintenance treatment of heroine dependence and may be effective on a thrice weekly basis . Our objective was to evaluate the effect of thrice weekly buprenorphine maintenance for the treatment of heroin dependence in a primary care clinic on retention in treatment and illicit opioid use . SUBJECTS AND METHODS Opioid-dependent patients were r and omly assigned to receive thrice weekly buprenorphine maintenance in a primary care clinic that was affiliated with a drug treatment program ( n = 23 ) or in a traditional drug treatment program ( n = 23 ) in a 12-week clinical trial . Primary outcomes were retention in treatment and urine toxicology for opioids ; secondary outcomes were opioid withdrawal symptoms and toxicology for cocaine . RESULTS Retention during the 12-week study was higher in the primary care setting ( 78 % , 18 of 23 ) than in the drug treatment setting ( 52 % , 12 of 23 ; P = 0.06 ) . Patients admitted to primary care had lower rates of opioid use based on overall urine toxicology ( 63 % versus 85 % , P < 0.01 ) and were more likely to achieve 3 or more consecutive weeks of abstinence ( 43 % versus 13 % , P = 0.02 ) . Cocaine use was similar in both setting s. CONCLUSIONS Buprenorphine maintenance is an effective treatment for heroin dependence in a primary care setting Objective . To examine whether the addition of counseling , medical care , and psychosocial services improves the efficacy of methadone hydrochloride therapy in the rehabilitation of opiate‐dependent patients . Design . R and om assignment to one of three treatment groups for a 6‐month clinical trial : ( 1 ) minimum methadone services (MMS)—methadone alone ( a minimum of 60 mg/d ) with no other services ; ( 2 ) st and ard methadone services (SMS)—same dose of methadone plus counseling ; or ( 3 ) enhanced methadone services (EMS)—same dose of methadone plus counseling and on‐site medical/psychiatric , employment , and family therapy . Setting . The methadone maintenance program of the Philadelphia ( Pa ) Veterans Affairs Medical Center . Subjects . Ninety‐two male intravenous opiate users in methadone maintenance treatment . Results . While methadone treatment alone ( MMS ) was associated with reductions in opiate use , 69 % of these subjects had to be “ protectively transferred ” from the trial because of unremitting use of opiates or cocaine , or medical/psychiatric emergencies . This was significantly different from the 41 % of SMS subjects and 19 % of EMS subjects who met the criteria . End‐of‐treatment data ( at 24 weeks ) showed minimal improvements among the 10 MMS patients who completed the trial . The SMS group showed significantly more and larger improvements than did the MMS group ; and the EMS group showed significantly better outcomes than did the SMS group . Minimum methadone services subjects who had been “ protectively transferred ” to st and ard care showed significant reductions in opiate and cocaine use within 4 weeks . Conclusions . Methadone alone ( even in substantial doses ) may only be effective for a minority of eligible patients . The addition of basic counseling was associated with major increases in efficacy ; and the addition of on‐site professional services was even more effective A three-centre , r and omised , double-blind study was design ed to compare the efficacy and safety of buprenorphine and methadone . This was the first European study to compare these agents and was based on a previous trial performed in the US . Opioid-dependent subjects were r and omised to receive either sublingual buprenorphine or oral methadone daily . Both objective and subjective measures of efficacy were monitored weekly , and safety parameters were regularly monitored over the entire six-week study . Urinalysis showed that the two treatments were similar with a slight increase in opioid-negative urines noted in both groups . The retention rate in the buprenorphine group was lower than in the methadone group , although it has been suggested that the buprenorphine dose may have been too low for some patients . None of the side effects noted were considered serious and all were attributable to chronic opioid dependence . Experience of two years substitution treatment in Fribourg suggests that initial induction onto buprenorphine allows for patients to be subgrouped before being given the most appropriate maintenance agent . Further investigation is required into the different dose-related effects of buprenorphine seen in particular subsets of addicts As a maintenance agent for opioid dependency , buprenorphine offers advantages such as a lower level of dependence and minimal withdrawal symptoms , due to its partial agonist properties at the µ-opioid receptor . Previous studies have shown 8 mg sublingual buprenorphine to be equivalent to 60 mg oral methadone in terms of retention rate and opioid-negative urine levels . In a 24-week , ongoing European study , 34 opioid-dependent subjects were assessed ; 16 receiving buprenorphine and 18 methadone . A free dosing schedule was used with no upper limit for methadone dosing but with a maximum buprenorphine dose of 8 mg . Screening prior to the study excluded subjects with polysubstance dependence , somatic disease and /or HIV infection . Primary outcome measures were abstinence from other drugs , for which subjects provided weekly urine sample s for analysis of opioids , cocaine and benzodiazepines , and retention in treatment . Patients in the buprenorphine group provided a greater proportion of negative urine sample s , in particular cocaine-negative sample s , compared with the methadone group , although this was not statistically significant . Retention in the buprenorphine group was significantly lower than in the methadone group , suggesting that the 8 mg buprenorphine limit may have biased the results in favour of methadone , and that this dose may have been too low for those subjects with high levels of dependence . However , buprenorphine is clearly effective in the more motivated subjects and further investigation in this subgroup is recommended |
13,895 | 26,944,912 | The results were robust to multiple sensitivity analyses .
When imatinib loses patent protection and its price declines , its use will be the cost-effective initial treatment strategy for CML-CP | BACKGROUND We analyzed the cost-effectiveness of treating incident chronic myeloid leukemia in chronic phase ( CML-CP ) with generic imatinib when it becomes available in United States in 2016 .
In the year following generic entry , imatinib 's price is expected to drop 70 % to 90 % .
We hypothesized that initiating treatment with generic imatinib in these patients and then switching to the other tyrosine-kinase inhibitors ( TKIs ) , dasatinib or nilotinib , because of intolerance or lack of effectiveness ( " imatinib-first " ) would be cost-effective compared with the current st and ard of care : " physicians ' choice " of initiating treatment with any one of the three TKIs . | Most patients with chronic myeloid leukemia ( CML ) treated with imatinib will relapse if treatment is withdrawn . We conducted a prospect i ve clinical trial of imatinib withdrawal in 40 chronic-phase CML patients who had sustained undetectable minimal residual disease ( UMRD ) by conventional quantitative polymerase chain reaction ( PCR ) on imatinib for at least 2 years . Patients stopped imatinib and were monitored frequently for molecular relapse . At 24 months , the actuarial estimate of stable treatment-free remission was 47.1 % . Most relapses occurred within 4 months of stopping imatinib , and no relapses beyond 27 months were seen . In the 21 patients treated with interferon before imatinib , a shorter duration of interferon treatment before imatinib was significantly associated with relapse risk , as was slower achievement of UMRD after switching to imatinib . Highly sensitive patient-specific BCR-ABL DNA PCR showed persistence of the original CML clone in all patients with stable UMRD , even several years after imatinib withdrawal . No patients with molecular relapse after discontinuation have progressed or developed BCR-ABL mutations ( median follow-up , 42 months ) . All patients who relapsed remained sensitive to imatinib re-treatment . These results confirm the safety and efficacy of a trial of imatinib withdrawal in stable UMRD with frequent , sensitive molecular monitoring and early rescue of molecular relapse We present long-term follow-up of a dasatinib phase 3 study of patients with imatinib-resistant/-intolerant chronic myeloid leukemia ( CML ) . In the CA180 - 034 study , 670 patients with imatinib-resistant/-intolerant CML in chronic phase ( CML-CP ) received dasatinib 100 mg once daily , 50 mg twice daily , 140 mg once daily , or 70 mg twice daily . At 6 years , 188 ( 28 % ) of 670 patients remained on study treatment . Estimated 6-year protocol -defined progression-free survival ( PFS ) rates were 49 % , 51 % , 40 % , and 47 % , respectively , and estimated 6-year overall survival ( OS ) rates were 71 % , 74 % , 77 % , and 70 % , respectively ( intent-to-treat population , including protocol -defined progression or death after discontinuation ) . Estimated 6-year rates of survival without transformation on study treatment were 76 % , 80 % , 83 % , and 74 % , respectively . Major molecular response was achieved in 43 % ( 100 mg once daily ) and 40 % ( all other arms ) of patients by 6 years . Molecular and cytogenetic responses at 3 and 6 months were highly predictive of PFS and OS . Notably , estimated 6-year PFS rates based on ≤1 % , > 1 % to 10 % , and > 10 % BCR-ABL transcripts at 3 months were 68 % , 58 % , and 26 % , respectively . Most adverse events occurred by 2 years . Imatinib-resistant/-intolerant patients with CML-CP can experience long-term benefit with dasatinib therapy , particularly if achieving BCR-ABL ≤10 % at 3 months . This study was registered at Clinical Trials.gov : NCT00123474 Imatinib mesylate ( imatinib ) has been shown to be highly efficacious in the treatment of chronic myeloid leukemia ( CML ) . Continuous and adequate dosing is essential for optimal outcomes and with imatinib treatment possibly being lifelong , patient adherence is critical . The ADAGIO ( Adherence Assessment with Glivec : Indicators and Outcomes ) study aim ed to assess prospect ively over a 90-day period the prevalence of imatinib nonadherence in patients with CML ; to develop a multivariate canonical correlation model of how various determinants may be associated with various measures of nonadherence ; and to examine whether treatment response is associated with adherence levels . A total of 202 patients were recruited from 34 centers in Belgium , of whom 169 were evaluable . One-third of patients were considered to be nonadherent . Only 14.2 % of patients were perfectly adherent with 100 % of prescribed imatinib taken . On average , patients with suboptimal response had significantly higher mean percentages of imatinib not taken ( 23.2 % , st and ard deviation [ SD ] = 23.8 ) than did those with optimal response ( 7.3 % , SD = 19.3 , P = .005 ; percentages calculated as proportions x 100 ) . Nonadherence is more prevalent than patients , physicians , and family members believe it is , and therefore should be assessed routinely . It is associated with poorer response to imatinib . Several determinants may serve as alert signals , many of which are clinical ly modifiable We developed a module of the MD And erson Symptom Inventory ( MDASI ) for patients with chronic myeloid leukemia ( CML ) . To develop the MDASI-CML , we identified CML-specific symptoms from qualitative interviews with 35 patients . A list of c and i date symptoms was reduced by a panel of patients , caregivers , and clinicians to the 13 core MDASI symptom items and 6 CML-specific items ; these items were subsequently administered to 30 patients . Cognitive debriefing confirmed that the items were clear , relevant , and easy to use . One additional CML-specific symptom item was added , for a total of 7 . The refined MDASI-CML was administered to 152 patients once every 2 weeks for 1 year . The content , concurrent , known-group , and construct validity of the MDASI-CML were evaluated . The internal consistency and test-retest reliabilities of the module were adequate . Longitudinal analysis showed relatively stable symptom severity scores over time . The most severe symptoms were fatigue , drowsiness , disturbed sleep , muscle soreness and cramping , and trouble remembering things . Approximately one-third of the patients who completed the MDASI-CML reported persistent moderate-to-severe symptoms . The MDASI-CML is a valid and reliable symptom assessment instrument that can be used in clinical studies of symptom status in patients with CML This analysis explores the impact of early cytogenetic and molecular responses on the outcomes of patients with chronic myeloid leukemia in chronic phase ( CML-CP ) in the phase 3 DASatinib versus Imatinib Study In treatment-Naive CML patients trial with a minimum follow-up of 3 years . Patients with newly diagnosed CML-CP were r and omized to receive 100 mg dasatinib ( n = 259 ) or 400 mg imatinib ( n = 260 ) once daily . The retrospective l and mark analysis included patients evaluable at the relevant time point ( 3 , 6 , or 12 months ) . Median time to complete cytogenetic response was 3 vs 6 months with dasatinib vs imatinib . At 3 and 6 months , the proportion of patients with BCR-ABL transcript levels ≤10 % was higher in the dasatinib arm . Deeper responses at 3 , 6 , and 12 months were observed in a higher proportion of patients on dasatinib therapy and were associated with better 3-year progression-free survival and overall survival in both arms . First-line dasatinib result ed in faster and deeper responses compared with imatinib . The achievement of an early molecular response was predictive of improved progression-free survival and overall survival , supporting new milestones for optimal response in patients with early CML-CP treated with tyrosine kinase inhibitors . This study was registered at www . clinical trials.gov as NCT00481247 BACKGROUND Imatinib , a selective inhibitor of the BCR-ABL tyrosine kinase , produces high response rates in patients with chronic-phase chronic myeloid leukemia ( CML ) who have had no response to interferon alfa . We compared the efficacy of imatinib with that of interferon alfa combined with low-dose cytarabine in newly diagnosed chronic-phase CML . METHODS We r and omly assigned 1106 patients to receive imatinib ( 553 patients ) or interferon alfa plus low-dose cytarabine ( 553 patients ) . Crossover to the alternative group was allowed if stringent criteria defining treatment failure or intolerance were met . Patients were evaluated for hematologic and cytogenetic responses , toxic effects , and rates of progression . RESULTS After a median follow-up of 19 months , the estimated rate of a major cytogenetic response ( 0 to 35 percent of cells in metaphase positive for the Philadelphia chromosome ) at 18 months was 87.1 percent ( 95 percent confidence interval , 84.1 to 90.0 ) in the imatinib group and 34.7 percent ( 95 percent confidence interval , 29.3 to 40.0 ) in the group given interferon alfa plus cytarabine ( P<0.001 ) . The estimated rates of complete cytogenetic response were 76.2 percent ( 95 percent confidence interval , 72.5 to 79.9 ) and 14.5 percent ( 95 percent confidence interval , 10.5 to 18.5 ) , respectively ( P<0.001 ) . At 18 months , the estimated rate of freedom from progression to accelerated-phase or blast-crisis CML was 96.7 percent in the imatinib group and 91.5 percent in the combination-therapy group ( P<0.001 ) . Imatinib was better tolerated than combination therapy . CONCLUSIONS In terms of hematologic and cytogenetic responses , tolerability , and the likelihood of progression to accelerated-phase or blast-crisis CML , imatinib was superior to interferon alfa plus low-dose cytarabine as first-line therapy in newly diagnosed chronic-phase CML BACKGROUND In a r and omized trial , 1106 patients with chronic myeloid leukemia ( CML ) in chronic phase were assigned to imatinib or interferon alfa plus cytarabine as initial therapy . We measured levels of BCR-ABL transcripts in the blood of all patients in this trial who had a complete cytogenetic remission . METHODS Levels of BCR-ABL transcripts were measured by a quantitative real-time polymerase-chain-reaction assay . Results were expressed relative to the median level of BCR-ABL transcripts in the blood of 30 patients with untreated CML in chronic phase . RESULTS In patients who had a complete cytogenetic remission , levels of BCR-ABL transcripts after 12 months of treatment had fallen by at least 3 log in 57 percent of those in the imatinib group and 24 percent of those in the group given interferon plus cytarabine ( P=0.003 ) . On the basis of the rates of complete cytogenetic remission of 68 percent in the imatinib group and 7 percent in the group given interferon plus cytarabine at 12 months , an estimated 39 percent of all patients treated with imatinib but only 2 percent of all those given interferon plus cytarabine had a reduction in BCR-ABL transcript levels of at least 3 log ( P<0.001 ) . For patients who had a complete cytogenetic remission and a reduction in transcript levels of at least 3 log at 12 months , the probability of remaining progression-free was 100 percent at 24 months , as compared with 95 percent for such patients with a reduction of less than 3 log and 85 percent for patients who were not in complete cytogenetic remission at 12 months ( P<0.001 ) . CONCLUSIONS The proportion of patients with CML who had a reduction in BCR-ABL transcript levels of at least 3 log by 12 months of therapy was far greater with imatinib treatment than with treatment with interferon plus cytarabine . Patients in the imatinib group with this degree of molecular response had a negligible risk of disease progression during the subsequent 12 months BACKGROUND Nilotinib has been shown to be a more potent inhibitor of BCR-ABL than imatinib . We evaluated the efficacy and safety of nilotinib , as compared with imatinib , in patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia ( CML ) in the chronic phase . METHODS In this phase 3 , r and omized , open-label , multicenter study , we assigned 846 patients with chronic-phase Philadelphia chromosome-positive CML in a 1:1:1 ratio to receive nilotinib ( at a dose of either 300 mg or 400 mg twice daily ) or imatinib ( at a dose of 400 mg once daily ) . The primary end point was the rate of major molecular response at 12 months . RESULTS At 12 months , the rates of major molecular response for nilotinib ( 44 % for the 300-mg dose and 43 % for the 400-mg dose ) were nearly twice that for imatinib ( 22 % ) ( P<0.001 for both comparisons ) . The rates of complete cytogenetic response by 12 months were significantly higher for nilotinib ( 80 % for the 300-mg dose and 78 % for the 400-mg dose ) than for imatinib ( 65 % ) ( P<0.001 for both comparisons ) . Patients receiving either the 300-mg dose or the 400-mg dose of nilotinib twice daily had a significant improvement in the time to progression to the accelerated phase or blast crisis , as compared with those receiving imatinib ( P=0.01 and P=0.004 , respectively ) . No patient with progression to the accelerated phase or blast crisis had a major molecular response . Gastrointestinal and fluid-retention events were more frequent among patients receiving imatinib , whereas dermatologic events and headache were more frequent in those receiving nilotinib . Discontinuations due to aminotransferase and bilirubin elevations were low in all three study groups . CONCLUSIONS Nilotinib at a dose of either 300 mg or 400 mg twice daily was superior to imatinib in patients with newly diagnosed chronic-phase Philadelphia chromosome-positive CML . ( Clinical Trials.gov number , NCT00471497 . BACKGROUND The cause of chronic myeloid leukemia ( CML ) is a constitutively active BCR-ABL tyrosine kinase . Imatinib inhibits this kinase , and in a short-term study was superior to interferon alfa plus cytarabine for newly diagnosed CML in the chronic phase . For 5 years , we followed patients with CML who received imatinib as initial therapy . METHODS We r and omly assigned 553 patients to receive imatinib and 553 to receive interferon alfa plus cytarabine and then evaluated them for overall and event-free survival ; progression to accelerated-phase CML or blast crisis ; hematologic , cytogenetic , and molecular responses ; and adverse events . RESULTS The median follow-up was 60 months . Kaplan-Meier estimates of cumulative best rates of complete cytogenetic response among patients receiving imatinib were 69 % by 12 months and 87 % by 60 months . An estimated 7 % of patients progressed to accelerated-phase CML or blast crisis , and the estimated overall survival of patients who received imatinib as initial therapy was 89 % at 60 months . Patients who had a complete cytogenetic response or in whom levels of BCR-ABL transcripts had fallen by at least 3 log had a significantly lower risk of disease progression than did patients without a complete cytogenetic response ( P<0.001 ) . Grade 3 or 4 adverse events diminished over time , and there was no clinical ly significant change in the profile of adverse events . CONCLUSIONS After 5 years of follow-up , continuous treatment of chronic-phase CML with imatinib as initial therapy was found to induce durable responses in a high proportion of patients . ( Clinical Trials.gov number , NCT00006343 [ Clinical Trials.gov ] . This study examines the prognostic significance of early molecular response using an exp and ed data set in chronic myeloid leukemia patients enrolled in the International R and omized Study of Interferon and STI571 ( IRIS ) . Serial molecular studies demonstrate decreases in BCR-ABL transcripts over time . Analyses of event-free survival ( EFS ) and time to progression to accelerated phase/blast crisis ( AP/BC ) at 7 years were based on molecular responses using the international scale ( IS ) at 6- , 12- , and 18-month l and marks . Patients with BCR-ABL transcripts > 10 % at 6 months and > 1 % at 12 months had inferior EFS and higher rate of progression to AP/BC compared with all other molecular response groups . Conversely , patients who achieved major molecular response [ MMR : BCR-ABL ( IS ) ≤ 0.1 % ] by 18 months enjoyed remarkably durable responses , with no progression to AP/BC and 95 % EFS at 7 years . The probability of loss of complete cytogenetic response by 7 years was only 3 % for patients in MMR at 18 months versus 26 % for patients with complete cytogenetic response but not MMR ( P < .001 ) . This study shows a strong association between the degree to which BCR-ABL transcript numbers are reduced by therapy and long-term clinical outcome , supporting the use of time-dependent molecular measures to determine optimal response to therapy . This study is registered at www . clinical trials.gov as NCT00006343 BACKGROUND Imatinib treatment significantly improves survival in patients with chronic myeloid leukaemia ( CML ) , but little is known about whether treatment can safely be discontinued in the long term . We aim ed to assess whether imatinib can be discontinued without occurrence of molecular relapse in patients in complete molecular remission ( CMR ) while on imatinib . METHODS In our prospect i ve , multicentre , non-r and omised Stop Imatinib ( STIM ) study , imatinib treatment ( of > 2 years duration ) was discontinued in patients with CML who were aged 18 years and older and in CMR ( > 5-log reduction in BCR-ABL and ABL levels and undetectable transcripts on quantitative RT-PCR ) . Patients who had undergone immunomodulatory treatment ( apart from interferon α ) , treatment for other malignancies , or allogeneic haemopoietic stem-cell transplantation were not included . Patients were enrolled at 19 participating institutions in France . In this interim analysis , rate of relapse was assessed by use of RT-PCR for patients with at least 12 months of follow-up . Imatinib was reintroduced in patients who had molecular relapse . This study is registered with Clinical Trials.gov , number NCT00478985 . FINDINGS 100 patients were enrolled between July 9 , 2007 , and Dec 17 , 2009 . Median follow-up was 17 months ( range 1 - 30 ) , and 69 patients had at least 12 months follow-up ( median 24 months , range 13 - 30 ) . 42 ( 61 % ) of these 69 patients relapsed ( 40 before 6 months , one patient at month 7 , and one at month 19 ) . At 12 months , the probability of persistent CMR for these 69 patients was 41 % ( 95 % CI 29 - 52 ) . All patients who relapsed responded to re introduction of imatinib : 16 of the 42 patients who relapsed showed decreases in their BCR-ABL levels , and 26 achieved CMR that was sustained after imatinib rechallenge . INTERPRETATION Imatinib can be safely discontinued in patients with a CMR of at least 2 years duration . Imatinib discontinuation in this setting yields promising results for molecular relapse-free survival , raising the possibility that , at least in some patients , CML might be cured with tyrosine kinase inhibitors |
13,896 | 28,681,500 | There was no apparent impact on other intrapartum interventions , maternal or neonatal complications , such as admission to special care nursery ( average RR 0.97 , 95 % CI 0.76 to 1.25 ; 7 trials , 8897 women ; low- quality evidence ) , and exclusive or any breastfeeding at any time point ( average RR 1.05 , 95 % CI 0.96 to 1.16 ; 4 trials , 5584 women ; low- quality evidence ) .Subgroup analyses suggested that continuous support was most effective at reducing caesarean birth , when the provider was present in a doula role , and in setting s in which epidural analgesia was not routinely available .
Continuous labour support in setting s where women were not permitted to have companions of their choosing with them in labour , was associated with greater likelihood of spontaneous vaginal birth and lower likelihood of a caesarean birth .
Subgroup analysis of trials conducted in high-income compared with trials in middle-income countries suggests that continuous labour support offers similar benefits to women and babies for most outcomes , with the exception of caesarean birth , where studies from middle-income countries showed a larger reduction in caesarean birth .
No conclusions could be drawn about low-income setting s , electronic fetal monitoring , the timing of onset of continuous support or model of support .
Continuous support during labour may improve outcomes for women and infants , including increased spontaneous vaginal birth , shorter duration of labour , and decreased caesarean birth , instrumental vaginal birth , use of any analgesia , use of regional analgesia , low five-minute Apgar score and negative feelings about childbirth experiences .
We found no evidence of harms of continuous labour support .
Subgroup analyses should be interpreted with caution , and considered as exploratory and hypothesis-generating , but evidence suggests continuous support with certain provider characteristics , in setting s where epidural analgesia was not routinely available , in setting s where women were not permitted to have companions of their choosing in labour , and in middle-income country setting s , may have a favourable impact on outcomes such as caesarean birth . | BACKGROUND Historically , women have generally been attended and supported by other women during labour .
However , in hospitals worldwide , continuous support during labour has often become the exception rather than the routine .
OBJECTIVES The primary objective was to assess the effects , on women and their babies , of continuous , one-to-one intrapartum support compared with usual care , in any setting .
Secondary objectives were to determine whether the effects of continuous support are influenced by:1 .
Routine practice s and policies in the birth environment that may affect a woman 's autonomy , freedom of movement and ability to cope with labour , including : policies about the presence of support people of the woman 's own choosing ; epidural analgesia ; and continuous electronic fetal monitoring.2 .
The provider 's relationship to the woman and to the facility : staff member of the facility ( and thus has additional loyalties or responsibilities ) ; not a staff member and not part of the woman 's social network ( present solely for the purpose of providing continuous support , e.g. a doula ) ; or a person chosen by the woman from family members and friends;3 .
Timing of onset ( early or later in labour);4 . | BACKGROUND Data collected on more than 12,000 women in 15 r and omized controlled trials provide robust evidence of the beneficial effects of doula support on medical outcomes to childbirth . The objective of this paper was to examine the association between doula support and maternal perceptions of the infant , self , and support from others at 6 to 8 weeks postpartum . The doula was a minimally trained close female relative or friend . METHODS Six hundred low-risk , nulliparous women were enrolled in the original clinical trial and r and omized to doula support ( n = 300 ) or st and ard care ( n = 300 ) . The mother-to-be and her doula attended two 2-hour classes about providing nonmedical , continuous support to laboring women . For the secondary study , presented here , research participants ( N = 494 ) were interviewed by telephone using a 42-item question naire . RESULTS Overall , when doula-supported mothers ( n = 229 ) were compared with mothers who received st and ard care ( n = 265 ) , they were more likely to report positive prenatal expectations about childbirth and positive perceptions of their infants , support from others , and self-worth . Doula-supported mothers were also most likely to have breastfed and to have been very satisfied with the care they received at the hospital . CONCLUSIONS Labor support by a minimally trained female friend or relative , selected by the mother-to-be , enhances the postpartum well-being of nulliparous mothers and their infants , and is a low-cost alternative to professional doulas Background To evaluate the effectiveness and safety of the support given to women by a companion of their choice during labor and delivery . Methods A total of 212 primiparous women were enrolled in a r and omized controlled clinical trial carried out between February 2004 and March 2005 . One hundred and five women were allocated to the group in which support was permitted and 107 to the group in which there was no support . Variables regarding patient satisfaction and events related to obstetrical care , neonatal results and breastfeeding were evaluated . Student 's t-test or Wilcoxon 's test , chi-square or Fisher 's exact test , risk ratios , and their respective 95 % confidence intervals were used in the statistical analysis . Results Overall , the women in the support group were more satisfied with labor ( median 88.0 versus 76.0 , p < 0.0001 ) and delivery ( median 91.4 versus 77.1 , p < 0.0001 ) . During labor , patient satisfaction was associated with the presence of a companion ( RR 8.06 ; 95%CI : 4.84 – 13.43 ) , with care received ( RR 1.11 ; 95%CI : 1.01 – 1.22 ) and with medical guidance ( RR 1.14 95%CI : 1.01 – 1.28 ) . During delivery , satisfaction was associated with having a companion ( RR 5.57 , 95%CI : 3.70 – 8.38 ) , with care received ( RR 1.11 95%CI : 1.01 – 1.22 ) and with vaginal delivery ( RR 1.33 95%CI:1.02 – 1.74 ) . The only factor that was significantly lower in the support group was the occurrence of meconium-stained amniotic fluid ( RR 0.51 ; 95%CI : 0.28 – 0.94 ) . There was no statistically significant difference between the two groups with respect to any of the other variables . Conclusion The presence of a companion of the woman 's choice had a positive influence on her satisfaction with the birth process and did not interfere with other events and interventions , with neonatal outcome or breastfeeding Abstract Background Most women delivering in South African State Maternity Hospitals do not have a childbirth companion ; in addition , the quality of care could be better , and at times women are treated inhumanely . We piloted a multi-faceted intervention to encourage uptake of childbirth companions in state hospitals , and hypothesised that lay carers would improve the behaviour of health professionals . Methods We conducted a pilot r and omised controlled trial of an intervention to promote childbirth companions in hospital deliveries . We promoted evidence -based information for maternity staff at 10 hospitals through access to the World Health Organization Reproductive Health Library ( RHL ) , computer hardware and training to all ten hospitals . We surveyed 200 women at each site , measuring companionship , and indicators of good obstetric practice and humanity of care . Five hospitals were then r and omly allocated to receive an educational intervention to promote childbirth companions , and we surveyed all hospitals again at eight months through a repeat survey of postnatal women . Changes in median values between intervention and control hospitals were examined . Results At baseline , the majority of hospitals did not allow a companion , or access to food or fluids . A third of women were given an episiotomy . Some women were shouted at ( 17.7 % , N = 2085 ) , and a few reported being slapped or struck ( 4.3 % , N = 2080 ) . Despite an initial positive response from staff to the childbirth companion intervention , we detected no difference between intervention and control hospitals in relation to whether a companion was allowed by nursing staff , good obstetric practice or humanity of care . Conclusion The quality and humanity of care in these state hospitals needs to improve . Introducing childbirth companions was more difficult than we anticipated , particularly in under-re source d health care systems with frequent staff changes . We were unable to determine whether the presence of a lay carer impacted on the humanity of care provided by health professionals . Trial registration : Current Controlled Trials IS RCT The purpose of this stratified r and omized trial was to determine the physical and psychological effects of continuous , one-to-one professional support on childbirth outcomes . Data were gathered during prenatal and postpartum interviews with , and from the medical records of , 103 low-risk women . All subjects had attended one of two types of prenatal education programs , were accompanied by husb and s or partners during labor , and had vaginal deliveries . Subjects in the experimental group were less likely to have medication for pain relief and less likely to have episiotomies . Three variables were found to predict perceived control during childbirth -- expectations of control , the presence of a continuous professional caregiver , and pain medication usage . The results demonstrate the importance of the traditional nursing support role during childbirth OBJECTIVES : Despite recent efforts to increase breastfeeding , young African American mothers continue to breastfeed at low rates , and commonly introduce complementary foods earlier than recommended . This study examines the effects of a community doula home visiting intervention on infant feeding practice s among young mothers . METHODS : Low-income , African American mothers ( n = 248 ) under age 22 years participated in a r and omized trial of a community doula intervention . Intervention-group mothers received services from paraprofessional doulas : specialized home visitors trained as childbirth educators and lactation counselors . Doulas provided home visits from pregnancy through 3 months postpartum , and support during childbirth . Control-group mothers received usual prenatal care . Data were obtained from medical records and maternal interviews at birth and 4 months postpartum . RESULTS : Intent-to-treat analyses showed that doula-group mothers attempted breastfeeding at a higher rate than control-group mothers ( 64 % vs 50 % ; P = .02 ) and were more likely to breastfeed longer than 6 weeks ( 29 % vs 17 % ; P = .04 ) , although few mothers still breastfed at 4 months . The intervention also impacted mothers ’ cereal/solid food introduction ( P = .008 ) : fewer doula-group mothers introduced complementary foods before 6 weeks of age ( 6 % vs 18 % ) , while more waited until at least 4 months ( 21 % vs 13 % ) compared with control-group mothers . CONCLUSIONS : Community doulas may be effective in helping young mothers meet breastfeeding and healthy feeding guidelines . The intervention ’s success may lie in the relationship that develops between doula and mother based on shared cultural background and months of prenatal home visiting , and the doula ’s presence at the birth , where she supports early breastfeeding experiences Background Initiation of breastfeeding can be difficult in a busy maternity centre with inadequate manpower and social support . This study aims to explore the role of psychosocial support offered by companions on breastfeeding initiation among first-time mothers . Methods This is a secondary data analysis of a r and omised controlled trial conducted among women attending the antenatal clinic of the University College Hospital , Ibadan , Nigeria in 2007 . Those in the experimental group were asked to bring someone of their choice to the labour room to act as a companion ; the comparison group received st and ard care . The results of 209 HIV negative women who had vaginal births were analysed . The main outcome measure was time to initiation of breastfeeding after childbirth . Results Of the total , 94 had companions during labour while 115 did not have a companion . The median time to breastfeeding initiation was significantly shorter in those with companions compared to controls ( 16 vs. 54 minutes ; p < 0.01 ) . The cumulative survival analysis indicated that all in the treatment group had initiated breastfeeding by 26 minutes , while among the control group none had commenced at 30 minutes post-delivery with some as late as 12 hours . After Cox regression analysis was used to adjust for possible confounders , the outcome still showed a significant hazard ratio of 207.8 ( 95%CI 49.2 , 878.0 ; p < 0.01 ) among women who were supported by a companion . Conclusion Use of companions during labour is associated with earlier time to breastfeeding initiation among first-time mothers in Nigeria . Trial Registration Australian New Zeal and Clinical Trials Registry : ACTRN12609000994280 To establish the spontaneous miscarriage rate and compare it with the procedure related miscarriage rate for amniocentesis and chorionic villus sampling ( CVS ) by experienced operators OBJECTIVE To study the availability of humanized service and healthy birth and it 's effect on maternal and neonatal outcomes . METHODS A multicenteral prospect i ve r and omized control study was carried out in 9 maternity hospitals from Nov. 2000 to June 2001 . 6,758 laboring women were r and omly divided into study group and control group . In study group ( n = 3,437 ) , midwives accompany laboring women in whole course of birth until two hours after delivery . According WHO " Monitoring rules for normal birth " medical staff support the mothers in physiological , psychological and physical aspects . In control group ( n = 3,321 ) mothers receive traditional management . Midwives visit and check the mothers discoutinually . In two groups husb and s can company laboring women according women 's requirement . A question naire will be filled on the second day after birth . RESULTS In study group the spontaneous delivery rate was significant higher than that of control group ( 85.5 % vs 66.0 % , P < 0.01 ) . The cesarean section rate , postpartum hemorrhage rate , neonatal asphyxia rate and neonatal morbidity were marked lower in study group than those of control group ( P < 0.01 and P < 0.05 ) . CONCLUSIONS Appropriate mode of intrapartum care can decrease the cesarean section rate and promote the vaginal delivery , also it can improve the maternal and neonatal outcomes OBJECTIVE To compare labor outcomes in women accompanied by an additional support person ( doula group ) with outcomes in women who did not have this additional support person ( control group ) . DESIGN R and omized controlled trial . SETTING A women 's ambulatory care center at a tertiary perinatal care hospital in New Jersey . PATIENTS / PARTICIPANTS Six hundred nulliparous women carrying a singleton pregnancy who had a low-risk pregnancy at the time of enrollment and were able to identify a female friend or family member willing to act as their lay doula . INTERVENTIONS The doula group was taught traditional doula supportive techniques in two 2-hour sessions . MAIN OUTCOME MEASURES Length of labor , type of delivery , type and timing of analgesia/anesthesia , and Apgar scores . RESULTS Significantly shorter length of labor in the doula group , greater cervical dilation at the time of epidural anesthesia , and higher Apgar scores at both 1 and 5 minutes . Differences did not reach statistical significance in type of analgesia/anesthesia or cesarean delivery despite a trend toward lower cesarean delivery rates in the doula group . CONCLUSION Providing low-income pregnant women with the option to choose a female friend who has received lay doula training and will act as doula during labor , along with other family members , shortens the labor process We wanted to study the effect of extra emotional support in the form of a non-professional woman ( doula ) before and during delivery . About 200 primiparae were invited to participate in a prospect i ve study which intended to assess differences in delivery outcome between women with and without a doula . Fifty-four declined to participate , 55 had a delivery with doula and 46 were controls . Lower rate of emergency caesarean sections in the doula-group was noted . The parents as well as the staff , became to regard the doula as a valuable support during delivery Objective : Vasoconstriction during anxiety reduces fetal oxygenation and leads to hypoxia . Hypoxia in turn results in increase of the number of nucleated red blood cells ( NRBCs ) in the cord blood . The present study aim ed to assess the effect of decreasing maternal anxiety on fetal oxygenation and NRBCs count in the cord blood . Methods : . In this study , 150 women were r and omly divided into two intervention groups [ supportive care and acupressure in BL32 ( bladder ) acupoint ] and a control group ( hospital routine care ) . The infants ' cord blood was investigated regarding the number of NRBCs and the intensity of hypoxia after birth . Then , the data were entered into the SPSS statistical software ( v. 16 ) and analyzed using ANOVA , Chi-square test , and logistic regression analysis . Findings : The significant difference was found between the two groups regarding the number of NRBCs counted in the peripheral blood smear ( P<0.001 ) . Besides , a significant relationship was observed between the length of the first and second stages of labor and the number of NRBCs in the cord blood ( P=0.01 ) . Also , a significant association was observed between the type of delivery and the number of NRBCs in the cord blood in both intervention ( P<0.001 ) and control groups ( P=0.03 ) . Conclusion : Doula supportive care and acupressure at BL32 point reduced the length of labor stages as well as the anxiety level . Also , nucleated red blood cells were less in the 2 groups of intervention than in control group . Regarding the fact that nucleated red blood cells can not be the only factor for hypoxia predicting , for affirmation of this theory study with higher sample size and survey of mothers at high risk are needed Delivery is considered as one of the most painful experiences of women 's life . The present study aim ed to compare the effects of supportive care and acupressure on the pregnant women 's pain intensity and delivery outcome . In this experimental study , 150 pregnant women were r and omly divided into supportive care , acupressure , and control groups . The intensity of pain was measured using Visual Analogue Scale ( VAS ) . The supportive care group received both physical and emotional cares . In the acupressure group , on the other h and , BL32 acupoint was pressed during the contractions . Then , the data were analyzed using descriptive and inferential statistics . The results revealed significant difference among the three groups regarding the intensity of pain after the intervention ( P < 0.001 ) . Besides , the highest rate of natural vaginal delivery was observed in the supportive care group ( 94 % ) and the acupressure group ( 92 % ) , while the highest rate of cesarean delivery was related to the control group ( 40 % ) and the difference was statistically significant ( P < 0.001 ) . The results showed that maternal supportive care and acupressure during labor reduced the intensity of pain and improved the delivery outcomes . Therefore , these methods can be introduced to the medical team as effective strategies for decreasing delivery pain . This trial is registered with the Iranian Registry of Clinical Trial Code I RCT 2014011011706N5 Object To evaluate the effects of psychosocial support during labour , delivery and the immediate postpartum period provided by a female companion ( doula ) Various policies of management of prolonged labour have been proposed to prevent its two main consequences -- caesarean section and fetal distress . Two r and omised controlled trials were organised ; the first to assess the value of amniotomy with oxytocin compared to a more conservative approach . The second trial compared the effect of continuous professional support during labour with the intermittent presence of a member of staff . These were multicentre studies in several countries of Europe . Preliminary results of early amniotomy suggested no difference in the rate of operative delivery . Continuous professional support was associated with a significant reduction in operative deliveries BACKGROUND Supportive care during labor , the primary role of intrapartum nurses and midwives , provides comfort to prepartum women and helps facilitate a positive labor experience . It has been argued that supportive care during labor reduces fear and anxiety as well as the result ant side effects . However , evidence supporting this argument is insufficient . PURPOSE The aim of this study was to assess the effects of intrapartum supportive care on fear of delivery and on the key parameters of the labor process . METHODS This study used a single-blind r and omized controlled trial approach . R and omized block assignment was used to assign 72 participants to either the intervention group ( n = 36 ) or the control group ( n = 36 ) . Three women in the intervention group and six in the control group were later excluded from the study because they received emergency cesarean delivery . The intervention group received continuous supportive care , and the control group received routine hospital care . RESULTS No significant differences were identified between the two groups at baseline . The intervention group reported less fear of delivery during the active and transient phases of labor , higher perceived support and control during delivery , lower pain scores during the transient phase of labor , and a shorter delivery period than the control group ( p < .05 ) . However , no significant difference in the use of oxytocin during delivery between the two groups was reported . CONCLUSIONS / IMPLICATION S FOR PRACTICE The results of this evidence -based study suggest that continuous support during labor has clinical ly meaningful benefits for women and that all women should receive this support throughout their labor and delivery process BACKGROUND Previous r and omized controlled studies in several different setting s demonstrated the positive effects of continuous labor support by an experienced woman ( doula ) for low-income women laboring without the support of family members . The objective of this r and omized controlled trial was to examine the perinatal effects of doula support for nulliparous middle-income women accompanied by a male partner during labor and delivery . METHODS Nulliparous women in the third trimester of an uncomplicated pregnancy were enrolled at childbirth education classes in Clevel and , Ohio , from 1988 through 1992 . Of the 686 prenatal women recruited , 420 met enrollment criteria and completed the intervention . For the 224 women r and omly assigned to the experimental group , a doula arrived shortly after hospital admission and remained throughout labor and delivery . Doula support included close physical proximity , touch , and eye contact with the laboring woman , and teaching , reassurance , and encouragement of the woman and her male partner . RESULTS The doula group had a significantly lower cesarean delivery rate than the control group ( 13.4 % vs 25.0 % , p = 0.002 ) , and fewer women in the doula group received epidural analgesia ( 64.7 % vs 76.0 % , p = 0.008 ) . Among women with induced labor , those supported by a doula had a lower rate of cesarean delivery than those in the control group ( 12.5 % vs 58.8 % , p = 0.007 ) . On question naires the day after delivery , 100 percent of couples with doula support rated their experience with the doula positively . CONCLUSIONS For middle-class women laboring with the support of their male partner , the continuous presence of a doula during labor significantly decreased the likelihood of cesarean delivery and reduced the need for epidural analgesia . Women and their male partners were unequivocal in their positive opinions about laboring with the support of a doula Objective — To measure the effects of supportive companionship on labour and various aspects of adaptation to parenthood , and thus by inference the adverse effects of a clinical ly orientated labour environment on these processes Abstract Objective : To compare the differences in practicing continuous primary nursing care ( CPNC ) versus task-centered nursing care ( TCNC ) with regard to patient satisfaction with nursing care and early postpartum health problems for hospitalized pregnant women . Design : All participants filled out the satisfaction with nursing care question naire , breastfeeding knowledge question naire , and early postpartum problem question naire . Setting : Participants in the CPNC group received continuous individualized primary nursing care and participants in the TCNC group received task-centered nursing care during their perinatal period . Participants : Using a r and omized controlled trial , 470 hospitalized pregnant women participated in the study with 230 pregnant women in the CPNC group and 240 in TCNC group . Data Analysis : Question naire data were collected , calculated , and statistically analyzed using independent t-tests or χ2 tests along with power analysis . Results : Participants in the CPNC group reported significantly higher overall satisfaction with nursing care ( t(468 ) = 5.936 , p < .001 ) , had more breastfeeding knowledge ( t(468 ) = 5.633 , p < .001 ) , and were more likely to breast feed six weeks after delivery ( χ2 ( 1 ) = 39.237 , p < .001 ) than those in the TCNC group . Participants in the CPNC group also showed a significantly lower occurrence of postpartum urinary retention ( Fisher exact test was used , p < .002 ) and breast discomfort ( χ2 ( 3 ) = 34.482 , p < .001 ) than those in the TCNC group . Conclusion : Practicing continuous primary nursing care was more effective than practicing traditional task-centered nursing care for hospitalized pregnant women in increasing satisfaction with nursing care , enhancing breastfeeding , and reducing early postpartum problems OBJECTIVE The presence of a supportive companion to women in labour has been found to reduce the duration of labour and the incidence of oxytocin augmentation . The mechanism which produces this improvement is unknown but work in animals suggests that environmental disturbance produces changes in endogenous oxytocin secretion . This study was carried out to assess maternal oxytocin secretion in relation to the presence of a supportive companion in labour . STUDY DESIGN A r and omised controlled trial involving allocation of unsupported women in the first stage of labour to a period of 1 h with a supportive companion or 1 h without . Sixteen women with uncomplicated singleton pregnancies who were in the active phase of the first stage of labour were studied . Maternal oxytocin levels were assayed by radioimmunoassay for 16 min ( eight specimens ) before and after the support or control period . RESULTS There are no differences between maternal oxytocin levels in the two groups of patients . There was no difference in either of the two groups between the oxytocin levels pre and post the support/control period . CONCLUSIONS One hour of birth support in the first stage of labour did not improve maternal oxytocin levels when compared to a control group Because continuous social support during labour is a component of care in many societies but inconsistent in our own , the clinical effect of support during labour on maternal and neonatal morbidity were studied . Social support was provided by female companions . Four hundred and sixty five healthy primigravidous women were enrolled using a r and omised design . Compared with 249 women undergoing labour alone 168 women who had supportive female companions throughout labour had significantly fewer perinatal complications ( p less than 0.001 ) , including caesarean sections ( 7 % v 17 % , p less than 0.01 ) and oxytocin augmentation ( 2 % v 13 % , p less than 0.001 ) , and fewer infants admitted to neonatal intensive care ( p less than 0.10 ) . Of the women who had an uncomplicated labour and delivery requiring no interventions , those with a companion had a significantly shorter duration of labour ( 7.7 hours v 15.5 hours , p less than 0.001 ) . This study suggests that constant human support may be of great benefit to women during labour BACKGROUND Health research ers and provider groups have recommended that women in labor should receive continuous professional support . The objective of our study was to compare the risks and benefits of one-to-one nurse labor support with usual intrapartum nursing care . METHODS A r and omized , controlled trial was conducted in a 637-bed university hospital in Montreal , Quebec , with 413 nulliparous women who were at more than 37 weeks ' gestation , carrying singletons , and in labor . Women with scheduled cesarean section , scheduled induction , breech presentation , presence of paid labor support , or cervical dilatation over 4 cm were excluded . One-to-one care consisted of the presence of a nurse during labor and birth who provided emotional support , physical comfort , and instruction for relaxation and coping techniques . Usual care consisted of care for two or three laboring women with various types of supportive activities . RESULTS A beneficial trend due to one-to-one nurse support was found with a 17 percent reduction in risk of oxytocin stimulation ( relative risk of experimental vs control = 0.83 ; 95 % confidence interval = 0.67 , 1.04 ) . No significant differences were found in overall labor duration s and overall rates of total cesarean section , cesarean section for cephalopelvic disproportion , epidural analgesia , admission to the neonatal intensive care unit , instrumental vaginal delivery , and perineal trauma . CONCLUSIONS The beneficial trend attributed to one-to-one nursing in reduction of oxytocin stimulation suggests that implementation of recommendations for continuous professional support by intrapartum nursing staff may be appropriate in North America OBJECTIVE To evaluate the efficacy of a close female relative providing emotional and physical support during active labor and birth . DESIGN R and omized , two-group controlled clinical trial . SETTING Regional teaching hospital in the eastern part of Thail and with 782 beds . PARTICIPANTS Primiparous women ( N = 120 ) whose gestational ages were ≥ 36 weeks and who had uncomplicated pregnancies . METHODS Participants were r and omly assigned to receive usual care and support from a chosen close female relative from admission until 2 hours after birth or usual care only . Within 24 hours of birth , labor outcomes ( length of labor & type of birth ) and levels of maternal satisfaction were assessed . RESULTS Those in the experimental group had a significantly shorter duration of active labor and were more satisfied with their childbirth experiences than those in the control group . Differences between groups with respect to incidence of spontaneous delivery were not found . CONCLUSIONS A close female relative was effective in providing supportive care during labor and delivery . The integration of this nursing intervention for women and their families at public hospitals in Thail and is supported BACKGROUND : Epidural analgesia reduces pain and anxiety during childbirth . In this r and omized controlled trial , we sought to determine whether partner presence during the initiation of epidural analgesia reduces stress of both the mother and her partner and their perception of maternal pain . METHODS : Healthy , nulliparous women who were accompanied by their partners and requested neuraxial analgesia were enrolled into the study . The study took place in the Labor and Delivery Unit of a large tertiary hospital in Israel . Upon request for epidural analgesia , both partners were assessed for baseline anxiety ( numerical rating scale , 0 to 10 ) , systolic blood pressure , heart rate , estimated contraction pain of parturient ( verbal rating scale for pain , 0 to 10 ) , and salivary amylase . After measurements , couples were r and omized into 1 of 2 groups : “ partner in ” and “ partner out . ” Immediately after epidural catheter insertion , anxiety , arterial blood pressure , heart rate , and salivary amylase were measured again in both partners . Both partners were asked to complete the State Anxiety Inventory question naire measuring current anxiety . The parturient was asked to rate the pain of epidural catheter insertion . The primary outcome measurement was parturient and partner anxiety as assessed by the numerical rating scale . RESULTS : Eighty-four couples were r and omized ( partner in 41 , partner out 42 , protocol violation 1 ) . At baseline there was no difference in self-reported anxiety of parturients between the partner-in and partner-out groups ( median interquartile range 7.5 [ 6.0 to 9.0 ] versus 7.0 [ 3.5 to 8.5 ] ; P = 0.26 , difference in medians = −1.0 ; 95 % confidence interval [ CI ] of difference −2.0 to 1.0 ) . After epidural catheter insertion , parturients in the partner-in group had a higher level of anxiety than those in the partner-out group ( 8.0 [ 7.0 to 10.0 ] versus 7.0 [ 5.0 to 9.0 ] ; P = 0.03 , difference in medians −1.0 ; 95 % CI of difference −2.0 to 0.0 ) . Pain scores during epidural catheter placement were higher in partner-in than in partner-out groups ( 7.0 [ 4.0 to 8.0 ] versus 4.0 [ 3.0 to 6.0 ] ; P = 0.004 , difference in medians = −2.0 ; 95 % CI of difference −3.0 to −1.0 ) . CONCLUSION : Partner presence during epidural catheter insertion for labor analgesia did not decrease anxiety levels . To the contrary , anxiety and pain of epidural catheter placement were greater if the partner remained in the room OBJECTIVE To compare the benefits of one-to-one nurse labor support with the benefits of usual intrapartum nursing care in women stimulated with oxytocin . DESIGN A secondary analysis of a r and omized controlled trial . SETTING A 637-bed university hospital . PARTICIPANTS One hundred nulliparous women 37 weeks or more gestation , carrying singletons , in labor with vertex presentation , stimulated with oxytocin , less than 5 cm dilated at baseline , and not scheduled for cesarean delivery or induction nor having paid labor support present . INTERVENTIONS One-to-one care consisted of the presence of a nurse during labor and birth who provided emotional support , physical comfort , and instruction on relaxation and coping techniques . Usual care consisted of care for 2 - 3 laboring women with supportive activities varying by nurse . MAIN OUTCOME MEASURE Cesarean delivery . RESULTS A beneficial trend because of one-to-one nurse support , with a 56 % reduction in risk of total cesarean deliveries [ RR of experimental vs. control = 0.44 ( 95 % confidence interval = 0.19 to 1.01 ) ] . CONCLUSION The beneficial trend in reducing cesarean deliveries attributed to one-to-one nursing in women stimulated with oxytocin suggests that continuous support by intrapartum nursing staff may benefit women stimulated with oxytocin during labor OBJECTIVE Postpartum depression is a common feature of childbearing and is the cause of considerable morbidity . We have explored the possibility that clinical ly oriented care during labor may contribute to its occurrence . STUDY DESIGN Of 189 nulliparous women laboring in a familiar community hospital , 92 were allocated by r and omized , sealed envelopes to receive additional companionship from one of three volunteer labor companions recruited from the community . RESULTS The group receiving support attained higher self-esteem scores and lower postpartum depression and anxiety ratings 6 weeks after delivery . CONCLUSION In the clinical labor environment companionship modifies factors that contribute to the development of postnatal depression . We emphasize the importance of paying attention to the psychosocial environment in which labor takes place , to facilitate adaptation to parenthood The continuous presence of a supportive companion ( doula ) during labor and delivery in two studies in Guatemala shortened labor and reduced the need for cesarean section and other interventions . In a US hospital with modern obstetric practice s , 412 healthy nulliparous women in labor were r and omly assigned to a supported group ( n = 212 ) that received the continuous support of a doula or an observed group ( n = 200 ) that was monitored by an inconspicuous observer . Two hundred four women were assigned to a control group after delivery . Continuous labor support significantly reduced the rate of cesarean section deliveries ( supported group , 8 % ; observed group , 13 % ; and control group , 18 % ) and forceps deliveries . Epidural anesthesia for spontaneous vaginal deliveries varied across the three groups ( supported group , 7.8 % ; observed group , 22.6 % ; and control group , 55.3 % ) . Oxytocin use , duration of labor , prolonged infant hospitalization , and maternal fever followed a similar pattern . The beneficial effects of labor support underscore the need for a review of current obstetric practice OBJECTIVE To evaluate whether providing doulas during hospital-based labor affects mode of delivery , epidural use , breast-feeding , and postpartum perceptions of the birth , self-esteem , and depression . METHODS This was a r and omized study of nullipara enrollees in a group-model health maintenance organization who delivered in one of three health maintenance organization-managed hospitals ; 149 had doulas , and 165 had usual care . Study data were obtained from the mothers ' medical charts , study intake forms , and phone interviews conducted 4 - 6 weeks postpartum . RESULTS Women who had doulas had significantly less epidural use ( 54.4 % versus 66.1 % , P < .05 ) than women in the usual-care group . They also were significantly ( P < .05 ) more likely to rate the birth experience as good ( 82.5 % versus 67.4 % ) , to feel they coped very well with labor ( 46.8 % versus 28.3 % ) , and to feel labor had a very positive effect on their feelings as women ( 58.0 % versus 43.7 % ) and perception of their bodies ' strength and performance ( 58.0 % versus 41.0 % ) . The two groups did not differ significantly in rates of cesarean , vaginal , forceps , or vacuum delivery , oxytocin administration ; or breast-feeding , nor did they differ on the postpartum depression or self-esteem measures . CONCLUSION For this population and setting , labor support from doulas had a desirable effect on epidural use and women 's perceptions of birth , but did not alter need for operative deliveries BACKGROUND This study was a r and omized controlled trial of primigravidas in Botswana to determine the effectiveness of the presence of a female relative as a labor companion on labor outcomes . METHODS One hundred and nine primigravidas in uncomplicated spontaneous labor were r and omly distributed into a control group who labored without family members present , and an experimental group who had a female relative with them during labor . RESULTS Significantly more mothers in the experimental group had a spontaneous vaginal delivery ( 91 % vs 71 % ) , less intrapartum analgesia ( 53 % vs 73 % ) , less oxytocin ( 13 % vs 30 % ) , fewer amniotomies to augment labor ( 30 % vs 54 % ) , fewer vacuum extraction s ( 4 % vs 16 % ) , and fewer cesarean sections ( 6 % vs 13 % ) than in the control group . These differences were all significant at p < 0.05 . Epidural analgesia was not used in the hospital at the time of the study . The only analgesics used were intramuscular pethidine or hyoscine N-butylbromide ( Buscopan ) . CONCLUSIONS The presence in labor of a female relative was shown to be associated with fewer interventions and a higher frequency of normal delivery compared with the outcomes of those without family member support . The presence of a female relative as a labor companion is a low-cost , preventative intervention that is consistent with the traditional cultural practice s in Botswana . In the light of this and previous studies , all women giving birth in a hospital should be offered the choice of a female relative as a companion to give support during labor We studied the effects of a supportive lay woman ( " doula " ) on the length of labor and on mother-infant interaction after delivery in healthy Guatemalan primigravid women . Initial assignment of mothers to the experimental ( doula ) or control group was r and om , but controls showed a higher rate ( P less than 0.001 ) of subsequent perinatal problems ( e.g. cesarean section and meconium staining ) . It was necessary to admit 103 mothers to the control group and 33 to the experimental group to obtain 20 in each group with uncomplicated deliveries . In the final sample , the length of time from admission to delivery was shorter in the experimental group ( 8.8 vs. 19.3 hours , P less than 0.001 ) . Mothers who had a doula present during labor were awake more after delivery ( P less than 0.02 ) and stroked ( P less than 0.001 ) , smiled at ( P less than 0.009 ) , and talked to ( P less than 0.002 ) their babies more than the control mothers . These observations suggest that there may be major perinatal benefits of constant human support during labor The birth of a child and adaptation to motherhood is generally accepted to be a stressful life event . During this time women may experience significant physiological , phycological and emotional changes in their lives Background and Objectives : Prolonged labor leads to increase of cesarean deliveries , reduction of fetal heart rate , and maternal as well as infantile complications . Therefore , many women tend to use pharmacological or non-pharmacological methods for reduction of labor length . The present study aim ed to compare the effects of maternal supportive care and acupressure ( at BL32 acupoint ) on labor length and infant 's Apgar score . Methods : In this clinical trial , 150 women with low-risk pregnancy were r and omly divided into supportive care , acupressure , and control groups each containing 50 subjects . The data were collected using a question naire including demographic and pregnancy characteristics . Then , the data were analyzed using Chi-square test and one-way ANOVA . Results : The mean length of the first and second stages of labor was respectively 157.0±29.5 and 58.9±25.8 minutes in the supportive care group , 161.7±37.3 and 56.1±31.4 minutes in the acupressure group , ad 281.0±79.8 and 128.4±44.9 minutes in the control group . The difference between the length of labor stages was significant in the three study groups ( P<0.001 ) . Moreover , the frequency of Apgar score≥8 in the first and 5th minutes was higher in the supportive care and acupressure groups compared to the control group , and the difference was statistically significant ( P<0.001 ) . Conclusion : Continuous support and acupressure could reduce the length of labor stages and increase the infants ’ Apgar scores . Therefore , these methods , as effective non-pharmacological strategies , can be introduced to the medical staff to improve the delivery outcomes Objective : To assess maternal satisfaction with childbirth and intrapartum pain relief in nulliparous women labouring at term This research was conducted in a public general hospital in Mexico City , Mexico . The objective was to evaluate efficacy of the support given by a doula during labor to reduce cesarean rate . From March 1997 to February 1998 , a group of 100 pregnant women were studied . These women were at term , engaged in an active phase of labor , exhibited 3 cm . or more cervical dilatation , were nuliparous , had no previous uterine incision , and possessed adequate pelvises . The group was r and omly divided into two subgroups comprising 50 women , each : The first subgroup had the support of a childbirth educator trained as a doula , while the second subgroup did not have doula support . Measurements were recorded on the duration of labor , the use of pitocin , and whether or not the birth was a vaginal birth or cesarean section . Characteristics and gestational age were similar in both groups . Results confirmed that support by doulas during labor was associated with a significant reduction in cesarean birth and pitocin administration . There was a trend toward shorter labors and less use of epidurals . The results of this study showed , as in other trials measuring the impact of a doula ’s presence during labor and birth , that doula support during labor is associated with positive outcomes that have physical , emotional , and economic implication OBJECTIVE The purpose of this guideline is to provide guidance for the intrapartum management of spontaneous labour , whether normal or abnormal , in term , healthy women , and to provide guidance in the management of first and second stage dystocia to increase the likelihood of a vaginal birth and optimize birth outcomes . EVIDENCE Published literature was retrieved through search es of PubMed and the Cochrane Library in October 2011 using appropriate , controlled vocabulary ( e.g. , labour pain ; labour , obstetric ; dystocia ) and key words ( e.g. , obstetric labor , perineal care , dysfunctional labor ) . When appropriate , results were restricted to systematic review s , r and omized control trials/controlled clinical trials , and observational studies . Results were limited to the last 10 years . Search es were up date d on a regular basis and incorporated in the guideline up to June 15 , 2015 . VALUES The quality of evidence in this document was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care ( Table 1 ) . SUMMARY STATEMENTS RECOMMENDATIONS OBJECTIVE To evaluate the effect of continuous support provided by midwives during labor on the duration of the different stages of labor and the rate of cesarean delivery . METHOD A r and omized trial of 100 eligible nulliparous women who had not received education classes on childbirth . In the intervention group ( n=50 ) , continuous support during labor was provided ; the control group ( n=50 ) did not receive continuous support . RESULTS The two groups did not differ by age , employment , educational level , gestational age , economic status , and neonatal weight . Mean duration of the active phase of labor ( 167.9+/-76.3 vs 247.7+/-101 min , P<0.001 ) , second stage of labor ( 34.9+/-25.4 vs 55.3+/-33.7 min , P=0.003 ) , and the number of cesarean deliveries ( 4 vs 12 , P=0.026 ) were significantly lower in the intervention group compared with the control group . The rates of oxytocin use and Apgar scores of less than 7 at 5 minutes were similar between the two groups . CONCLUSION Continuous support provided by midwives during labor may reduce the duration of labor and the number of cesarean deliveries ; this model of support should be available to all women One hundred three women who were r and omized to receive either routine nursing care ( controls ) or routine care plus one-to-one support by an experienced monitrice ( experimental ) were compared as to obstetric outcomes and their memories of types of support they had from nurse , monitrice , and mate . Women assigned a monitrice arrived at the hospital significantly further along in labor , and nearly twice as many had no medication during labor and delivery . Significantly fewer of these women used stirrups during delivery , and more had intact perineums . There was no difference between groups in use of forceps or cesarean sections . Length of labor was confounded by use of medications . Mothers in the experimental group remembered receiving more physical comfort measures , emotional support , and advocacy from monitrices compared to control mothers who received intrapartum care from nurses Background : Although the labour and delivery outcomes of epidural analgesia have been investigated extensively , the effects on breast‐feeding success are not clearly identified |
13,897 | 27,785,772 | Conclusions This review reveals method ological changes over time , but reporting weaknesses remain , particularly with respect to transparency of model reporting | Background Previous review s have evaluated economic analyses of lipid-lowering therapies using lipid levels as surrogate markers for cardiovascular disease .
However , drug approval and health technology assessment agencies have stressed that surrogates should only be used in the absence of clinical endpoints .
Objective The aim of this systematic review was to identify and summarise the method ologies , weaknesses and strengths of economic models based on atherosclerotic cardiovascular disease event rates . | BACKGROUND The recent recognition that coronary-artery stenting has improved the short- and long-term outcomes of patients treated with angioplasty has made it necessary to reevaluate the relative benefits of bypass surgery and percutaneous interventions in patients with multivessel disease . METHODS A total of 1205 patients were r and omly assigned to undergo stent implantation or bypass surgery when a cardiac surgeon and an interventional cardiologist agreed that the same extent of revascularization could be achieved by either technique . The primary clinical end point was freedom from major adverse cardiac and cerebrovascular events at one year . The costs of hospital re sources used were also determined . RESULTS At one year , there was no significant difference between the two groups in terms of the rates of death , stroke , or myocardial infa rct ion . Among patients who survived without a stroke or a myocardial infa rct ion , 16.8 percent of those in the stenting group underwent a second revascularization , as compared with 3.5 percent of those in the surgery group . The rate of event-free survival at one year was 73.8 percent among the patients who received stents and 87.8 percent among those who underwent bypass surgery ( P<0.001 by the log-rank test ) . The costs for the initial procedure were $ 4,212 less for patients assigned to stenting than for those assigned to bypass surgery , but this difference was reduced during follow-up because of the increased need for repeated revascularization ; after one year , the net difference in favor of stenting was estimated to be $ 2,973 per patient . CONCLUSION As measured one year after the procedure , coronary stenting for multivessel disease is less expensive than bypass surgery and offers the same degree of protection against death , stroke , and myocardial infa rct ion . However , stenting is associated with a greater need for repeated revascularization CONTEXT Percutaneous coronary intervention ( PCI ) is associated with excellent short-term improvements in ischemic symptoms , yet only three fifths of PCI patients at 5 years and one third of patients at 10 years remain free of major adverse cardiac events ( MACE ) . OBJECTIVE To determine whether treatment with fluvastatin reduces MACE in patients who have undergone PCI . DESIGN AND SETTING R and omized , double-blind , placebo-controlled trial conducted at 77 referral centers in Europe , Canada , and Brazil . PATIENTS A total of 1677 patients ( aged 18 - 80 years ) recruited between April 1996 and October 1998 with stable or unstable angina or silent ischemia following successful completion of their first PCI who had baseline total cholesterol levels between 135 and 270 mg/dL ( 3.5 - 7.0 mmol/L ) , with fasting triglyceride levels of less than 400 mg/dL ( 4.5 mmol/L ) . INTERVENTIONS Patients were r and omly assigned to receive treatment with fluvastatin , 80 mg/d ( n = 844 ) , or matching placebo ( n = 833 ) at hospital discharge for 3 to 4 years . MAIN OUTCOME MEASURE Survival time free of MACE , defined as cardiac death , nonfatal myocardial infa rct ion , or reintervention procedure , compared between the treatment and placebo groups . RESULTS Median time between PCI and first dose of study medication was 2.0 days , and median follow-up was 3.9 years . MACE-free survival time was significantly longer in the fluvastatin group ( P = .01 ) . One hundred eighty-one ( 21.4 % ) of 844 patients in the fluvastatin group and 222 ( 26.7 % ) of 833 patients in the placebo group had at least 1 MACE ( relative risk [ RR ] , 0.78 ; 95 % confidence interval [ CI ] , 0.64 - 0.95 ; P = .01 ) . This result was independent of baseline total cholesterol levels ( above [ RR , 0.76 ; 95 % CI , 0.56 - 1.04 ] vs below [ RR , 0.77 ; 95 % CI , 0.57 - 1.02 ] the median ) . In subgroup analysis , the risk of MACE was reduced in patients with diabetes ( n = 202 ; RR , 0.53 ; 95 % CI , 0.29 - 0.97 ; P = .04 ) and in those with multivessel disease ( n = 614 ; RR , 0.66 ; 95 % CI , 0.48 - 0.91 ; P = .01 ) who received fluvastatin compared with those who received placebo . There were no instances of creatine phosphokinase elevations 10 or more times the upper limit of normal or rhabdomyolysis in the fluvastatin group . CONCLUSION Fluvastatin treatment in patients with average cholesterol levels undergoing their first successful PCI significantly reduces the risk of major adverse cardiac events BACKGROUND The objective of this study was to assess the cost-effectiveness of pravastatin therapy in survivors of myocardial infa rct ion with average cholesterol levels . METHODS We performed a cost-effectiveness analysis based on actual clinical , cost , and health-related quality -of-life data from the Cholesterol and Recurrent Events ( CARE ) trial . Survival and recurrent coronary heart disease events were modeled from trial data in Markov models , with the use of different assumptions regarding the long-term benefit of therapy . RESULTS Pravastatin therapy increased quality -adjusted life expectancy at an incremental cost of $ 16,000 to $ 32,000 per quality -adjusted life-year gained . In subgroup analyses , the cost-effectiveness of pravastatin therapy was more favorable for patients > 60 years of age and for patients with pretreatment low-density lipoprotein cholesterol levels > 125 mg/dL. Results were sensitive to the cost of pravastatin and to assumptions about long-term survival benefits from pravastatin therapy . CONCLUSIONS The cost-effectiveness of pravastatin therapy in survivors of myocardial infa rct ion with average cholesterol levels compares favorably with other interventions OBJECTIVE To evaluate the incremental cost-effectiveness ratio ( ICER ) of switching to ezetimibe/simvastatin ( Eze/Simva ) compared with doubling the submaximal statin doses , in patients with acute coronary syndrome ( ACS ) events in the INFORCE study . METHODS Lifetime treatment costs and benefits were computed using a Markov model . Model inputs included each patient 's cardiovascular risk factor profile and actual lipid values at baseline and 12 weeks ( endpoint ) . Cardiovascular event and drug costs were discounted at 3.5 % . Age-specific utilities were based on UK literature values and non-coronary heart disease mortality rates on the Office of National Statistics data . In the INFORCE study , 384 patients taking statins at stable doses for ≥6 weeks before hospital admission were stratified by statin dose/potency ( low , medium , and high ) and then r and omized to doubling the statin dose or switching to Eze/Simva 10/40 mg for 12 weeks . RESULTS The Eze/Simva group ( n=195 ) had a higher mean baseline total cholesterol than the double-statin group ( n=189 ) . Analyses were adjusted for baseline characteristics . In the INFORCE study , Eze/Simva reduced low-density lipoprotein cholesterol ( LDL-C ) by ∼30 % ( vs. 4 % with doubling statin doses ) and significantly enhanced LDL-C goal attainment . In the cost-effectiveness analysis , Eze/Simva conferred 0.218 incremental discounted quality -adjusted life year ( QALY ) at a discounted incremental cost of £ 2524 , for an ICER of £ 11,571/QALY ( 95 % confidence interval=£8181-£18,600/QALY ) . The ICER was £ 13,552/QALY , £ 11,930/QALY , and £ 10,148/QALY in the low- , medium- , and high-potency strata , respectively . CONCLUSIONS Switching to Eze/Simva 10/40 mg is projected to be a cost-effective treatment ( vs. double-statin ) in UK patients with ACS The Beaver Dam Health Outcomes Study ( BDHOS ) is an ongoing longitudinal cohort study of health status and health-related quality of life for a r and om sample of adults ( age range at interview was 45 to 89 years ; mean = 64.1 , SD = 10.8 ) in a community population . In a face-to-face interview lasting approximately an hour , each participant responds to several batteries of questions . Included are a history of chronic medical conditions , current medi cations , and past surgeries ; the SF-36 ( a general health-status question naire ) ; the Quality of Well-being index ; self-rated health status on a five-point scale from " excellent " to " poor " ; and evaluation of current health using the method of time tradeoffs . The authors present results from 1,356 interviews on these four principal measures , reporting mean scores by sex , by age , and for persons reporting being affected by various medical conditions . They believe data from the BDHOS will provide research ers and policy makers a reference col lection of vital statistics for health-related quality of life . Additionally , the data provide a way to compare results from studies that utilize different indices from among the four principal measures of the BDHOS . Key words : health status ; quality of life ( health-related ) ; population study ; cohort study . ( Med Decis Making 1993;13:89 - 102 Drug therapy for hypercholesterolaemia has remained controversial mainly because of insufficient clinical trial evidence for improved survival . The present trial was design ed to evaluate the effect of cholesterol lowering with simvastatin on mortality and morbidity in patients with coronary heart disease ( CHD ) . 4444 patients with angina pectoris or previous myocardial infa rct ion and serum cholesterol 5.5 - 8.0 mmol/L on a lipid-lowering diet were r and omised to double-blind treatment with simvastatin or placebo . Over the 5.4 years median follow-up period , simvastatin produced mean changes in total cholesterol , low-density-lipoprotein cholesterol , and high-density-lipoprotein cholesterol of -25 % , -35 % , and + 8 % , respectively , with few adverse effects . 256 patients ( 12 % ) in the placebo group died , compared with 182 ( 8 % ) in the simvastatin group . The relative risk of death in the simvastatin group was 0.70 ( 95 % CI 0.58 - 0.85 , p = 0.0003 ) . The 6-year probabilities of survival in the placebo and simvastatin groups were 87.6 % and 91.3 % , respectively . There were 189 coronary deaths in the placebo group and 111 in the simvastatin group ( relative risk 0.58 , 95 % CI 0.46 - 0.73 ) , while noncardiovascular causes accounted for 49 and 46 deaths , respectively . 622 patients ( 28 % ) in the placebo group and 431 ( 19 % ) in the simvastatin group had one or more major coronary events . The relative risk was 0.66 ( 95 % CI 0.59 - 0.75 , p < 0.00001 ) , and the respective probabilities of escaping such events were 70.5 % and 79.6 % . This risk was also significantly reduced in subgroups consisting of women and patients of both sexes aged 60 or more . Other benefits of treatment included a 37 % reduction ( p < 0.00001 ) in the risk of undergoing myocardial revascularisation procedures . This study shows that long-term treatment with simvastatin is safe and improves survival in CHD patients Objective : To identify sociodemographic differences in the incidence of the subtypes of first ever stroke in a multiethnic population . Methods : A prospect i ve community stroke register ( 1995–8 ) was developed using multiple notification sources and pathological and clinical classifications of stroke . St and ardisation of rates was to European and World population s and adjusted for age , sex and socioeconomic status in multivariate analyses . A multiethnic population of 234 533 in south London , of whom 21 % are black was studied . Results : A total of 1254 cases were registered . The average age of stroke was 71.7 years with black patients being 11.3 years younger than white patients ( p<0.0001 ) . The incidence rate/1000 population was 1.33 ( crude ) ( 95 % CI 1.26 to 1.41 ) , 1.28 ( European adjusted ) ( 95 % CI 1.2 to 1.35 ) with a 2.18 ( 95 % CI 1.86 to 2.56 ) ( p<0.0001 ) age and sex adjusted incidence rate ratio in the black population . Radiological diagnosis was confirmatory in 1107 ( 88.3 % ) with 862 ( 68.7 % ) infa rct ion , 168 ( 13.4 % ) primary intracerebral haemorrhage , and 77 ( 6.2 % ) subarachnoid haemorrhage . Of the cerebral infa rct ion cases 189 ( 21.9 % ) were total anterior circulatory , 250 ( 29 % ) partial anterior , 141 ( 16.4 % ) posterior ( POCI ) and 282 ( 32.7 % ) lacunar infa rcts . The black group had a significantly higher incidence of all subtypes of stroke except for POCI and unclassified strokes . The incidence rate ratio ( IRR ) for men compared with women was 1.34 ( 95 % confidence interval ( 95 % CI ) 1.19 to 1.50 ; p<0.001 ) . The IRR for manual versus non-manual occupations in those aged 35–64 years was 1.64 ( 95%CI 1.22 to 2.23 ; p<0.0001 ) . There was a borderline significant increase in adjusted survival at 6 months in the black group 95 % ( CI 0.61 to 1.03 , p=0.078 ) with a hazard ratio of 0.79 after adjustment and stratification . Conclusions : Although the black population is at increased risk of stroke and most subtypes of stroke , this is not translated into significant differences in survival . Hence black/white differences in mortality are mainly driven by incidence of stroke . There are striking demographic inequalities in the risk of stroke in this multiethnic inner city population that need to be tackled through interagency working . Although the reasons for the increased risk in the black population are unclear , demographic factors such as socioeconomic status do seem to play a significant independent part For some patients with coronary artery disease , percutaneous transluminal coronary angioplasty ( PTCA ) is an alternative to coronary artery bypass grafting ( CABG ) . We report comparative health service costs of these interventions within the R and omised Intervention Treatment of Angina ( RITA ) trial . Medications were costed at published UK prices ; other re source use was costed with a set of unit costs estimated at two recruiting centres to the RITA trial , one in London and one outside . Over 2-year follow-up of 1011 patients , the estimated mean additional cost for those r and omised to CABG compared with PTCA was 1050 pounds ( 95 % CI 621 pounds-1479 pounds ) , with unit costs from the non-London centre , and 1823 pounds ( 1202 pounds-2444 pounds ) , with unit costs from the London centre . The initial average cost of treating a patient r and omised to PTCA is about 52 % of that of CABG , but after 2 years this increased to about 80 % because of the greater need for subsequent interventions . The balance of advantage between PTCA and CABG may change after several years : funding has been obtained to continue RITA follow-up for 10 years . However , on the basis of patients ' status at 2 years , the cost advantages of PTCA can not be ignored . Further research is necessary to assess whether the advantage of PTCA in terms of cost is translated into one of cost-effectiveness OBJECTIVE To determine the cost-effectiveness of lipid-lowering therapy in the secondary prevention of cardiovascular events in the Philippines . METHODS A cost-utility analysis was performed by using Markov modeling in the secondary prevention setting . The models incorporated efficacy of lipid-lowering therapy demonstrated in r and omized controlled trials and mortality rates obtained from local life tables . Average and incremental cost-effectiveness ratios were obtained for simvastatin , atorvastatin , pravastatin , and gemfibrozil . The costs of the following were included : medications , laboratory examinations , consultation and related expenses , and production losses . The costs were expressed in current or nominal prices as of the first quarter of 2010 ( Philippine peso ) . Utility was expressed in quality -adjusted life-years gained . Sensitivity analyses were performed by using variations in the cost centers , discount rates , starting age , and differences in utility weights for stroke . RESULTS In the analysis using the lower-priced generic counterparts , therapy using 40 mg simvastatin daily was the most cost-effective option compared with the other therapies , while pravastatin 40 mg daily was the most cost-effective alternative if the higher-priced innovator drugs were used . In all sensitivity analyses , gemfibrozil was strongly dominated by the statins . CONCLUSIONS In secondary prevention , simvastatin or pravastatin were the most cost-effective options compared with atorvastatin and gemfibrozil in the Philippines . Gemfibrozil was strongly dominated by the statins BACKGROUND Contemporary clinical trials commonly measure quality of life and medical costs to establish whether therapies are both effective and cost effective . Cost-effectiveness analysis , however , requires a measure of patient utility or preferences for various health states . Because utilities are not often measured directly , we sought to develop a method of translating st and ard quality -of-life scales into a patient utility measure . METHODS Five hundred fifty-three patients enrolled in the Bypass Angioplasty Revascularization Investigation Study of Economics and Quality of Life completed a battery of quality -of-life measures and a time trade-off utility assessment an average of 7.3 years after r and om assignment . RESULTS The mean time trade-off score was 8.54 ( SD = 2.53 ) out of a maximum of 10 ; median score was 9.95 . The distribution of scores was skewed , with 12 % of patients at the highest possible score of 10 . Patients with recurrent angina had significantly lower time trade-off scores than patients without angina ( mean 7.03 vs 8.70 , P < .05 ) . Time trade-off scores were moderately correlated with each quality -of-life measure ( Spearman coefficients 0.38 - 0.52 ) . Time trade-off scores could be predicted by combinations of 4 ( r2 = 0.29 ) , 5 ( r2 = 0.31 ) , or 6 ( r2 = 0.32 ) variables . CONCLUSIONS Time trade-off utility scores can be inferred from commonly used quality -of-life measures . Angina significantly reduces patient utility scores A prospect i ve study of acute cerebrovascular disease in a community of about 105,000 people is reported . The study protocol combined rapid clinical assessment of patients with accurate diagnosis of the pathological type of stroke by CT or necropsy , whether or not they were admitted to hospital . The study population was defined as those people who were registered with one of 50 collaborating general practitioners ( GPs ) . Referrals to the study were primarily from the GPs though , to ensure complete case ascertainment , hospital casualty and admission registers , death certificates and special data from the Oxford Record Linkage Study were also scrutinized . Six hundred and seventy five cases of clinical ly definite first-ever in a lifetime stroke were registered in four years yielding a crude annual incidence of 1.60/1,000 or 2.00/1,000 when adjusted to the 1981 population of Engl and and Wales . The age and sex specific incidence rates for first stroke showed a steep rise with age for both sexes . The odds of a male sustaining a first stroke were 26 % greater than those of a female . Ninety one per cent of patients were examined in a median time of four days after the event by a study neurologist and 88 % had cerebral CT or necropsy Method ological differences and variations in health care regulations among countries often preclude direct comparisons of cost-effectiveness studies . A projected risk model was applied , design ed to determine the economic value in the United States of pravastatin in the secondary prevention of coronary heart disease ( CHD ) , to Belgium using local health care costs . A Markov process was used to model the effectiveness of treatment for 3 years with pravastatin versus placebo in 1000 male CHD patients aged 60 years and clinical ly similar to those in the pravastatin limitation of atherosclerosis in the coronary arteries ( PLAC I ) and pravastatin , lipids and atherosclerosis in the carotid arteries ( PLAC II ) studies . The PLAC I and II trials have shown that pravastatin treatment for 3 years at a weighted mean dose of 36.64 mg daily significantly reduced the incidence of non-fatal myocardial infa rct ion in patients with CHD . Framingham data were used to project the risk of mortality 10 years post-myocardial infa rct ion . The incremental cost per life year gained ( LYG ) , after discounting costs and benefits by 5 % annually , in the setting of Belgian health care regulations , was Belgian francs ( BEF ) 720794 ( US$ 24359 ) for CHD patients with one additional risk factor ; BEF 526464 ( US$ 17792 ) for those with two additional risk factors ; and BEF 392765 ( US$ 13274 ) for those with three or more additional risk factors . The cost per LYG in Belgium appeared to be more sensitive to drug acquisition cost than to costs of medical interventions . The cost-effectiveness ratios of pravastatin monotherapy for 3 years in secondary prevention of CHD , obtained with the same projected risk model , are from 86 to 92 % higher in Belgium than in the United States , due to differences in medical patterns of practice and in intervention costs Abstract Objectives To measure the effectiveness and cost effectiveness of providing care in a chest pain observation unit compared with routine care for patients with acute , undifferentiated chest pain . Design Cluster r and omised controlled trial , with 442 days r and omised to the chest pain observation unit or routine care , and cost effectiveness analysis from a health service costing perspective . Setting The emergency department at the Northern General Hospital , Sheffield , United Kingdom . Participants 972 patients with acute , undifferentiated chest pain ( 479 attending on days when care was delivered in the chest pain observation unit , 493 on days of routine care ) followed up until six months after initial attendance . Main outcome measures The proportion of participants admitted to hospital , the proportion with acute coronary syndrome sent home inappropriately , major adverse cardiac events over six months , health utility , hospital reattendance and readmission , and costs per patient to the health service . Results Use of a chest pain observation unit reduced the proportion of patients admitted from 54 % to 37 % ( difference 17 % , odds ratio 0.50 , 95 % confidence interval 0.39 to 0.65 , P < 0.001 ) and the proportion discharged with acute coronary syndrome from 14 % to 6 % ( 8 % , −7 % to 23 % , P = 0.264 ) . Rates of cardiac event were unchanged . Care in the chest pain observation unit was associated with improved health utility during follow up ( 0.0137 quality adjusted life years gained , 95 % confidence interval 0.0030 to 0.0254 , P = 0.022 ) and a saving of £ 78 per patient ( −£56 to £ 210 , P = 0.252 ) . Conclusions Care in a chest pain observation unit can improve outcomes and may reduce costs to the health service . It seems to be more effective and more cost effective than routine care OBJECTIVE To measure the cost-effectiveness of cholesterol-lowering therapy with pravastatin in patients with established ischaemic heart disease and average baseline cholesterol levels . DESIGN Prospect i ve economic evaluation within a double-blind r and omised trial ( Long-Term Intervention with Pravastatin in Ischaemic Disease [ LIPID ] ) , in which patients with a history of unstable angina or previous myocardial infa rct ion were r and omised to receive 40 mg of pravastatin daily or matching placebo . PATIENTS AND SETTING 9014 patients aged 35 - 75 years from 85 centres in Australia and New Zeal and , recruited from June 1990 to December 1992 . MAIN OUTCOME MEASURES Cost per death averted , cost per life-year gained , and cost per quality -adjusted life-year gained , calculated from measures of hospitalisations , medication use , outpatient visits , and quality of life . RESULTS The LIPID trial showed a 22 % relative reduction in all-cause mortality ( P < 0.001 ) . Over a mean follow-up of 6 years , hospital admissions for coronary heart disease and coronary revascularisation were reduced by about 20 % . Over this period , pravastatin cost $ A4913 per patient , but reduced total hospitalisation costs by $ A1385 per patient and other long-term medication costs by $ A360 per patient . In a sub sample of patients , average quality of life was 0.98 ( where 0 = dead and 1 = normal good health ) ; the treatment groups were not significantly different . The absolute reduction in all-cause mortality was 3.0 % ( 95 % CI , 1.6%-4.4 % ) , and the incremental cost was $ 3246 per patient , result ing in a cost per life saved of $ 107 730 ( 95 % CI , $ 68 626-$209 881 ) within the study period . Extrapolating long-term survival from the placebo group , the undiscounted cost per life-year saved was $ 7695 ( and $ 10 938 with costs and life-years discounted at an annual rate of 5 % ) . CONCLUSIONS Pravastatin therapy for patients with a history of myocardial infa rct ion or unstable angina and average cholesterol levels reduces all-cause mortality and appears cost effective compared with accepted treatments in high-income countries Abstract Objective : To measure the health of a representative sample of the population of the United Kingdom by using the EuroQoL EQ-5D question naire . Design : Stratified r and om sample representative of the general population aged 18 and over and living in the community . Setting : United Kingdom . Subjects : 3395 people resident in the United Kingdom . Main outcome measures : Average values for mobility , self care , usual activities , pain or discomfort , and anxiety or depression . Results : One in three respondents reported problems with pain or discomfort . There were differences in the perception of health according to the respondent 's age , social class , education , housing tenure , economic position , and smoking behaviour . Conclusions : The EQ-5D question naire is a practical way of measuring the health of a population and of detecting differences in subgroups of the population . Key messages Measurement of health outcome requires the observation of states of health Patients ' involvement in recording and assessing their own state of health is a major element in the process of evaluating the impact of health care The EuroQoL EQ-5D question naire highlights variations in states of health which are consistent with previously published results High degrees of pain are reported in the general population . A category for pain is absent and thus undetected in the survey of disability by the Office of Population Censuses and OBJECTIVE To determine the cost-effectiveness of simvastatin in the secondary prevention of coronary artery disease ( CAD ) in Canada . DESIGN Cost-effectiveness model based on results from the Sc and inavian Simvastatin Survival Study ( 45 study ) and cost and re source utilization data from Canadian sources to simulate the economic impact of long-term simvastatin treatment ( 15 years ) . PATIENTS Subjects with mean age of 59.4 years at recruitment into 4S study . OUTCOME MEASURES Overall death rate and incidence of 5 major nonfatal events associated with CAD : myocardial infa rct ion , coronary artery bypass grafting , percutaneous transluminal coronary angioplasty , stroke and transient ischemic attack . Direct medical costs associated with CAD were assessed from the perspective of provincial ministries of health ( i.e. , costs borne by the ministries ) ; the impact of simvastatin treatment on these costs was determined . RESULTS The 4S study , with a median follow-up of 5.4 years , showed significantly reduced mortality and morbidity among the patients given simvastatin compared with the control subjects . Three premises were design ed to predict the consequences of simvastatin treatment of CAD in Canada over 15 years , 10 years beyond the end of the 4S study . The 2 most probable premises , which assumed that the clinical benefits of simvastatin would be cumulative for either the first 10 years or the full 15 years of the model , had incremental costs per year of life gained ( cost-effectiveness ratio ) of $ 9867 and $ 6108 respectively . CONCLUSION This model suggests that simvastatin provides a cost-effective approach to the long-term prevention of secondary CAD in Canada Clinical management of heterozygous familial hypercholesterolaemia is largely based on evidence from a small number of observational studies and extrapolation from the results of clinical trials of lipid-lowering in patients with polygenic hypercholesterolaemia The objectives of this study were ( i ) to determine the absolute and relative mortality of patients with treated heterozygous familial hypercholesterolaemia , ( ii ) to estimate the effect of changes in treatment efficacy on mortality trends over time , and ( iii ) to examine the implication s of these findings for patient management . A cohort of 605 men and 580 women aged 20 - 79 years with heterozyous familial hypercholesterolaemia were recruited from 21 out-patient lipid clinics in the UK . Patients were followed prospect ively from 1980 to 1995 for 8770 person-years . Absolute mortality was calculated , and relative risk was expressed as the ratio of the number of observed deaths to the number expected in the general population of Engl and and Wales . Forty six of the 73 deaths were due to coronary heart disease . In women aged 20 - 39 , despite treatment , the relative risk of a fatal coronary event was increased 125-fold ( 95 % confidence intervals 15 - 451 ) and the annual coronary mortality was 0.17 % . In men aged 20 - 39 the relative risk was increased 48-fold ( 17 - 105 ) and the annual coronary mortality was 0.46 % . The relative risk decreased with age but the absolute risk increased . For men and women aged 60 - 79 , the annual coronary mortality was 1.1 % representing a significant excess mortality for women ( relative risk 2.6 , 1.3 - 4.5 ) but not for men ( RR 1.1 , 0.5 - 2.3 ) . Non-coronary mortality was not increased at any age ( RR for all ages 0.68 , 0.45 - 0.99 ) . There was a decline in the relative risk for coronary mortality in patients aged 20 - 59 from an eight-fold ( 4.8 - 7.2 ) increased risk before 1992 to 3.7 ( 1.6 - 7.2 . ) thereafter ( P=0.08 ) . The results suggest that the prognosis for patients with heterozygous familial hypercholesterolaemia has improved with the introduction of more effective treatment , and that lipid-lowering therapy is not associated with increased non-coronary mortality . These findings and the excess coronary mortality observed suggest that all affected adult men and post-menopausal women should be treated with HMG-CoA reductase inhibitors ABSTRACT Objective : To assess the long term cost effectiveness of clopidogrel monotherapy compared with acetylsalicylic acid ( aspirin ; ASA ) monotherapy in patients at risk of secondary occlusive vascular events ( OVEs ) in the UK . Design : Cost utility analysis based on clinical data from CAPRIE ( a multicentre r and omised controlled trial , involving 19 185 patients ) ; long-term effects were extrapolated beyond the trial period using a Markov model populated with data from UK observational studies . Health economic evaluation carried out from the perspective of the UK National Health Service . Participants : A representative cohort of 1000 UK patients aged 60 years ( approximate mean age of the CAPRIE population ) , with the qualifying diagnoses of myocardial infa rct ion , ischaemic stroke and peripheral arterial disease , who are at risk of secondary OVEs ( non-fatal myocardial infa rct ion , non-fatal stroke or vascular death ) . Interventions : Patients were assumed to receive treatment with either clopidogrel ( 75 mg/day ) for 2 years followed by ASA ( 325 mg/day , average ) for their remaining lifetime , or ASA alone ( 325 mg/day , average ) for life . Main outcome measures : Incremental cost per life year gained and incremental cost per quality -adjusted life year ( QALY ) gained . Results : In the base case , the incremental cost effectiveness of clopidogrel versus ASA in this population is estimated at £ 18 888 per life year gained and £ 21 489 per QALY gained . Multiple deterministic and probabilistic sensitivity analyses suggest the model is robust to variations in a wide range of input parameters . Conclusion : Two years of treatment with clopidogrel can be considered a cost effective intervention in patients at risk of secondary OVEs in the UK CONTEXT Evidence suggests that more intensive lowering of low-density lipoprotein cholesterol ( LDL-C ) than is commonly applied clinical ly will provide further benefit in stable coronary artery disease . OBJECTIVE To compare the effects of 2 strategies of lipid lowering on the risk of cardiovascular disease among patients with a previous myocardial infa rct ion ( MI ) . DESIGN , SETTING , AND PARTICIPANTS The IDEAL study , a prospect i ve , r and omized , open-label , blinded end-point evaluation trial conducted at 190 ambulatory cardiology care and specialist practice s in northern Europe between March 1999 and March 2005 with a median follow-up of 4.8 years , which enrolled 8888 patients aged 80 years or younger with a history of acute MI . INTERVENTIONS Patients were r and omly assigned to receive a high dose of atorvastatin ( 80 mg/d ; n = 4439 ) , or usual-dose simvastatin ( 20 mg/d ; n = 4449 ) . MAIN OUTCOME MEASURE Occurrence of a major coronary event , defined as coronary death , confirmed nonfatal acute MI , or cardiac arrest with resuscitation . RESULTS During treatment , mean LDL-C levels were 104 ( SE , 0.3 ) mg/dL in the simvastatin group and 81 ( SE , 0.3 ) mg/dL in the atorvastatin group . A major coronary event occurred in 463 simvastatin patients ( 10.4 % ) and in 411 atorvastatin patients ( 9.3 % ) ( hazard ratio [ HR ] , 0.89 ; 95 % CI , 0.78 - 1.01 ; P = .07 ) . Nonfatal acute MI occurred in 321 ( 7.2 % ) and 267 ( 6.0 % ) in the 2 groups ( HR , 0.83 ; 95 % CI , 0.71 - 0.98 ; P = .02 ) , but no differences were seen in the 2 other components of the primary end point . Major cardiovascular events occurred in 608 and 533 in the 2 groups , respectively ( HR , 0.87 ; 95 % CI , 0.77 - 0.98 ; P = .02 ) . Occurrence of any coronary event was reported in 1059 simvastatin and 898 atorvastatin patients ( HR , 0.84 ; 95 % CI , 0.76 - 0.91 ; P<.001 ) . Noncardiovascular death occurred in 156 ( 3.5 % ) and 143 ( 3.2 % ) in the 2 groups ( HR , 0.92 ; 95 % CI , 0.73 - 1.15 ; P = .47 ) . Death from any cause occurred in 374 ( 8.4 % ) in the simvastatin group and 366 ( 8.2 % ) in the atorvastatin group ( HR , 0.98 ; 95 % CI , 0.85 - 1.13 ; P = .81 ) . Patients in the atorvastatin group had higher rates of drug discontinuation due to nonserious adverse events ; transaminase elevation result ed in 43 ( 1.0 % ) vs 5 ( 0.1 % ) withdrawals ( P<.001 ) . Serious myopathy and rhabdomyolysis were rare in both groups . CONCLUSIONS In this study of patients with previous MI , intensive lowering of LDL-C did not result in a significant reduction in the primary outcome of major coronary events , but did reduce the risk of other composite secondary end points and nonfatal acute MI . There were no differences in cardiovascular or all-cause mortality . Patients with MI may benefit from intensive lowering of LDL-C without an increase in noncardiovascular mortality or other serious adverse reactions . Trial Registration Clinical Trials.gov Identifier : NCT00159835 CONTEXT Although cholesterol-reducing treatment has been shown to reduce fatal and nonfatal coronary disease in patients with coronary heart disease ( CHD ) , it is unknown whether benefit from the reduction of low-density lipoprotein cholesterol ( LDL-C ) in patients without CHD extends to individuals with average serum cholesterol levels , women , and older persons . OBJECTIVE To compare lovastatin with placebo for prevention of the first acute major coronary event in men and women without clinical ly evident atherosclerotic cardiovascular disease with average total cholesterol ( TC ) and LDL-C levels and below-average high-density lipoprotein cholesterol ( HDL-C ) levels . DESIGN A r and omized , double-blind , placebo-controlled trial . SETTING Outpatient clinics in Texas . PARTICIPANTS A total of 5608 men and 997 women with average TC and LDL-C and below-average HDL-C ( as characterized by lipid percentiles for an age- and sex-matched cohort without cardiovascular disease from the National Health and Nutrition Examination Survey [ NHANES ] III ) . Mean ( SD ) TC level was 5.71 ( 0.54 ) mmol/L ( 221 [ 21 ] mg/dL ) ( 51 st percentile ) , mean ( SD ) LDL-C level was 3.89 ( 0.43 ) mmol/L ( 150 [ 17 ] mg/dL ) ( 60th percentile ) , mean ( SD ) HDL-C level was 0.94 ( 0.14 ) mmol/L ( 36 [ 5 ] mg/dL ) for men and 1.03 ( 0.14 ) mmol/L ( 40 [ 5 ] mg/dL ) for women ( 25th and 16th percentiles , respectively ) , and median ( SD ) triglyceride levels were 1.78 ( 0.86 ) mmol/L ( 158 [ 76 ] mg/dL ) ( 63rd percentile ) . INTERVENTION Lovastatin ( 20 - 40 mg daily ) or placebo in addition to a low-saturated fat , low-cholesterol diet . MAIN OUTCOME MEASURES First acute major coronary event defined as fatal or nonfatal myocardial infa rct ion , unstable angina , or sudden cardiac death . RESULTS After an average follow-up of 5.2 years , lovastatin reduced the incidence of first acute major coronary events ( 1 83 vs 116 first events ; relative risk [ RR ] , 0.63 ; 95 % confidence interval [ CI ] , 0.50 - 0.79 ; P<.001 ) , myocardial infa rct ion ( 95 vs 57 myocardial infa rct ions ; RR , 0.60 ; 95 % CI , 0.43 - 0.83 ; P=.002 ) , unstable angina ( 87 vs 60 first unstable angina events ; RR , 0.68 ; 95 % CI , 0.49 - 0.95 ; P=.02 ) , coronary revascularization procedures ( 157 vs 106 procedures ; RR , 0.67 ; 95 % CI , 0.52 - 0.85 ; P=.001 ) , coronary events ( 215 vs 163 coronary events ; RR , 0.75 ; 95 % CI , 0.61 - 0.92 ; P = .006 ) , and cardiovascular events ( 255 vs 194 cardiovascular events ; RR , 0.75 ; 95 % CI , 0.62 - 0.91 ; P = .003 ) . Lovastatin ( 20 - 40 mg daily ) reduced LDL-C by 25 % to 2.96 mmol/L ( 115 mg/dL ) and increased HDL-C by 6 % to 1.02 mmol/L ( 39 mg/dL ) . There were no clinical ly relevant differences in safety parameters between treatment groups . CONCLUSIONS Lovastatin reduces the risk for the first acute major coronary event in men and women with average TC and LDL-C levels and below-average HDL-C levels . These findings support the inclusion of HDL-C in risk-factor assessment , confirm the benefit of LDL-C reduction to a target goal , and suggest the need for re assessment of the National Cholesterol Education Program guidelines regarding pharmacological intervention OBJECTIVES This study sought to determine if an aggressive , focused low-density lipoprotein cholesterol (LDL-C)-lowering strategy was superior to usual care for coronary heart disease ( CHD ) patients enrolled in health maintenance organization or Veterans Administration setting s. BACKGROUND Statin therapy benefits are well established . No prospect i ve , r and omized studies have tested strategies to optimize these benefits in a " real-world " setting . METHODS A total of 2,442 CHD patients with hyperlipidemia were r and omized to either an aggressive treatment arm using atorvastatin or usual care and followed for 51.5 months on average . Atorvastatin-group patients were titrated to LDL-C goals of < 80 mg/dl ( 2.1 mmol/l ) or a maximum atorvastatin dose of 80 mg/day . Usual-care patients received any treatment deemed appropriate by their regular physicians . End point assessment s were complete in 958 atorvastatin-group and 941 usual-care patients . Partial assessment s occurred in 259 patients in the atorvastatin group and 284 patients in the usual care group who did not complete four years of study participation because of adverse events , withdrawn consent , or follow-up loss . The primary efficacy parameter was time to first cardiovascular event . RESULTS A total of 289 ( 23.7 % ) patients in the atorvastatin group compared with 333 ( 27.7 % ) patients in the usual care group experienced a primary outcome ( hazard ratio , 0.83 ; 95 % confidence interval 0.71 to 0.97 , p = 0.02 ) . This reduction in morbidity was largely due to fewer non-fatal myocardial infa rct ions ( 4.3 % vs. 7.7 % , p = 0.0002 ) . Levels of LDL-C were reduced more ( 34.3 % vs. 23.3 % , p < 0.0001 ) and National Cholesterol Education Program goals ( LDL-C < 100 mg/dl ) more likely met at end-of- study visits ( 72.4 % vs. 40.0 % ) in patients receiving atorvastatin compared with those receiving usual care . CONCLUSIONS An aggressive , focused statin therapy management strategy outperformed usual care in health maintenance organization and Veterans Administration clinic patients with CHD BACKGROUND Little is known about the cost-effectiveness of secondary prevention after percutaneous coronary intervention ( PCI ) . The aim of this study was to estimate the cost-effectiveness of statin therapy . METHODS A cost-effectiveness analysis was performed using data from the Lescol Intervention Prevention Study ( LIPS ) . In the LIPS trial , patients with normal-to-moderate hypercholesterolaemia who had undergone a first PCI were r and omised to receive either fluvastatin 40 mg twice-daily plus dietary counselling or dietary counselling alone . A Markov model was used to estimate the incremental costs per quality -adjusted life year ( QALY ) and life year gained ( LYG ) . Costs were based on prices and reimbursed charges , utility data were drawn from literature . Monte Carlo simulations and multivariate analysis were used to assess uncertainty . RESULTS Routine statin treatment costs an additional € 734 ( SD € 686 ) per patient over ten years compared with controls . It result ed in an additional 0.078 ( 0.047 ) QALYs or 0.082 ( 0.041 ) LYG . The incremental costs per QALY and LYG were € 9312 ( € 14,648 ) and € 8954 ( € 16,617 ) respectively . Anticipating a willingness to pay of € 20,000 per QALY , there is a 75.1 % chance that fluvastatin treatment is cost-effective . CONCLUSION Statin therapy with fluvastatin is economically efficient with regard to reducing heart disease in the Netherl and s when given routinely to all patients following PCI OBJECTIVES This study was design ed to evaluate the effect of pravastatin on progression of coronary atherosclerosis and ischemic events in patients with coronary artery disease and mild to moderate hyperlipidemia . BACKGROUND Few clinical trial data support the use of lipid-lowering therapy in patients with coronary artery disease and mild to moderate elevations in cholesterol levels . METHODS Four hundred eight patients ( mean age 57 years ) with coronary artery disease and low density lipoprotein ( LDL ) cholesterol > or = 130 mg/dl ( 3.36 mmol/liter ) but < 190 mg/dl ( [ 4.91 mmol/liter ] ) despite diet were r and omized in a 3-year study to receive pravastatin or placebo . Atherosclerosis progression was evaluated by quantitative coronary arteriography . RESULTS Baseline mean LDL cholesterol was 164 mg/dl ( 4.24 mmol/liter ) . Pravastatin decreased total and LDL cholesterol and triglyceride levels by 19 % , 28 % and 8 % , respectively , and increased high density lipoprotein cholesterol by 7 % ( p < or = 0.001 vs. placebo for all lipid variables ) . Progression of atherosclerosis was reduced by 40 % for minimal vessel diameter ( p = 0.04 ) , particularly in lesions < 50 % stenosis at baseline . There was a consistent although not statistically significant effect on mean diameter and percent diameter stenosis . There were also fewer new lesions in those assigned pravastatin ( p < or = 0.03 ) . Myocardial infa rct ion was reduced during active treatment ( 8 in the pravastatin group , 17 in the placebo group ; log-rank test , p < or = 0.05 ; 60 % risk reduction ) , with the benefit beginning to emerge after 1 year . CONCLUSIONS In patients with coronary artery disease and mild to moderate cholesterol elevations , pravastatin reduces progression of coronary atherosclerosis and myocardial infa rct ion . The time course of event reduction increases the potential for a relatively rapid decrease in the clinical manifestations of coronary artery disease with lipid lowering The Oxfordshire Community Stroke Project is a prospect i ve register of all new cases of stroke and transient ischemic attack ( TIA ) in a population of 105,000 residents of Oxfordshire , Engl and . Between November 1 , 1981 , and October 31 , 1986 , 184 patients presented for the first time to a general practitioner or hospital with a TIA . The crude annual incidence rate was 0.35/1000 , 0.42/1000 st and ardized to the 1981 population of Engl and and Wales . We estimate that each year approximately 21,000 patients in Engl and and Wales ( about half of whom are greater than 70 years old ) consult a doctor for the first time with a TIA . Approximately 80 % of our 184 patients had TIAs in the carotid distribution ; the remainder had TIAs in the vertebrobasilar distribution or TIAs of uncertain vascular distribution . The incidence of TIA increased sharply with increasing age , and the overall incidence in men was very similar to that in women ( incidence ratio 1.3 ) . However , in middle age , men were much more likely to suffer a TIA than women ( odds ratio 2.6 ) , which probably explains the marked male predominance in most hospital-based studies and treatment trials in which the elderly , and thus women , are underrepresented . This has important implication s for the design and interpretation of clinical trials of treatment for TIAs Those people who are to decide about health care systems are increasingly forced to identify unnecessary costs and achieve savings in health care . Especially for diseases with high prevalence like illnesses of the heart and the circulatory system preventive measures are very important . This economic analysis tries to clarify whether the secondary -preventive application of the HMG-CoA reductase-inhibitor pravastatin is , apart from the clinical benefit , economically justified in patients suffering from coronary heart disease with average cholesterol levels . In the case of this study , the underlying type of economic evaluation was an incremental cost-effectiveness analysis . The outcome was defined as costs per life-year saved . This retrospective study is based on the results of the CARE ( Cholesterol And Recurrent Events ) study which has been published elsewhere [ 21 ] . When calculating costs we took into account the perspective of 3rd party payers ( public health insurance ) in Germany . The calculation of cost-effectiveness was carried out for the whole study population in CARE as well as for all patients aged 60 or more years in the CARE study . This was done because the different groups vary by the numbers of avoided myocardial infa rct ions , strokes and loss of life years . Netcosts for pravastatin therapy , i.e. drug costs for pravastatin minus costs for avoided events , were about 9.54 Mio DM ( referring to 1,000 patients treated for a period of 5 years ) . Net-costs for patients aged 60 or more years were 8.18 Mio DM . The effectiveness was defined as the number of life years saved and amounted to 216 years of life saved ( YOLS ) in the overall study group . For patients aged 60 or more years we found that 358 years were saved . The costs per life years saved ( i.e. the net-costs of pravastatin therapy divided through the number of life years saved ) turned out to be 44,000 DM per person in the study group . For patients over 60 the costs were 23,000 DM . Lipid-lowering with pravastatin in the secondary prevention of coronary heart disease in Germany is cost-effective . In those patients aged 60 or more yeas the use of pravastatin is even more cost-effective than in all patients included in the CARE study Aims /hypothesis . The purpose of this study is to investigate the cost-effectiveness of simvastatin in diabetic patients , using prospect ively collected outcomes data from the Sc and inavian Simvastatin Survival Study . Methods . Diabetic patients were identified using two different classifications schemes : Clinical history ( diabetic , non-diabetic ) and the new American Diabetes Association definition ( diabetic , impaired fasting glucose , normal fasting glucose ) . The analysis is based on prospect ively collected data from the trial on hospitalization for cardiovascular problems , study drug utilization and mortality . The incremental cost per life year saved with simvastatin is estimated using costs from Sweden ( primary ) and other European countries . Results . Hospitalizations for cardiovascular problems were considerably reduced with simvastatin therapy , with the greatest differences in the diabetic subgroups . Reductions in hospitalizations in the diabetic group result ed in substantial hospital cost savings that offset 67 to 76 % of the drug cost ( depending on the classification used ) . For the diabetic patients , the estimates of the cost per life-year gained ranged from 1600 Euros ( based on clinical history ) to 3200 Euros ( based on American Diabetes Association ) using Swedish costs . In the other evaluated European countries treatment with simvastatin showed a favourable cost-effectiveness ratio independent of differences in local health care unit costs . Conclusion /interpretation . For all subgroups in the diabetic classification schemes , treatment with simvastatin result ed in estimates of cost per life-year gained that were well within the range generally considered to be cost effective . Based on the Sc and inavian Simvastatin Survival Study , simvastatin therapy provides good value for money in both diabetic and non-diabetic patients with cardiovascular disease . [ Diabetologia ( 1999 ) 42 : 1293–1301 Summary Background : Atorvastatin is very effective in reducing plasma low-density lipoprotein cholesterol ( LDL-C ) levels . However , there is no long-term survival study that evaluated this statin . Patients − Methods : To assess the effect of atorvastatin on morbidity and mortality ( total and coronary ) of patients with established coronary heart disease ( CHD ) , 1600 consecutive patients were r and omised either to atorvastatin or to ' usual ' medical care . The dose of atorvastatin was titrated from 10 to 80mg/day , in order to reach the National Cholesterol Education Program ( NCEP ) goal of LDL-C < 100mg/dl ( 2.6mmol/l ) . All patients were followed up for a mean period of 3 years . Main Outcome Measures : Primary endpoints of the study were defined as death , non-fatal myocardial infa rct ion , unstable angina , congestive heart failure , revascularisation ( coronary morbidity ) and stroke . Secondary endpoints were the safety and efficacy of the hypolipidaemic drugs as well as the cost-effectiveness of atorvastatin . Results : The mean dosage of atorvastatin was 24 mg/day . This statin reduced total cholesterol by 36 % , LDL-C by 46 % , triglycerides by 31 % , and non-high-density lipoprotein cholesterol ( non-HDL-C ) by 44 % , while it increased HDL-C by 7 % ; all these changes were significant . The NCEP LDL-C and non-HDL-C treatment goals were reached by 95 % ( n = 759 ) and 97 % ( n = 776 ) , respectively , of patients on atorvastatin . Only 14 % of the ' usual ' care patients received any hypolipidaemic drugs throughout the study and 3 % of them reached the NCEP LDL-C treatment goal . The cost per quality -adjusted life-year gained with atorvastatin was estimated at $ US 8350 . During this study 196 ( 24.5 % ) CHD patients on ' usual ' care had a CHD recurrent event or died vs. 96 ( 12 % ) CHD patients on atorvastatin ; risk ratio ( RR ) 0.49 , confidence interval ( CI ) 0.27 - 0.73 , p < 0.0001 . In detail , atorvastatin reduced , in comparison to ' usual ' care , total mortality ( RR 0.57 , CI 0.39 - 0.78 , p = 0.0021 ) , coronary mortality ( RR 0.53 , CI 0.29 - 0.74 , p = 0.0017 ) , coronary morbidity ( RR 0.46 , CI 0.25 - 0.71 , p < 0.0001 ) , and stroke ( RR 0.53 , CI 0.30 - 0.82 , p = 0.034 ) . All subgroups of patients ( women , those with diabetes mellitus , arterial hypertension , age 60 to 75 years , congestive heart failure , recent unstable angina or prior revascularisation ) benefited from treatment with atorvastatin . Withdrawal of patients because of side-effects from the atorvastatin group was low ( 0.75 % ) and similar to that of the ' usual ' care group ( 0.4 % ) . Conclusions : Long-term treatment of CHD patients with atorvastatin to achieve NCEP lipid targets significantly reduces total and coronary mortality , coronary morbidity and stroke , in comparison to patients receiving ' usual ' medical care . Treatment with atorvastatin is well tolerated and cost-effective BACKGROUND In patients with high cholesterol levels , lowering the cholesterol level reduces the risk of coronary events , but the effect of lowering cholesterol levels in the majority of patients with coronary disease , who have average levels , is less clear . METHODS In a double-blind trial lasting five years we administered either 40 mg of pravastatin per day or placebo to 4159 patients ( 3583 men and 576 women ) with myocardial infa rct ion who had plasma total cholesterol levels below 240 mg per deciliter ( mean , 209 ) and low-density lipoprotein ( LDL ) cholesterol levels of 115 to 174 mg per deciliter ( mean , 139 ) . The primary end point was a fatal coronary event or a nonfatal myocardial infa rct ion . RESULTS The frequency of the primary end point was 10.2 percent in the pravastatin group and 13.2 percent in the placebo group , an absolute difference of 3 percentage points and a 24 percent reduction in risk ( 95 percent confidence interval , 9 to 36 percent ; P = 0.003 ) . Coronary bypass surgery was needed in 7.5 percent of the patients in the pravastatin group and 10 percent of those in the placebo group , a 26 percent reduction ( P=0.005 ) , and coronary angioplasty was needed in 8.3 percent of the pravastatin group and 10.5 percent of the placebo group , a 23 percent reduction ( P=0.01 ) . The frequency of stroke was reduced by 31 percent ( P=0.03 ) . There were no significant differences in overall mortality or mortality from noncardiovascular causes . Pravastatin lowered the rate of coronary events more among women than among men . The reduction in coronary events was also greater in patients with higher pretreatment levels of LDL cholesterol . CONCLUSIONS These results demonstrate that the benefit of cholesterol-lowering therapy extends to the majority of patients with coronary disease who have average cholesterol levels BACKGROUND In patients with coronary heart disease and a broad range of cholesterol levels , cholesterol-lowering therapy reduces the risk of coronary events , but the effects on mortality from coronary heart disease and overall mortality have remained uncertain . METHODS In a double-blind , r and omized trial , we compared the effects of pravastatin ( 40 mg daily ) with those of a placebo over a mean follow-up period of 6.1 years in 9014 patients who were 31 to 75 years of age . The patients had a history of myocardial infa rct ion or hospitalization for unstable angina and initial plasma total cholesterol levels of 155 to 271 mg per deciliter . Both groups received advice on following a cholesterol-lowering diet . The primary study outcome was mortality from coronary heart disease . RESULTS Death from coronary heart disease occurred in 8.3 percent of the patients in the placebo group and 6.4 percent of those in the pravastatin group , a relative reduction in risk of 24 percent ( 95 percent confidence interval , 12 to 35 percent ; P<0.001 ) . Overall mortality was 14.1 percent in the placebo group and 11.0 percent in the pravastatin group ( relative reduction in risk , 22 percent ; 95 percent confidence interval , 13 to 31 percent ; P<0.001 ) . The incidence of all cardiovascular outcomes was consistently lower among patients assigned to receive pravastatin ; these outcomes included myocardial infa rct ion ( reduction in risk , 29 percent ; P<0.001 ) , death from coronary heart disease or nonfatal myocardial infa rct ion ( a 24 percent reduction in risk , P<0.001 ) , stroke ( a 19 percent reduction in risk , P=0.048 ) , and coronary revascularization ( a 20 percent reduction in risk , P<0.001 ) . The effects of treatment were similar for all predefined subgroups . There were no clinical ly significant adverse effects of treatment with pravastatin . CONCLUSIONS Pravastatin therapy reduced mortality from coronary heart disease and overall mortality , as compared with the rates in the placebo group , as well as the incidence of all prespecified cardiovascular events in patients with a history of myocardial infa rct ion or unstable angina who had a broad range of initial cholesterol levels BACKGROUND Stroke is the most feared complication of thrombolysis for acute myocardial infa rct ion because of the result ing mortality and disability . We analyzed the incidence , timing , and outcomes of stroke in an international trial . METHODS AND RESULTS Patients were r and omly assigned to one of four thrombolytic strategies . Neurological events were confirmed clinical ly and anatomically and were adjudicated by a blinded committee . Stroke survivors , categorized by residual deficit and disability , assessed their quality of life with a time trade-off technique . Multivariable regression identified patient characteristics associated with intracranial hemorrhage . Over-all , 1.4 % of the patients had a stroke ( 93 % anatomic documentation ) . The risk ranged from 1.19 % with streptokinase/subcutaneous heparin therapy to 1.64 % with combination thrombolytic therapy ( P = .007 ) . Primary intracranial hemorrhage rates ranged from 0.46 % with streptokinase/subcutaneous heparin to 0.88 % with combination therapy ( P < .001 ) . Of all strokes , 41 % were fatal , 31 % were disabling , and 24 % were nondisabling , with no significant treatment-related differences . Stroke subtype affected prognosis : 60 % of patients with primary intracranial hemorrhage died and 25 % were disabled versus 17 % dead and 40 % disabled with nonhemorrhagic infa rct ions . Patients with moderate or severe residual deficits showed significantly decreased quality of life . Advanced age , lower weight , prior cerebrovascular disease or hypertension , systolic and diastolic blood pressures , r and omization to tissue plasminogen activator , and an interaction between age and hypertension were significant predictors of intracranial hemorrhage . CONCLUSIONS Stroke remains a rare but catastrophic complication of thrombolysis . Additional studies should assess the net clinical benefit of thrombolysis in high-risk subgroups , particularly the elderly and patients with prior cerebrovascular events Abstract Objective : To estimate the economic efficiency of using pravastatin to prevent the transition from health to cardiovascular disease in men with hypercholesterolaemia . Design : Economic benefit analysis based on data from the West of Scotl and coronary prevention study . Treatment specific hazards of developing cardiovascular disease according to various definitions were estimated . Scottish record linkage data provided disease specific survival . Cost estimates were based on extracontractual tariffs and event specific average lengths of stay calculated from the West of Scotl and coronary prevention study . Subjects : Men with hypercholesterolaemia similar to the subjects in the West of Scotl and coronary prevention study . Main outcome : Cost consequences , the number of transitions from health to cardiovascular disease prevented , the number needed to start treatment , and cost per life year gained . Results : If 10 000 of these men started taking pravastatin , 318 of them would not make the transition from health to cardiovascular disease ( number needed to treat , 31.4 ) , at a net discounted cost of £ 20 m over 5 years . These benefits imply an undiscounted gain of 2460 years of life , and thus £ 8121 per life year gained , or £ 20 375 per life year gained if benefits are discounted . Restriction to the 40 % of men at highest risk reduces the number needed to treat to 22.5 ( £ 5601 per life year gained ( undiscounted ) and £ 13 995 per life year gained ( discounted ) ) . Conclusions : In subjects without evidence of prior myocardial infa rct ion but who have hypercholesterolaemia , the use of pravastatin yields substantial health benefits at a cost that is not prohibitive overall and can be quite efficient in selected high risk subgroups . Key messages The West of Scotl and coronary prevention study showed that pravastatin can prevent cardiovascular disease in men with hypercholesterolaemia So far , reports have deemed this prevention unjustified due to adverse economic implication s This analysis , based on data from the West of Scotl and coronary prevention study and extensive data from the Scottish record linkage system , shows that using pravastatin in this way is worth considering because of its substantial clinical benefit at a reasonable cost Practitioners must now consider using pravastatin to prevent cardiovascular disease in men with hypercholesterolaemia Increased economic efficiency may be obtained by restricting prevention to patients with additional risk BACKGROUND Previous trials have demonstrated that lowering low-density lipoprotein ( LDL ) cholesterol levels below currently recommended levels is beneficial in patients with acute coronary syndromes . We prospect ively assessed the efficacy and safety of lowering LDL cholesterol levels below 100 mg per deciliter ( 2.6 mmol per liter ) in patients with stable coronary heart disease ( CHD ) . METHODS A total of 10,001 patients with clinical ly evident CHD and LDL cholesterol levels of less than 130 mg per deciliter ( 3.4 mmol per liter ) were r and omly assigned to double-blind therapy and received either 10 mg or 80 mg of atorvastatin per day . Patients were followed for a median of 4.9 years . The primary end point was the occurrence of a first major cardiovascular event , defined as death from CHD , nonfatal non-procedure-related myocardial infa rct ion , resuscitation after cardiac arrest , or fatal or nonfatal stroke . RESULTS The mean LDL cholesterol levels were 77 mg per deciliter ( 2.0 mmol per liter ) during treatment with 80 mg of atorvastatin and 101 mg per deciliter ( 2.6 mmol per liter ) during treatment with 10 mg of atorvastatin . The incidence of persistent elevations in liver aminotransferase levels was 0.2 percent in the group given 10 mg of atorvastatin and 1.2 percent in the group given 80 mg of atorvastatin ( P<0.001 ) . A primary event occurred in 434 patients ( 8.7 percent ) receiving 80 mg of atorvastatin , as compared with 548 patients ( 10.9 percent ) receiving 10 mg of atorvastatin , representing an absolute reduction in the rate of major cardiovascular events of 2.2 percent and a 22 percent relative reduction in risk ( hazard ratio , 0.78 ; 95 percent confidence interval , 0.69 to 0.89 ; P<0.001 ) . There was no difference between the two treatment groups in overall mortality . CONCLUSIONS Intensive lipid-lowering therapy with 80 mg of atorvastatin per day in patients with stable CHD provides significant clinical benefit beyond that afforded by treatment with 10 mg of atorvastatin per day . This occurred with a greater incidence of elevated aminotransferase levels PURPOSE To compare the cost-effectiveness of surgical and angioplasty-based coronary artery revascularization techniques , in particular , angioplasty with primary stenting . METHODS We used data from the Study of Economics and Quality of Life , a sub study of the Bypass Angioplasty Revascularization Investigation ( BARI ) , to measure the outcomes and costs of angioplasty and bypass surgery in patients with multivessel coronary artery disease who had not undergone prior coronary artery revascularization . Using a Markov decision model , we up date d the outcomes and costs to reflect technology changes since the time of enrollment in BARI , and projected the lifetime costs and quality -adjusted life-years ( QALYs ) for the two procedures from the time of initial treatment through death . We accounted for the effects of improved procedural safety and efficiency , and prolonged therapeutic effects of both surgery and stenting . This study was conducted from a societal perspective . RESULTS Surgical revascularization was less costly and result ed in better outcomes than catheter-based intervention including stenting . It remained the preferred strategy after adjusting the stent outcomes to eliminate the costs and events associated with target lesion restenosis . Among angioplasty-based strategies , primary stent use cost an additional 189,000 US dollars per QALY gained compared with a strategy that reserved stent use for treatment of suboptimal balloon angioplasty results . CONCLUSION Bypass surgery results in better outcomes than angioplasty in patients with multivessel disease , and at a lower cost Purpose Normative data for WHOQOL-bref are scarce in the literature and unavailable in Latin American countries . The main objective of this study was to provide normative scores of WHOQOL-bref in a general population sample in Brazil and to describe differences in mean scores according to some socio-demographic characteristics . Methods WHOQOL-bref was applied to a r and omly selected sample of the general population of Porto Alegre . Participants were literate people aged 20 to 64 years . The question naires were self-administered in the presence of an interviewer in the respondent ’s home . Results The response rate was 68 % , and the final sample contained 751 respondents ( 38 % men , 62 % women ) . Low quality of life was observed in the following subgroups : female gender , lower economic class , lower educational level , and the subgroup reporting a chronic medical condition . The mean scores of the WHOQOL-bref and percentiles of scores are reported as normative data for the general population . Conclusion Our results can be useful to research ers using the WHOQOL-bref to compare their results with normative data from a r and omly selected sample of general population . Additionally , the ability of WHOQOL-bref to discriminate different population subgroups makes it an important tool to identify vulnerable groups in epidemiological surveys Aims To develop a model for estimating the immediate and long‐term healthcare costs associated with seven diabetes‐related complications in patients with Type 2 diabetes participating in the UK Prospect i ve Diabetes Study ( UKPDS ) Abstract Aims : To estimate the costs , benefits and cost effectiveness , from the UK NHS perspective , of fluvastatin ( relative to no HMG-CoA reductase inhibitor [ statin ] ) for the secondary prevention of major adverse cardiac events following a successful first percutaneous coronary intervention ( PCI ) . Methods : A cost-effectiveness analysis was undertaken using efficacy data from the Lescol ® Intervention Prevention Study ( LIPS ) . LIPS was a r and omised , double-blind , placebo-controlled trial undertaken in 77 centres ( predominantly in Europe ) . Patients included in the trial had moderate hypercholesterolaemia and had successfully undergone their first PCI . Fluvastatin ( Lescol ® ) 40 mg twice daily plus dietary counselling was given to the intervention group for up to 4 years ; the control group received dietary counselling only . A Markov model was used to estimate the incremental costs per QALY gained over a 10-year period , with cost data drawn from the UK NHS ( 2002 values ) . Monte Carlo simulations and multivariate analysis were used to assess uncertainty . Costs were discounted at 6 % per annum , and health outcomes at 1.5 % per annum . Results : On average , treatment with fluvastatin cost an additional £ 300 ( SD £ 303 ) [ € 423 ; SD € 428 ] per patient and result ed in an additional 0.092 ( SD 0.06 ) QALYs per patient over 10 years compared with controls . The incremental cost per QALY gained with fluvastatin versus the control group was £ 3207 ( SD £ 5497 ) [ € 4527 ; SD € 7759 ] . Fluvastatin was dominant ( better outcomes and lower costs ) in 15.9 % of the simulations and was dominated in 2.9 % . The key determinants of cost effectiveness were : the effectiveness of fluvastatin in reducing acute myocardial infa rct ion , subsequent PCI , coronary artery bypass graft and cardiac deaths ; the utility weight associated with a subsequent post-PCI state ; the cost of fluvastatin ; and the time horizon evaluated . Conclusions : Fluvastatin is the only statin which has proven effective in preventing major coronary adverse events in new PCI patients ; other statins lack this evidence . This Markov model , with its underlying assumptions and data , suggests that fluvastatin is a viable and economically efficient pharmaceutical ( relative to no statin ) to reduce heart disease in the UK when given routinely to all patients following PCI BACKGROUND Stroke occurs concurrently with myocardial infa rct ion ( MI ) in approximately 30 000 US patients each year . This number is expected to rise with the increasing use of thrombolytic therapy for MI . However , no data exist for the economic effect of stroke in the setting of acute MI ( AMI ) . The purpose of this prospect i ve study was to assess the effect of stroke on medical re source use and costs in AMI patients in the United States . METHODS AND RESULTS Medical re source use and cost data were prospect ively collected for 2566 r and omly selected US GUSTO I patients ( from 23 105 patients ) and for the 321 US GUSTO I patients who developed non-bypass surgery-related stroke during the baseline hospitalization . Follow-up was for 1 year . All costs are expressed in 1993 US dollars . During the baseline hospitalization , stroke was associated with a reduction in cardiac procedure rates and an increase in length of stay , despite a hospital mortality rate of 37 % . Together with stroke-related procedural costs of $ 2220 per patient , the baseline medical costs increased by 44 % ( $ 29 242 versus $ 20 301 , P<0.0001 ) . Follow-up medical costs were substantially higher for stroke survivors ( $ 22 400 versus $ 5282 , P<0.0001 ) , dominated by the cost of institutional care . The main determinant for institutional care was discharge disability status . The cumulative 1-year medical costs for stroke patients were $ 15 092 higher than for no-stroke patients . Hemorrhagic stroke patients had a much higher hospital mortality rate than non-hemorrhagic stroke patients ( 53 % versus 15 % , P<0.001 ) , which was associated with approximately $ 7200 lower mean baseline hospitalization cost . At discharge , hemorrhagic stroke patients were more likely to be disabled ( 68 % versus 46 % , P=0.002 ) . CONCLUSIONS In this first large prospect i ve economic study of stroke in AMI patients , we found that strokes were associated with a 60 % ( $ 15 092 ) increase in cumulative 1-year medical costs . Baseline hospitalization costs were 44 % higher because of longer mean lengths of stay . Stroke type was a key determinant of baseline cost . Follow-up costs were more than quadrupled for stroke survivors because of the need for institutional care . Disability level was the main determinant of institutional care and thus of follow-up costs OBJECTIVE To examine the cost-effectiveness of prescribing warfarin sodium in patients who have nonvalvular atrial fibrillation ( NVAF ) with or without additional stroke risk factors ( a prior stroke or transient ischemic attack , diabetes , hypertension , or heart disease ) . DESIGN Decision and cost-effectiveness analyses . The probabilities for stroke , hemorrhage , and death were obtained from published r and omized controlled trials . The quality -of-life estimates were obtained by interviewing 74 patients with atrial fibrillation . Costs were estimated from literature review , phone survey , and Medicare reimbursement . PATIENTS In the base case , the patients were 65 years of age and good c and i date s for warfarin therapy . INTERVENTIONS Treatment with warfarin , aspirin , or no therapy in the decision analytic model . MAIN OUTCOME MEASURES Quality -adjusted survival and marginal cost-effectiveness of warfarin as compared with aspirin or no therapy . RESULTS For patients with NVAF and additional risk factors for stroke , warfarin therapy led to a greater quality -adjusted survival and to cost savings . For patients with NVAF and one additional risk factor , warfarin therapy cost $ 8000 per quality -adjusted life-year saved . For 65-year-old patients with NVAF alone , warfarin cost about $ 370,000 per quality -adjusted life-year saved , as compared with aspirin therapy . However , for 75-year-old patients with NVAF alone , prescribing warfarin cost $ 110,000 per quality -adjusted life-year saved . For patients who were not prescribed warfarin , aspirin was preferred to no therapy on the basis of both quality -adjusted survival and cost in all patients , regardless of the number of risk factors present . CONCLUSIONS Treatment with warfarin is cost-effective in patients with NVAF and one or more additional risk factors for stroke . In 65-year-old patients with NVAF but no other risk factors for stroke , prescribing warfarin instead of aspirin would affect quality -adjusted survival minimally but increase costs significantly Background The Lescol Intervention Prevention Study ( LIPS ) showed substantial gains in health outcomes from statins following PCI . That study was a r and omized double-blind placebo-controlled trial undertaken in 77 centres , predominantly in Europe , of patients with moderate hypercholesterolemia who had undergone their first PCI . The evidence on cost-effectiveness has been established for the UK , USA and the Netherl and s , but due to different health system cost structures , the results may not be applicable to other European countries . The aim of this study was to estimate the cost-effectiveness of fluvastatin used following first PCI in Hungary . Material s and methods A deterministic Markov model was used to estimate the incremental costs per quality -adjusted life year gained , with cost data drawn from the Hungarian National Health Insurance Fund . Effectiveness data on fluvastatin was derived directly from LIPS and utility weights from previous studies on heart disease . Sensitivity analyses were conducted around key parameters and analyses were conducted for subgroups identified in LIPS . Results Treatment with fluvastatin cost an additional € 1,704 and result ed in an additional 0.107 QALYs per patient discounted over 10-years compared with controls . The incremental cost per quality -adjusted life year gained was € 15,910 . The key determinants of cost-effectiveness were the effectiveness of fluvastatin , utility weights , cost of fluvastatin , and the time horizon evaluated . Fluvastatin was substantially more cost-effective in patients with diabetes , renal disease , multi-vessel disease or LDL-cholesterol > 3.4 mmol/l . Conclusions Fluvastatin is an economically efficient pharmaceutical for reducing heart disease in Hungary and other European countries in patients following PCI BACKGROUND Throughout the usual LDL cholesterol range in Western population s , lower blood concentrations are associated with lower cardiovascular disease risk . In such population s , therefore , reducing LDL cholesterol may reduce the development of vascular disease , largely irrespective of initial cholesterol concentrations . METHODS 20,536 UK adults ( aged 40 - 80 years ) with coronary disease , other occlusive arterial disease , or diabetes were r and omly allocated to receive 40 mg simvastatin daily ( average compliance : 85 % ) or matching placebo ( average non- study statin use : 17 % ) . Analyses are of the first occurrence of particular events , and compare all simvastatin-allocated versus all placebo-allocated participants . These " intention-to-treat " comparisons assess the effects of about two-thirds ( 85 % minus 17 % ) taking a statin during the scheduled 5-year treatment period , which yielded an average difference in LDL cholesterol of 1.0 mmol/L ( about two-thirds of the effect of actual use of 40 mg simvastatin daily ) . Primary outcomes were mortality ( for overall analyses ) and fatal or non-fatal vascular events ( for subcategory analyses ) , with subsidiary assessment s of cancer and of other major morbidity . FINDINGS All-cause mortality was significantly reduced ( 1328 [ 12.9 % ] deaths among 10,269 allocated simvastatin versus 1507 [ 14.7 % ] among 10,267 allocated placebo ; p=0.0003 ) , due to a highly significant 18 % ( SE 5 ) proportional reduction in the coronary death rate ( 587 [ 5.7 % ] vs 707 [ 6.9 % ] ; p=0.0005 ) , a marginally significant reduction in other vascular deaths ( 194 [ 1.9 % ] vs 230 [ 2.2 % ] ; p=0.07 ) , and a non-significant reduction in non-vascular deaths ( 547 [ 5.3 % ] vs 570 [ 5.6 % ] ; p=0.4 ) . There were highly significant reductions of about one-quarter in the first event rate for non-fatal myocardial infa rct ion or coronary death ( 898 [ 8.7 % ] vs 1212 [ 11.8 % ] ; p<0.0001 ) , for non-fatal or fatal stroke ( 444 [ 4.3 % ] vs 585 [ 5.7 % ] ; p<0.0001 ) , and for coronary or non-coronary revascularisation ( 939 [ 9.1 % ] vs 1205 [ 11.7 % ] ; p<0.0001 ) . For the first occurrence of any of these major vascular events , there was a definite 24 % ( SE 3 ; 95 % CI 19 - 28 ) reduction in the event rate ( 2033 [ 19.8 % ] vs 2585 [ 25.2 % ] affected individuals ; p<0.0001 ) . During the first year the reduction in major vascular events was not significant , but subsequently it was highly significant during each separate year . The proportional reduction in the event rate was similar ( and significant ) in each subcategory of participant studied , including : those without diagnosed coronary disease who had cerebrovascular disease , or had peripheral artery disease , or had diabetes ; men and , separately , women ; those aged either under or over 70 years at entry ; and --most notably -- even those who presented with LDL cholesterol below 3.0 mmol/L ( 116 mg/dL ) , or total cholesterol below 5.0 mmol/L ( 193 mg/dL ) . The benefits of simvastatin were additional to those of other cardioprotective treatments . The annual excess risk of myopathy with this regimen was about 0.01 % . There were no significant adverse effects on cancer incidence or on hospitalisation for any other non-vascular cause . INTERPRETATION Adding simvastatin to existing treatments safely produces substantial additional benefits for a wide range of high-risk patients , irrespective of their initial cholesterol concentrations . Allocation to 40 mg simvastatin daily reduced the rates of myocardial infa rct ion , of stroke , and of revascularisation by about one-quarter . After making allowance for non-compliance , actual use of this regimen would probably reduce these rates by about one-third . Hence , among the many types of high-risk individual studied , 5 years of simvastatin would prevent about 70 - 100 people per 1000 from suffering at least one of these major vascular events ( and longer treatment should produce further benefit ) . The size of the 5-year benefit depends chiefly on such individuals ' overall risk of major vascular events , rather than on their blood lipid concentrations alone BACKGROUND Although it is generally accepted that lowering elevated serum levels of low-density lipoprotein ( LDL ) cholesterol in patients with coronary heart disease is beneficial , there are few data to guide decisions about therapy for patients whose primary lipid abnormality is a low level of high-density lipoprotein ( HDL ) cholesterol . METHODS We conducted a double-blind trial comparing gemfibrozil ( 1200 mg per day ) with placebo in 2531 men with coronary heart disease , an HDL cholesterol level of 40 mg per deciliter ( 1.0 mmol per liter ) or less , and an LDL cholesterol level of 140 mg per deciliter ( 3.6 mmol per liter ) or less . The primary study outcome was nonfatal myocardial infa rct ion or death from coronary causes . RESULTS The median follow-up was 5.1 years . At one year , the mean HDL cholesterol level was 6 percent higher , the mean triglyceride level was 31 percent lower , and the mean total cholesterol level was 4 percent lower in the gemfibrozil group than in the placebo group . LDL cholesterol levels did not differ significantly between the groups . A primary event occurred in 275 of the 1267 patients assigned to placebo ( 21.7 percent ) and in 219 of the 1264 patients assigned to gemfibrozil ( 17.3 percent ) . The overall reduction in the risk of an event was 4.4 percentage points , and the reduction in relative risk was 22 percent ( 95 percent confidence interval , 7 to 35 percent ; P=0.006 ) . We observed a 24 percent reduction in the combined outcome of death from coronary heart disease , nonfatal myocardial infa rct ion , and stroke ( P < 0.001 ) . There were no significant differences in the rates of coronary revascularization , hospitalization for unstable angina , death from any cause , and cancer . CONCLUSIONS Gemfibrozil therapy result ed in a significant reduction in the risk of major cardiovascular events in patients with coronary disease whose primary lipid abnormality was a low HDL cholesterol level . The findings suggest that the rate of coronary events is reduced by raising HDL cholesterol levels and lowering levels of triglycerides without lowering LDL cholesterol levels BACKGROUND Surgical techniques of myocardial revascularization without the use of extracorporeal circulation ( ECC ) have raised hopes of attaining operative results with less systemic damage , lower occurrence of clinical complications and shorter hospital stay duration , generating expectations of lower hospital costs . OBJECTIVE To evaluate the hospital costs in patients su bmi tted to myocardial revascularization with and without ECC and in those with stable multiarterial coronary disease with preserved ventricular function . METHODS The hospital costs were based on the existing governmental reimbursement . The costs included that of ortheses and prostheses and clinical complications . The time and costs of ICU stay and hospital stay duration were considered . RESULTS Between January 2002 and August 2006 , 131 patients were r and omized to surgery with ECC ( SECC ) , whereas 128 were r and omized to surgery without ECC ( WECC ) . The basal characteristics were similar for both groups . The costs of surgical complications were significantly lower ( p < 0.001 ) in patients from the WECC when compared to the SECC group ( 606.00 + /- 525.00 vs. 945.90 + /- 440.00 ) , as well as ICU costs : 432.20 + /- 391.70 vs. 717.70 + /- 257.70 , respectively . The duration of the operating room stay were 4.9 + /- 1.1 h vs. 3.9 + /- 1.0 h , p < 0.001 ; at the ICU it was 48.2 + /- 17.2 h vs. 29.2 + /- 26.1h ) ( p < 0.001 ) , with intubation time of 9.2 + /- 4.5 h vs. 6.4 + /- 5.1h , p < 0.001 for patients from the group with and without ECC , respectively . CONCLUSION The present study allowed us to conclude that the myocardial revascularization surgery without extracorporeal circulation results in the decrease of operational costs and duration of the stay in each section related to the surgical treatment Abstract Aim : To estimate the cost of treating stroke in the UK . Methods : A cost-of-illness model was constructed to estimate stroke-related costs over a 5-year period . The cost estimates were based on data from a large , r and omised , prospect i ve study comparing alternative strategies of stroke care . The study collected detailed data on re source use in hospital , primary care , healthcare contacts , and utilisation of social services over a period of 1 year following stroke . A Markov framework was used to extrapolate 1-year costs over 5 years . Results : The model estimated that , for every patient who experiences a stroke , the cost to the NHS in the UK is £ 15 306 over 5 years and , when informal care costs are included , the amount increases to £ 29 405 ( 2001/2002 prices ) . The robustness of the cost findings was explored with the use of sensitivity analysis . This focused on the key variables of rates of recurrent stroke , the estimated acute costs , and costs attached to institution and home care . Conclusion : As well as being a considerable cause of morbidity and mortality , stroke is also a huge cost burden to both the UK ’s NHS and the carers of stroke victims OBJECTIVE To determine the cost-effectiveness of specialist nurse-led clinics provided to improve lipid and blood pressure control in diabetic patients receiving hospital-based care . RESEARCH DESIGN AND METHODS A policy of targeting improved care through specialist nurse-led clinics is evaluated using a novel method , linking the cost-effectiveness of antihypertensive and lipid-lowering treatments with the cost and level of behavioral change achieved by the specialist nurse-led clinics . Treatment cost-effectiveness is modeled from the U.K. Prospect i ve Diabetes Study and Heart Protection Study treatment trials , whereas specialist nurse-led clinics are evaluated using the Specialist Nurse-Led Clinics to Improve Control of Hypertension and Hyperlipidemia in Diabetes ( SPLINT ) trial . RESULTS Good lipid and blood pressure control are cost-effective treatment goals for patients with diabetes . Modeling findings from treatment trials , blood pressure lowering is estimated to be cost saving and life prolonging ( -1,400 dollars/ quality -adjusted life-year [ QALY ] ) , whereas lipid-lowering is estimated to be highly cost-effective ( 8,230 dollars/QALY ) . Investing in nurse-led clinics to help achieve these benefits imposes an addition on treatment cost-effectiveness leading to higher estimates : 4,020 dollars/QALY and 19,950 dollars/QALY , respectively . For both clinics combined , the estimated cost-effectiveness is 9,070 dollars/QALY . Using an acceptability threshold of 50,000 dollars/QALY , the likelihood that blood pressure-lowering clinics are cost-effective is 77 % , lipid clinics 99 % , and combined clinics 83 % . CONCLUSIONS A method is described for evaluating the cost-effectiveness of policies to change patient uptake of health care . Such policies are less attractive than treatment cost-effectiveness ( which implies cost-less self-implementation ) . However , specialist nurse-led clinics , as an adjunct to hospital-based diabetic care , combining both lipid and blood pressure control , appear effective and likely to provide excellent value for money Changes between 1972 and 1982 in the use of in-hospital services were studied for 164 patients admitted with acute myocardial infa rct ion . Re source use was measured in constant 1982 dollars adjusted for differences in clinical severity of the patients . Although average length of stay decreased by almost 40 % during this period , the number of physician services doubled and total physician costs increased almost threefold . The increase in physician costs was due primarily to the use of complex diagnostic technologies and to the provision of coronary artery bypass graft surgery . The results of this study suggest that as hospital costs are constrained by prospect i ve payment , physician costs may continue to rise as new diagnostic and therapeutic services are introduced into practice and as more care is shifted to the outpatient setting BACKGROUND Intensive lowering of serum cholesterol may retard progression of coronary atherosclerosis in selected groups of patients . However , few data are available on the potential benefit of serum cholesterol reduction in the broad range of patients with coronary atherosclerosis and normal to moderately elevated serum cholesterol levels who undergo various forms of treatment . The Regression Growth Evaluation Statin Study ( REGRESS ) addresses this group of patients . METHODS AND RESULTS REGRESS is a double-blind , placebo-controlled multicenter study to assess the effects of 2 years of treatment with the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor pravastatin on progression and regression of coronary atherosclerosis in 885 male patients with a serum cholesterol level between 4 and 8 mmol/L ( 155 and 310 mg/dL ) by quantitative coronary arteriography . Primary end points were ( 1 ) change in average mean segment diameter per patient and ( 2 ) change in average minimum obstruction diameter per patient . Clinical events were also analyzed . Of the 885 patients , 778 ( 88 % ) had an evaluable final angiogram . Mean segment diameter decreased 0.10 mm in the placebo group versus 0.06 mm in the pravastatin group ( P = .019 ) : The mean difference between treatment groups was 0.04 mm , with a 95 % CI of 0.01 to 0.07 mm . The median minimum obstruction diameter decreased 0.09 mm in the placebo group versus 0.03 mm in the pravastatin group ( P = .001 ) : The difference of the medians between the treatment groups was 0.06 mm , with a CI of 0.02 to 0.08 mm . At the end of the follow-up period , 89 % ( CI , 86 % to 92 % ) of the pravastatin patients and 81 % ( CI , 77 % to 85 % ) of the placebo patients were without new cardiovascular events ( P = .002 ) . CONCLUSIONS In symptomatic men with significant coronary atherosclerosis and normal to moderately elevated serum cholesterol , less progression of coronary atherosclerosis and fewer new cardiovascular events were observed in the group of patients treated with pravastatin than in the placebo group CONTEXT Limited data are available evaluating how the timing and intensity of statin therapy following an acute coronary syndrome ( ACS ) event affect clinical outcome . OBJECTIVE To compare early initiation of an intensive statin regimen with delayed initiation of a less intensive regimen in patients with ACS . DESIGN , SETTING , AND PARTICIPANTS International , r and omized , double-blind trial of patients with ACS receiving 40 mg/d of simvastatin for 1 month followed by 80 mg/d thereafter ( n = 2265 ) compared with ACS patients receiving placebo for 4 months followed by 20 mg/d of simvastatin ( n = 2232 ) , who were enrolled in phase Z of the A to Z trial between December 29 , 1999 , and January 6 , 2003 . MAIN OUTCOME MEASURE The primary end point was a composite of cardiovascular death , nonfatal myocardial infa rct ion , readmission for ACS , and stroke . Follow-up was for at least 6 months and up to 24 months . RESULTS Among the patients in the placebo plus simvastatin group , the median low-density lipoprotein ( LDL ) cholesterol level achieved while taking placebo was 122 mg/dL ( 3.16 mmol/L ) at 1 month and was 77 mg/dL ( 1.99 mmol/L ) at 8 months while taking 20 mg/d of simvastatin . Among the patients in the simvastatin only group , the median LDL cholesterol level achieved at 1 month while taking 40 mg/d of simvastatin was 68 mg/dL ( 1.76 mmol/L ) and was 63 mg/dL ( 1.63 mmol/L ) at 8 months while taking 80 mg/d of simvastatin . A total of 343 patients ( 16.7 % ) in the placebo plus simvastatin group experienced the primary end point compared with 309 ( 14.4 % ) in the simvastatin only group ( 40 mg/80 mg ) ( hazard ratio [ HR ] , 0.89 ; 95 % confidence interval [ CI ] 0.76 - 1.04 ; P = .14 ) . Cardiovascular death occurred in 109 ( 5.4 % ) and 83 ( 4.1 % ) patients in the 2 groups ( HR , 0.75 ; 95 % CI , 0.57 - 1.00 ; P = .05 ) but no differences were observed in other individual components of the primary end point . No difference was evident during the first 4 months between the groups for the primary end point ( HR , 1.01 ; 95 % CI , 0.83 - 1.25 ; P = .89 ) , but from 4 months through the end of the study the primary end point was significantly reduced in the simvastatin only group ( HR , 0.75 ; 95 % CI , 0.60 - 0.95 ; P = .02 ) . Myopathy ( creatine kinase > 10 times the upper limit of normal associated with muscle symptoms ) occurred in 9 patients ( 0.4 % ) receiving simvastatin 80 mg/d , in no patients receiving lower doses of simvastatin , and in 1 patient receiving placebo ( P = .02 ) . CONCLUSIONS The trial did not achieve the prespecified end point . However , among patients with ACS , the early initiation of an aggressive simvastatin regimen result ed in a favorable trend toward reduction of major cardiovascular events BACKGROUND Lowering the blood cholesterol level may reduce the risk of coronary heart disease . This double-blind study was design ed to determine whether the administration of pravastatin to men with hypercholesterolemia and no history of myocardial infa rct ion reduced the combined incidence of nonfatal myocardial infa rct ion and death from coronary heart disease . METHODS We r and omly assigned 6595 men , 45 to 64 years of age , with a mean ( + /- SD ) plasma cholesterol level of 272 + /- 23 mg per deciliter ( 7.0 + /- 0.6 mmol per liter ) to receive pravastatin ( 40 mg each evening ) or placebo . The average follow-up period was 4.9 years . Medical records , electrocardiographic recordings , and the national death registry were used to determine the clinical end points . RESULTS Pravastatin lowered plasma cholesterol levels by 20 percent and low-density-lipoprotein cholesterol levels by 26 percent , whereas there was no change with placebo . There were 248 definite coronary events ( specified as nonfatal myocardial infa rct ion or death from coronary heart disease ) in the placebo group , and 174 in the pravastatin group ( relative reduction in risk with pravastatin , 31 percent ; 95 percent confidence interval , 17 to 43 percent ; P < 0.001 ) . There were similar reductions in the risk of definite nonfatal myocardial infa rct ions ( 31 percent reduction , P < 0.001 ) , death from coronary heart disease ( definite cases alone : 28 percent reduction , P = 0.13 ; definite plus suspected cases : 33 percent reduction , P = 0.042 ) , and death from all cardiovascular causes ( 32 percent reduction , P = 0.033 ) . There was no excess of deaths from noncardiovascular causes in the pravastatin group . We observed a 22 percent reduction in the risk of death from any cause in the pravastatin group ( 95 percent confidence interval , 0 to 40 percent ; P = 0.051 ) . CONCLUSIONS Treatment with pravastatin significantly reduced the incidence of myocardial infa rct ion and death from cardiovascular causes without adversely affecting the risk of death from noncardiovascular causes in men with moderate hypercholesterolemia and no history of myocardial infa rct ion Recent large-scale r and omized , controlled trials of 3-hydroxy-3-methylglutaryl coenzyme A ( HMG-CoA ) reductase inhibitors ( statins ) have shown statistically significant reductions in cardiovascular events , strokes , and total mortality among selected groups , including patients with risk factors for vascular disease or a history of vascular disease ( 1 - 5 ) . In addition , cost-effectiveness analyses of the Sc and inavian Simvastatin Survival Study and the West of Scotl and Coronary Prevention Study have shown favorable cost-effectiveness ratios ( 6 , 7 ) . A limitation of the r and omized , controlled trials of statin therapy published to date , however , has been their failure to enroll patients older than 75 years of age . Ongoing r and omized , controlled trials are including patients in this age category , but results will not be available for some time ( 8 , 9 ) . Meanwhile , analyses of data from two secondary prevention trials , the Sc and inavian Simvastatin Survival Study and the Cholesterol and Recurrent Events ( CARE ) trial , have found that participants 65 to 70 years of age and those 65 to 75 years of age , respectively , experienced statistically significant reductions in cardiac end points similar to those seen in trial participants as a whole ( 10 , 11 ) . These results raise the prospect of extending the use of statins to patients older than 75 years of age with established coronary heart disease ( 12 ) . Although the issue of efficacy in patients older than 75 years of age will not be resolved definitively until trials of patients in this age group are published , decision-analytic models can test various assumptions about efficacy to gauge the potential cost-effectiveness of statins in this context . We modeled the cost-effectiveness of statin therapy in a hypothetical cohort of patients 75 to 84 years of age with a history of myocardial infa rct ion by extrapolating results from published r and omized , controlled trials and epidemiologic data . Methods Model We compared two strategies for patients 75 to 84 years of age with previous myocardial infa rct ion : usual care and initiation of HMG-CoA reductase inhibitor therapy . We developed a Markov model ( 13 ) and conducted a cohort simulation to track costs and health outcomes for hypothetical patients r and omly assigned to one of these strategies . In this model , patients can occupy one of six health states : baseline ( history of at least one myocardial infa rct ion ) , recurrent myocardial infa rct ion , postrecurrent myocardial infa rct ion , stroke , post-stroke , or dead ( Figure 1 ) . The model was not configured to deal with multiple events ( such as recurrent myocardial infa rct ion after stroke ) because such sequences of events occur infrequently enough to have a small effect on the overall analysis . Other health states , such as congestive heart failure , were not modeled explicitly but were averaged into the mortality estimates and quality -of-life weights . The model was constructed by using DATA 3.5 software ( TreeAge Software , Williamstown , Massachusetts ) . We adopted the societal perspective in all analyses . Figure 1 . Markov model . MI Transition Probabilities Each state of the model has an associated mortality rate that specifies the probability of dying in any given cycle ( Table 1 ) . These mortality rates were determined by using mortality risk ratios relative to all-cause mortality for an age-matched unselected population ; all-cause mortality rates were obtained from vital statistics data ( 14 ) . We chose to use mortality risk ratios ( multiplicative model ) rather than excess mortality ( additive model ) because a multiplicative model better captures how the risk for death from coronary heart disease changes with age ( 15 , 16 ) . Table 1 . Variables Governing Transition Probabilities for the Markov Model For purpose s of calibration , we initially created a two-state ( alive or dead ) Markov model , with mortality rates based on the 10-year survival curve after acute myocardial infa rct ion for patients 75 to 84 years of age ( 17 ) . The life expectancy of patients in the calibration model was then used as a benchmark to calibrate life expectancy for patients in the usual care strategy of the full six-state model . In the six-state model , we differentiated between death after recurrent myocardial infa rct ion or stroke and death from nonmyocardial infa rct ion or nonstroke causes because statins , by preventing both myocardial infa rct ion and stroke ( 2 ) , also prevent death after these events . Because patients with a history of myocardial infa rct ion have a higher chance of dying of coronary heart disease that is unrelated to recurrent myocardial infa rct ion ( for example , arrhythmia ) , this cohort has a higher risk for death from causes other than myocardial infa rct ion or stroke than does an unselected population . Long-term mortality after recurrent myocardial infa rct ion was adjusted upward to account for the additional risk for death after a recurrent event , on the basis of hazard ratios for coronary heart disease death as a function of nonfatal reinfa rct ion ( 18 ) . We converted these ratios into a hazard ratio for total mortality on the basis of data from the same trial indicating that coronary heart disease caused 76 % of deaths ( 19 ) and on the assumption of no excess risk for noncoronary heart disease death in patients with reinfa rct ion . Mortality rates after stroke were based on published data from the Oxfordshire Community Stroke Project ( 20 ) . Transition probabilities to recurrent myocardial infa rct ion or stroke from the baseline state are based on data describing reinfa rct ion rates ( 21 ) and stroke rates ( 22 , 23 ) . All of the data used to determine transition probabilities are population -based and specific to patients older than 75 years of age , with the exception of data from a clinical trial of patients up to 75 years of age ( 18 , 19 ) . We used data from a follow-up study of patients 65 to 75 years of age in the CARE trial to estimate the relative risk reduction conferred by statin therapy for the end points of myocardial infa rct ion ( fatal and nonfatal combined ) and stroke ( 11 ) . This study stratified patients in the CARE trial into those younger than 65 years of age and those 65 to 75 years of age and found that the latter group experienced statistically significant and clinical ly important reductions in cardiac and cerebrovascular events . Our base-case analysis used the mean estimates of relative risk reduction published in this study for patients 65 to 75 years of age , and the sensitivity analysis used the 95 % confidence limits . We applied risk reductions due to statin therapy to only two transitions out of the baseline state : recurrent myocardial infa rct ion and stroke . Because we did not explicitly model multiple strokes or recurrent myocardial infa rct ion , the model is based on the assumption that patients discontinue statin therapy after their first stroke or recurrent myocardial infa rct ion and no longer experience any additional costs or benefits of statin therapy . We also assumed that patients in the baseline state who are receiving statin therapy continue to accrue the benefits and costs associated with this therapy for the duration of their time in the baseline state . In a sensitivity analysis , we limited benefits of statin therapy to the first 5 years in the baseline state ; this time frame is similar to the duration of follow-up for the large r and omized , controlled trials of statin therapy ( 1 - 5 ) . Under this scenario , after 5 years , patients experience the same event rates and mortality rates as those not using statin therapy but continue to accrue the costs of drug while in the baseline state . This conservative analysis was conducted to examine the consequences of continuing to take a drug that in fact provides no additional benefit beyond the period for which it has been studied . Health-Related Quality of Life The model measured health effects in terms of quality -adjusted life expectancy . The health-related quality -of-life weights for the health states ( Table 2 ) were derived from time-tradeoff scores collected from patients with myocardial infa rct ion in the quality -of-life sub study of Global Use of Strategies to Open Occluded Coronary Arteries ( GUSTO-I ) ( 24 ) , which included patients older than 75 years of age . That study reported quality -of-life scores in patients who experienced various levels of disability from in-hospital stroke after myocardial infa rct ion and in patients who did not have a stroke . The quality -of-life weight ( utility ) for stroke was derived from the mean time-tradeoff utility for patients with ischemic stroke in GUSTO-I because these represent most nonfatal strokes . Bounds for sensitivity analysis were based on quality -of-life estimates approximately 1 SD from the mean . We also conducted a sensitivity analysis in which health states were not adjusted for quality -of-life differences . Table 2 . Utilities , Costs , and Discount Rate The base-case model assumed no disutility associated with statin use . This assumption was based on two studies of pravastatin that included patients older than 75 years of age and showed that pravastatin was well tolerated , with an incidence of adverse events similar to that of placebo ( 25 , 26 ) . However , because we know of no published studies of utilities in patients receiving statins , we performed a sensitivity analysis using a utility decrement of 0.013 in patients taking statins . This number represents the utility decrement related to taking warfarin , a drug associated with considerably more inconvenience ( monthly laboratory monitoring ) , lifestyle modification , and risk than statins ( 27 ) . Costs In the base-case model , we included the following direct medical costs for both strategies : hospitalizations for nonfatal and fatal myocardial infa rct ion , hospitalizations for stroke , and post-stroke institutional care ( nursing home and rehabilitation ) . Patients in the statin group also experienced yearly drug costs and the cost of two additional office visits and two hepatic function Clinical trials have demonstrated a prophylactic role for aspirin in myocardial infa rct ion and in unstable angina pectoris . The Swedish Angina Pectoris Aspirin Trial ( SAPAT ) is the first prospect i ve study of aspirin in stable angina . 2035 patients were r and omised double-blind to treatment with aspirin 75 mg daily or placebo . All patients were treated with sotalol for control of symptoms . The median duration of follow-up was 50 months . Compared with the placebo+sotalol group , the aspirin+sotalol group had a 34 % ( 81 vs 124 patients ) reduction in primary outcome events ( myocardial infa rct ion and sudden death ; 95 % confidence interval 24 - 49 % ; p = 0.003 ) and the reduction observed in secondary outcome events ( vascular events , vascular death , all cause mortality , stroke ) ranged from 22 % to 32 % . Treatment withdrawal caused by adverse events occurred in 109 patients in the aspirin+sotalol group and 100 in patients in the placebo+sotalol group ; major bleeds , including haemorrhagic stroke , occurred in 20 and 13 patients , respectively ( not significant ) . The addition of a low dose of aspirin to sotalol treatment showed significant benefit in terms of cardiovascular events , including a significant reduction in the incidence of first myocardial infa rct ion in patients with symptoms of stable angina pectoris Strategies to reduce deaths from coronary heart disease need to take into account clinical presentation of the disease.1–4 We used a coronary heart register to examine non-fatal and fatal presentations of the disease in a health authority in outer London . Bromley Health Authority employs 151 general practitioners with a total of 295 584 patients on their lists . The Bromley coronary register prospect ively identified all incidences of coronary heart disease in people aged 16–74 from September 1996 to August 1997 for men and from September 1996 to May 1998 for women . The health authority invited general practitioners to refer new cases of suspected exertional angina to a daily “ rapid access ” clinic for patients with chest pain at Bromley BACKGROUND Although numerous clinical trials and economic analyses have established the efficacy and cost-effectiveness of lowering cholesterol for the prevention of coronary heart disease , there are few data on the role of raising high-density lipoprotein cholesterol ( HDL-C ) levels and lowering triglyceride levels . The US Department of Veterans Affairs ( VA ) Cooperative Studies Program HDL-C Intervention Trial ( VA-HIT ) was a multicenter , r and omized trial of gemfibrozil , an agent that raised HDL-C levels and lowered triglyceride levels , yet had no effect on low-density lipoprotein cholesterol ( LDL-C ) levels . The study showed that gemfibrozil therapy significantly reduced major cardiovascular events ( cardiovascular death , myocardial infa rct ion , and stroke ) in patients with coronary heart disease , low HDL-C levels , and low LDL-C levels . OBJECTIVE To report the results of a cost-effectiveness study based on the results of the VA-HIT . METHODS The cost per year of life gained with gemfibrozil therapy was calculated . Hazard functions were estimated , and the result ing probabilities were used in a Markov model simulation to estimate the effect of gemfibrozil on life expectancy and costs over a simulated lifetime . Sensitivity analyses were used to account for uncertainty . RESULTS Using the prices of gemfibrozil that were negotiated by the VA , gemfibrozil was cost saving . Using drug prices found outside the VA , a quality -adjusted life-year saved by gemfibrozil therapy cost between $ 6300 and $ 17 100 . CONCLUSIONS Gemfibrozil reduces major cardiovascular events in male coronary heart disease patients with low levels of HDL-C and low levels of LDL-C and would result in cost saving at annual drug costs of $ 100 or less in 1998 dollars . Even at the higher drug prices represented by the average wholesale price in the United States , the cost of a life-year saved is well below the threshold that would be deemed cost-effective . To our knowledge , this is the first economic analysis based on clinical trial data to assess the cost-effectiveness of raising HDL-C levels and lowering triglyceride levels in a setting in which LDL-C levels were not lowered Three fourths of deaths from myocardial infa rct ion occur in patients older than 65 years of age , making cardiovascular disease the leading cause of death in older persons [ 1 , 2 ] . Older patients , despite their high risk for cardiovascular death , are less likely to receive cardioprotective medications or interventions [ 3 - 15 ] or to be enrolled in clinical trials that test potentially beneficial treatments [ 3 ] . Although much information is available on serum cholesterol as a predictor of coronary artery disease in younger patients , as well as on the benefits of reduction of serum cholesterol levels , the role of cholesterol in coronary artery disease in older patients is less clear . Elevated cholesterol levels do not strongly predict coronary events in older patients [ 16 - 23 ] ; thus , the need for cholesterol screening and treatment in older persons has generated much divergent opinion [ 22 - 31 ] . Recent analysis of a cohort of older persons ( mean age , 80 years ) strongly suggested that concomitant disease or debilitation was associated with low blood cholesterol levels and was responsible for the reduced ability of serum cholesterol levels to predict the incidence of coronary events . After adjustment for low serum iron and albumin levels and exclusion of events in the first year of follow-up , serum cholesterol levels became a significant predictor of coronary death [ 32 ] . Without this adjustment , no such association was seen [ 32 ] . Almost all trials of cholesterol treatment have excluded patients who were 65 years of age or older . The National Cholesterol Education Panel guidelines [ 33 ] therefore extrapolated findings from the treatment of younger patients in their recommendations for treating older patients , noting the considerable potential for absolute risk reduction given the high incidence of cardiovascular events in older patients . More recently , research ers observed that simvastatin treatment of hypercholesterolemic patients with coronary artery disease reduced recurrent major coronary events in the subset of patients who were 65 to 70 years of age at study entry [ 34 ] . However , information is needed on the effect of lipid treatment in older patients who have had myocardial infa rct ion and have average cholesterol levels ; most patients who have had myocardial infa rct ion have cholesterol values in the average , not elevated , range [ 35 - 37 ] . The Cholesterol and Recurrent Events ( CARE ) trial [ 38 ] investigated whether reducing average cholesterol levels by using pravastatin in patients who have had myocardial infa rct ion would prevent recurrent cardiac events . It showed that in patients with average cholesterol levels , pravastatin therapy reduced the risk for coronary death or recurrent myocardial infa rct ion by 24 % ( P = 0.003 ) , reduced the risk for fatal and nonfatal myocardial infa rct ion by 25 % ( P = 0.006 ) , reduced the risk for coronary artery bypass grafting and angioplasty by 27 % ( P < 0.001 ) , and reduced the risk for stroke by 31 % ( P = 0.03 ) [ 38 ] . It also reported that patients who were older than the median age of 59 years had a reduced rate of coronary death , nonfatal myocardial infa rct ion , coronary artery bypass grafting , or percutaneous transluminal coronary angioplasty . Of the 4159 patients in the CARE trial , 1283 ( 31 % ) were 65 to 75 years of age at baseline ; these patients are eligible for retirement health care ( Medicare ) benefits in the United States . We report on the effect of pravastatin on individual cardiovascular events in these older patients , including myocardial infa rct ion , coronary artery bypass grafting , angioplasty , and stroke , as well as on overall hospitalization for cardiovascular disease . Methods Study Design and Patients The design and results of the CARE trial have been described in detail elsewhere [ 38 , 39 ] . The study was a r and omized , double-blind , placebo-controlled trial with a planned average follow-up of 5 years . Patients were recruited from 80 participating centers in the United States and Canada . Institutional review board approval was obtained for investigation of human participants . Patients were eligible if they had had an acute myocardial infa rct ion 3 to 20 months before r and omization ; were 21 to 75 years of age ; and had plasma total cholesterol levels less than 6.2 mmol/L ( 240 mg/dL ) , low-density lipoprotein ( LDL ) cholesterol levels of 3.0 to 4.5 mmol/L ( 115 to 174 mg/dL ) , and fasting triglyceride levels less than 4.0 mmol/L ( 350 mg/dL ) . The diagnosis of myocardial infa rct ion was confirmed by the MI Confirmation Core Laboratory , which evaluated reports of changes in serum creatine kinase levels , electrocardiographic evidence , and clinical symptoms [ 38 , 39 ] . Plasma lipids were measured at least 2 months after discharge from hospitalization for the index myocardial infa rct ion . Women were required to be postmenopausal or surgically sterile . All participants received dietary counseling according to the National Cholesterol Education Program Step 1 guidelines . After the screening visits were completed , eligible patients returned for a r and omization visit , during which they were assigned to receive either pravastatin ( 40 mg/d ) or identically appearing placebo by means of a telephone call from a clinical center to the Data Coordinating Center . The patient was the unit of r and omization , r and omization was stratified within each clinical center , and the allocation schedule was generated by computer . The code for treatment assignment was maintained only at the Data Coordinating Center . The primary trial outcome was fatal coronary artery disease or confirmed nonfatal myocardial infa rct ion . For the primary analysis of the treatment effects in subgroups , we used an exp and ed end point ( death from coronary artery disease , nonfatal myocardial infa rct ion , angioplasty , or coronary artery bypass grafting ) , called major coronary events . Statistical Analysis All analyses were done on an intention-to-treat basis . P values ( all of which were two-sided ) less than 0.05 were deemed statistically significant . Baseline characteristics in the two treatment groups were determined by using the st and ard z-test for continuous variables and chi-square tests for categorical variables [ 40 ] . All hypothesis testing and risk reductions ( with their CIs ) were assessed by using the Cox proportional-hazards model . Kaplan-Meier survival curves for the control and pravastatin groups were calculated [ 41 ] . The relative risk reduction was calculated as 1 the hazard ratio . The upper and lower bounds of the 95 % CIs for the relative risk reductions were applied to the rates in the placebo group to compute the CI for absolute risk reduction , and these bounds were inverted to provide the CIs for the number of patients needed to treat to prevent an event . To determine whether imbalances in risk factors at baseline could have affected the estimates of risk reduction attributable to therapy , we performed subsidiary multivariate analyses that included the following covariates : age , sex , baseline lipid levels , smoking , diabetes , hypertension , and left ventricular ejection fraction . Potential clinical center effects were assessed by including 79 indicator variables to denote the 80 clinical centers in the Cox proportional-hazards analysis . We used SAS software , version 6.12 ( SAS Institute , Cary , North Carolina ) , to execute all analyses . Role of the Study Sponsor The CARE trial was an investigator-initiated study proposed to and funded by Bristol-Myers Squibb . The data were collected and analyzed by and are now maintained at the Coordinating Center , University of Texas School of Public Health . The sponsor is entitled to comment on manuscripts before su bmi ssion . The authors may consider these comments , but the rights to publication reside contractually with the investigators . The sponsor , a member of the Executive Committee of the trial , was contractually required to fund the study until its conclusion . The sponsor maintained information on adverse events and other trial data , as required by federal regulations . Results Screening and Exclusion before R and omization From a total of 11 207 patients identified from records in hospitals and ambulatory practice s for possible inclusion in the CARE trial , 3244 ( 29 % ) were at least 65 years of age ( hereafter referred to as older patients ) . Of these 3244 older patients , 1139 ( 35 % ) qualified for the trial . An additional 144 patients reached the age of 65 years between their screening date and r and omization ; thus , 1283 older patients were r and omly assigned in the CARE trial . A similar percentage of the patients younger than 65 years of age ( hereafter referred to as younger patients ) -39 % ( 3020 patients ) -qualified for the trial . Older patients were less likely than younger patients to be ineligible because of elevated total cholesterol , LDL cholesterol , or triglyceride levels ( 8 % and 12 % , respectively ) . However , older patients were more likely than younger patients to be ineligible because criteria for myocardial infa rct ion were not met ( 61 % and 53 % , respectively ) ( P < 0.05 for all comparisons ) . Baseline Characteristics The median follow-up was 5 years ( 25th and 75th percentiles , 4.3 and 5.4 years ) . The mean age of the older patients was 69 years at r and omization ( 25th and 75th percentiles , 66 and 73 years ) and 74 years at the end of the trial . Baseline coronary risk factors significantly differed between the two age groups ( Table 1 ) . Older patients more frequently were female ( 18 % compared with 12 % of younger patients ) , had hypertension ( 48 % compared with 40 % ) , and had diabetes ( 19 % compared with 12 % ) . In addition , they were more likely to have had a second previous myocardial infa rct ion ( 21 % compared with 15 % ) and less frequently were current smokers ( 12 % compared with 24 % ) , had ever smoked ( 70 % compared with 81 % ) , or had a family history of coronary artery disease ( 33 % compared with 44 % ) ( P < 0.05 for all comparisons ) . Table 1 . Baseline Characteristics of Patients Younger Than 65 Years of Age and Those |
13,898 | 23,048,010 | No class of tocolytic was significantly superior to placebo in reducing neonatal respiratory distress syndrome .
Prostagl and in inhibitors and calcium channel blockers were the tocolytics with the best probability of being ranked in the top three medication classes for the outcomes of 48 hour delay in delivery , respiratory distress syndrome , neonatal mortality , and maternal side effects ( all cause ) .
Conclusions Prostagl and in inhibitors and calcium channel blockers had the highest probability of delaying delivery and improving neonatal and maternal outcomes | Objective To determine the most effective tocolytic agent at delaying delivery . | OBJECTIVES To compare the efficacy and safety of nifedipine and ritodrine in preventing preterm labor , and to evaluate maternal side effects and neonatal outcome . STUDY DESIGN Non-blind , r and omized controlled trial RESULTS A r and omized trial of 102 pregnant women with gestational ages under 34 weeks , including 24 with twin pregnancies and 45 on betasympathicomimetic drugs , who had regular uterine contractions with either observed cervical changes or preterm rupture of membranes . After stratification women were r and omly assigned to receive either ritodrine intravenously or nifedipine orally . Fifty-five women were r and omized to the nifedipine group and 47 to the ritodrine group . As expected , both groups were comparable in terms of several entry variables , including mean gestational age , ruptured membranes , treatment with tocolytic drugs , cervical examination , contraction frequency , age , and twin gestation . Delivery of women in the nifedipine group was delayed for 48 h , 7 days , and until 34 weeks gestation in 33 ( 60 % ) , 26 ( 47 % ) and 21(38 % ) cases , respectively , compared with 31 ( 66 % ) , 21(45 % ) and 11(23 % ) women in the ritodrine group ( no significant difference ) . Maternal side effects were significantly less common in the nifedipine group than in the ritodrine group , however after 7 days of therapy there was no difference between the two groups . Neonatal outcome was similar in the two groups , with four neonatal deaths in the nifedipine and five in the ritodrine group . CONCLUSIONS Nifedipine seems to be as effective as ritodrine in the treatment of preterm labor and is associated with less frequent side effects Ninety-six patients with preterm labor at 28 weeks to 35 weeks gestation were r and omized to terbutaline or magnesium sulfate untill 36 weeks gestation , 25 patients were excluded from the study . Of the remaining 71 patients , 35 patients received terbutaline and 36 patients received magnesium sulfate . The result of the study showed that , there were no significant differences ( P > 0.05 ) regarding time to stop , mean gestational age at delivery , time gained , failure rate , time to recurrent labor and readmission for recurrent labor , birth weight , apgar score and fetal survival . Serious maternal side effects were not observed with terbutaline or magnesium sulfate , although the majority of women also received dexamethasone . Neither drug caused serious adverse neonatal effects PURPOSE to compare the effectiveness of transdermal nitroglycerin with oral nifedipine in the inhibition of preterm delivery . METHODS a clinical essay has been performed with 50 women in preterm delivery , r and omly divided into two groups , 24 receiving oral nifedipine ( 20 mg ) , and 26 , transdermal nitroglycerin ( 10 mg patch ) . Patients with a single gestation , between the 24th and the 34th weeks and diagnosis of preterm delivery were selected . Women with fetal malformation and clinical or obstetric diseases were excluded . The variables analyzed were : effective tocolysis , time needed for tocolysis , recurrence frequency , progression to preterm delivery , and side effects . RESULTS tocolysis efficacy in the first 12 hours was similar between the groups ( nitroglycerin : 84.6 % versus nifedipine : 87.5 % ; p=0.50 ) . The time average time needed for tocolysis was also similar ( 6.6 versus 5.8 hours ; p=0.30 ) . There was no difference between the groups , concerning the recurrence of preterm delivery ( 26.9 versus 16.7 % ; p=0.30 ) , and neither in the rate of preterm delivery within 48 hours ( 15.4 versus 12.5 % ; p=0.50 ) . Nevertheless , the cephalea rate was significantly higher in the Nitroglycerin Group ( 30.8 versus 8.3 % ; p=0.04 ) . CONCLUSIONS transdermal nitroglycerin has presented similar effectiveness to oral nifedipine to inhibit preterm delivery in the first 48 hours , however with higher cephalea frequency OBJECTIVE To compare the effectiveness and adverse effects of nifedipine versus indomethacin in the treatment of preterm labor . METHODS In a r and omized clinical trial , 79 women with labor pain at 26 - 33 weeks of gestation were treated with either oral nifedipine ( n=40 ) or rectal indomethacin ( n=39 ) . RESULTS Twenty-three ( 59 % ) women in the indomethacin group , and 10 ( 25 % ) in the nifedipine group did not respond to treatment ( P=0.002 ) . None of the 16 and 30 women remaining in the indomethacin and nifedipine groups , respectively , delivered during the subsequent 48 hours . Of these remaining women , 1 ( 6.25 % ) in the indomethacin group and 4 ( 13.3 % ) in the nifedipine group delivered between 48 hours and 7 days ( P=0.162 ) . For the women who responded to treatment , the mean gestational age at time of delivery was 238.5±19.4 days and 246.4±15.4 days in the nifedipine and indomethacin groups , respectively ( P=0.182 ) . Seventeen ( 42.5 % ) women in the nifedipine group , and 11 ( 28.2 % ) in the indomethacin group showed adverse effects ( P=0.184 ) . CONCLUSION Indomethacin was less effective than nifedipine for the fast treatment of preterm labor . For women who responded to treatment within 2 hours , however , the delaying of delivery by indomethacin was similar to that by nifedipine 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 OBJECTIVE to establish the efficacy and safety of nifedipine and magnesium sulfate in arresting preterm labor . METHOD seventy-four patients with singleton pregnancies at 23 - 36 weeks in preterm labor , were selected r and omly to receive either oral nifedipine or intravenous magnesium sulfate . RESULTS both drugs had similar tocolytic efficacy and side effects while nifedipine was faster than magnesium sulfate in arresting uterine contractions ( 4.8 + /- 4.23 vs. 2.98 + /- 3.03 h ) P = 0.04 . CONCLUSION this data suggests that oral nifedipine with the same efficacy , side effects and faster action could be a suitable and more convenient alternative to intravenous magnesium sulfate in arresting preterm labor In a multicenter series of r and omized prospect i ve doubleblind controlled studies , ritodrine hydrochloride was compared with either ethanol or placebo in treatment of idiopathic preterm labor . When compared with controls , there was , among offspring of ritodrine-treated mothers , a significantly reduced incidence of neonatal death and respiratory distress syndrome ( P<.05 in both comparisons ) and a significantly higher proportion of infants achieving 36 weeks ' gestation ( P<.05 ) or birth weight greater than 2500 g ( P<.05 ) . There was also a significant improvement in gestational age at delivery ( P<.05 ) and in the number of days gained in utero ( P<.001 ) among ritodrine-treated patients as compared with controls . These results , coupled with a finding of generally acceptable side effects , have contributed to ritodrine 's becoming the first drug approved for the treatment of preterm labor in the United OBJECTIVE This study was undertaken to assess the effectiveness of glyceryl trinitrate ( GTN ) patches in comparison with beta2 sympathomimetics ( beta2 ) for the treatment of preterm labor . STUDY DESIGN A multicenter , multinational , r and omized controlled trial was conducted in tertiary referral teaching hospitals . Women in threatened preterm labor with positive fetal fibronectin or ruptured membranes between 24 and 35 weeks ' gestation were recruited and r and omly assigned to either beta2 or GTN with rescue beta2 tocolysis if moderate-to-strong contractions persisted at 2 hours . Obstetric and neonatal outcomes were assessed . RESULTS Two hundred thirty-eight women were recruited and r and omly assigned , 117 to beta2 and 121 to GTN . On a strict intention-to-treat basis , there was no significant difference in the time to delivery using Kaplan-Meier curves ( P = .451 ) . At 2 hours , 27 % of women receiving beta2 had moderate or stronger contractions compared with 53 % in the GTN group ( P < .001 ) . This led to 35 % of women in the GTN group receiving rescue treatment . If delivery or requirement for beta2 rescue are regarded as treatment failure , then a significant difference was observed between the 2 arms ( P = .0032 ) . There were no significant differences in neonatal outcomes . CONCLUSION GTN is a less efficacious tocolytic compared with ss2 sympathomimetics Objective To compare a new loading dose regimen for intravenous ritodrine administration in preterm labour with the conventional dose regimen The authors compare the efficiency of two drugs in the treatment of threatened premature labour , the one being the calcium inhibitor ( nifedipine ) and the other a beta-mimetic drug ( ritodrine ) . 62 patients after r and om selection were divided into two groups : 32 treated with ritodrine and 30 treated with nifedipine . The treatment was carried out over 7 days . The success rate was similar in both groups -72 % for the ritodrine group and 63.33 % for the nifedipine group . Women receiving nifedipine had slightly greater gain in weeks , six as against five for ritodrine . The side effects which were often found with nifedipine were ; hot flushes ( in 10 cases ) and headaches ( 4 cases ) . These symptoms appeared 15 - 30 minutes after the first dose and were transitory . No neonatal complications were found . The ease with which a calcium inhibitor can be given suggests that it should be used more frequently in the treatment of threatened premature labour and particularly when there are contra-indications to the use of beta-mimetic drugs One hundred six patients in preterm labor with intact amniotic membranes and gestational age less than or equal to 32 weeks were r and omized to receive either ritodrine hydrochloride or a 48-hour course of indomethacin for tocolysis . The relative efficacy , maternal and neonatal safety , and costs were evaluated to determine which may be the more appropriate first-line pharmacologic agent used to manage preterm labor . Fifty-four patients and 52 patients were r and omized to receive ritodrine hydrochloride or indomethacin , respectively . Ritodrine hydrochloride and indomethacin were equally effective in inhibiting uterine contractions and delaying delivery . Delivery was delayed for at least 48 hours in 83 and 94 % , and for at least 7 days in 70 and 75 % of patients receiving ritodrine or indomethacin , respectively . Tocolysis with indomethacin was associated with no maternal side effects , whereas tocolysis with ritodrine hydrochloride was associated with a 24 % incidence of serious cardiovascular and metabolic adverse effects prompting discontinuation of the drug . There were no differences in outcome between the infants exposed to indomethacin versus ritodrine hydrochloride when delivered either remote from therapy or during therapy , except for a statistically higher serum glucose in the infants exposed to ritodrine hydrochloride when delivered during tocolytic therapy . There were no cases of premature closure of the ductus arteriosus or pulmonary hypertension . Tocolysis with indomethacin was 17 times less costly than tocolysis with ritodrine hydrochloride . For gestations less than or equal to 32 weeks complicated by preterm labor , indomethacin may be an appropriate alternative as a first-line tocolytic agent One hundred women in preterm labor were r and omly treated with ritodrine or terbutaline in a double-blind fashion . The drugs were comparably effective during intravenous therapy but , in women with intact membranes , an oral dose of terbutaline , 30 mg daily , was significantly more effective than ritodrine , 120 mg daily , in preventing recurrent labor during a 5-day course of oral therapy ( one of 19 versus 12 of 23 , p less than 0.001 ) . In women with intact membranes , pregnancy was prolonged 40 + /- 25 days ( mean + /- SD ) in women receiving terbutaline orally and only 22 + /- 24 days in women receiving ritodrine orally ( p less than 0.01 ) . In women with intact membranes , a heart rate greater than or equal to 130 bpm occurred in in a higher proportion of women receiving intravenous treatment with ritodrine than among those receiving terbutaline ( 20 of 31 versus 8 of 27 , p less than 0.05 ) . Terbutaline-treated women , however , were significantly more likely to have a serum glucose level in excess of 140 mg/dl than were women treated with ritodrine ( 13 of 26 versus 6 of 29 , p less than 0.05 ) . Side effects commonly observed during intravenous therapy included nausea ( 22 % ) , chest pain ( 15 % ) , and shortness of breath ( 15 % ) . Side effects were significantly ( p less than 0.025 ) more likely to occur during periods when the infusion rate was being increased rather than during periods when the infusion rate was constant OBJECTIVE The purpose of this r and omized study was to evaluate the effects of indomethacin ( 10 patients ) and sulindac ( 10 patients ) given for 4-days on the fetal cardiac function and ductus arteriosus in pregnancies complicated by threatened premature labor between 28 and 32 gestational weeks . STUDY DESIGN By use of pulsed color Doppler techniques the pulsatility index in fetal ductus arteriosus was calculated . Peak systolic velocities in the fetal ascending aorta and pulmonary trunk were also measured . By M-mode echocardiography both ventricular inner end-diastolic and end-systolic diameters were measured and ventricular fractional shortenings were calculated . Tricuspid valve regurgitation was evaluated by pulsed and color Doppler techniques . The ultrasonic examinations were made before and 4 , 24 , 48 , and 72 hours after the start and 24 hours after the end of medication . RESULTS Indomethacin significantly decreased the mean pulsatility index in fetal ductus arteriosus 4 hours after the beginning of medication . This decrease became greater later during medication , and it was associated with a significant increase in both ventricular inner end-diastolic diameters and with a significant decrease in right ventricular fractional shortening . The mean pulsatility index in the fetal ductus arteriosus increased to control values at 24 hours after the end of medication . Sulindac significantly decreased the mean pulsatility index in fetal ductus arteriosus only 24 hours after the beginning of medication . All other mean pulsatility index values did not differ from control values . Other cardiac parameters remained unchanged during sulindac treatment . CONCLUSION Indomethacin has a significant reversible constrictive effect on the fetal ductus arteriosus that is associated with secondary changes , especially in the right ventricle . Sulindac seems to have only a mild and transient constrictive effect on the fetal ductus arteriosus OBJECTIVES To compare the efficacy of nifedipine and ritodrine in prolonging pregnancy beyond 48 h , 1 week and 36.0 weeks and to evaluate maternal side effects and adverse perinatal outcome . STUDY DESIGN Non-blinded , r and omized controlled trial . Eighty patients with singleton pregnancies admitted for preterm labor with intact membranes between 22 and 35 weeks of gestation were included in the study . Preterm labor was defined as the persistence of at least two symptomatic uterine contractions within a 10 min period during 60 min after admission and despite bed rest . RESULTS Forty women received oral nifedipine and forty intravenous ritodrine . Two patients , one from each group , were excluded because of loss to follow-up after discharge . Therefore , 39 women in the nifedipine and the ritodrine groups , respectively , were evaluable for the final analysis . Baseline characteristics were comparable in both groups . The percentage of initial response , the speed of onset of action and the rate of successful treatment within 48 h were significantly better in the ritodrine group . However , prolongation of pregnancy beyond 7 days and 36 weeks of pregnancy was similar with a significantly lower rate of side effects in the nifedipine group . CONCLUSIONS In this small trial , ritodrine provided more effective tocolysis within the first 48 h than nifedipine at the doses used in this study , although with a significantly higher rate of side effects Background . We evaluated the efficacy and safety of ketorolac ( Toradol ) . Methods . In this prospect i ve trial , 88 women in confirmed preterm labor at ≤32 weeks ' gestation were r and omized to receive magnesium sulfate given as an initial 6 g intravenous bolus followed by continuous infusion therapy ( 2 to 6 g/hr ) or intramuscularly administered ketorolac ( 60 mg loading dose ) followed by 30 mg every 6 hours for a maximum of 24 hours . Results . The study groups were similar with respect to age , parity , cervical status , and gestational age on admission . Ketorolac was more rapid ( 2.71 hr ±2.16 ) in the arrest of preterm labor than was magnesium sulfate ( 6.22 hr ± 5.65 ) . No patient required discontinuance of either drug due to adverse effects . There was no difference in the incidence of neonatal complications between the two groups . Conclusion . In gestations with preterm labor at < 32 weeks , ketorolac appears to be an appropriate first-line tocolytic agent OBJECTIVE To investigate the treatment of preterm labor with the beta-adrenergic agonist ritodrine . METHODS 126 women with preterm labor were r and omly assigned to intravenous infusion of ritodrine or magnesium sulfate treatment . Using minimal effective dosage for inhibition of uterine activity , terminating therapy on time , and repeating the i.v . infusion if contraction restarted were the strategy for treatment . RESULTS Ritodrine was significantly more effective both in the treating period for suppression of contraction ( 2.33 + /- 0.63 hr for initiation of inhibiting uterine activity , 9.38 + /- 3.88 days of accumulative treating period ) and prolongation of gestation ( 4.81 + /- 2.83 wks ) than that of the magnesium sulfate ( P < 0.001 , 0.005 and 0.01 respectively ) , and had a term labor of 73.44 % . There was no serious cardiac and pulmonary complications in the ritodrine group . CONCLUSION The present study has shown that ritodrine as a tocolytic agent is highly effective for the management of preterm labor and relative safe for mother and fetus We conducted a r and omized trial comparing bed rest with tocolysis to determine the therapeutic efficacy , safety , and cost-effectiveness of tocolysis for the treatment of preterm labor after membrane rupture . One hundred nine women participated over a 26-month interval . Treatment groups did not differ significantly in terms of gestational age at membrane rupture , gestational age at delivery , birth weight , maternal or fetal infectious morbidity , respiratory distress syndrome , necrotizing enterocolitis , or perinatal mortality . Prolongation of intrauterine time after the onset of uterine contractions was seen in women receiving tocolysis ( 105.2 + /- 157 hours versus 62.1 + /- 77 hours , p = 0.06 ) . This prolongation was not associated with a significant reduction in the total cost per surviving infant ( tocolysis , $ 38,593 + /- $ 40,887 versus bed rest , $ 43,158 + /- $ 37,116 ; p = 0.445 ) . The cost difference was artifactual . The number of very premature infants born ( less than 28 weeks ' gestation ) was unequal in the two groups ( 12 in the bed rest group and 5 in the tocolysis group ) and skewed the results . Before 28 weeks ' gestation tocolysis was associated with a significant increase in intrauterine time after the onset of regular contractions ( p = 0.05 ) . However , there was no identifiable perinatal benefit garnered from the additional 5 days . After 28 weeks there were no significant differences between treatment groups in terms of intrauterine time after the onset of regular contractions and total cost per surviving infant . Because tocolysis does not improve perinatal outcome and can itself be associated with major maternal morbidity , it should be avoided after 28 weeks ' gestation . Before 28 weeks ' gestation tocolysis may greatly increase intrauterine time , but the benefit of this prolongation is not clear OBJECTIVES This study was design ed to evaluate the efficacy and safety of the oxytocin receptor antagonist atosiban in the treatment of preterm labor . STUDY DESIGN A multicenter , double-blind , placebo-controlled trial with tocolytic rescue was design ed . Five hundred thirty-one patients were r and omized to receive , and 501 received , either intravenous atosiban ( n = 246 ) or placebo ( n = 255 ) , followed by subcutaneous maintenance with the assigned agent . St and ard tocolytics as rescue tocolysis were permitted after 1 hour of either placebo or atosiban if preterm labor continued . The primary end point was the time from the start of study drug to delivery or therapeutic failure . Secondary end points were the proportion of patients who remained undelivered and did not receive an alternate tocolytic at 24 hours , 48 hours , and 7 days . RESULTS No significant difference was found in the time from start of treatment to delivery or therapeutic failure between atosiban and placebo ( median , 25.6 days vs 21.0 days , respectively ; P = .6 ) . The percentages of patients remaining undelivered and not requiring an alternate tocolytic at 24 hours , 48 hours , and 7 days were significantly higher in the atosiban group than in the control group ( all P < or = .008 ) . A significant treatment-by-gestational age interaction existed for the 48-hour and 7-day end points . Atosiban was consistently superior to placebo at a gestational age of > or = 28 weeks . Fourteen atosiban-treated patients and 5 placebo-treated patients were r and omized at < 24 weeks ; the incidence of fetal-infant deaths was higher for the atosiban group at < 24 weeks . Maternal-fetal adverse events were similar except for injection-site reactions , which occurred more often with atosiban . CONCLUSIONS In this trial the treatment of patients in preterm labor with atosiban result ed in prolongation of pregnancy for up to 7 days for those at a gestational age > or = 28 weeks , and this occurred with a low rate of maternal-fetal adverse effects . In addition , at a gestational age > or = 28 weeks , the infant morbidity and mortality of atosiban-initiated st and ard care were similar to those with placebo-initiated st and ard care . Given that all patients in this study were eligible for tocolysis and that , in practice , nearly all patients who are eligible for a tocolytic receive one , the benefit of using atosiban is the placebo-like maternal-fetal side effect profile . These observations support the use of this oxytocin receptor antagonist in the treatment of patients in preterm labor with intact membranes . Efficacy and infant outcome data at < 28 weeks are inconclusive OBJECTIVE The object of this study was to compare the fetal effects of sulindac and terbutaline used in the management of preterm labor on the ductus arteriosus , middle cerebral artery , renal artery , umbilical artery , fetal urine production , and amniotic fluid index . STUDY DESIGN In a r and omized , double-blind study 20 patients with preterm labor and no evidence of fetal structural anomalies or intra-amniotic infection received either sulindac ( 200 mg orally every 12 hours for 6 doses ) or terbutaline ( 5 mg orally every 4 hours ) for 72 hours of therapy . All medications were administered from identical blister packs . Opaque glucose base tablets were given at 4-hour intervals in the sulindac treatment arm to mimic the dosing interval in the terbutaline arm of the study . The Doppler pulsatility indices for the ductus arteriosus , middle cerebral artery , renal artery and umbilical artery and also the fetal urinary output were obtained at baseline and 5 , 12 , 24 , 48 , and 72 hours after the medication was started . Doppler data were analyzed within each group with raw data and between groups with the change in pulsatility indices from baseline . Statistical analysis was performed with the Kolmogorov-Smirnov test for normality , repeated measures analysis of variance , Mann-Whitney rank sum test , and Student t test as appropriate . P < .05 ( 2-tailed ) was used to denote statistical significance . RESULTS There were 10 patients in each group , with no difference in gestational age between the 2 groups ( 32.3 vs 31.7 weeks ) . Sulindac was stopped in 2 patients after severe ductal constriction was noted , in 1 at 12 hours and in the other at 24 hours . One patient at 33 weeks ' gestation was delivered because of fetal distress after 46 hours of sulindac therapy . When analyzed across time within groups , the pulsatility index in the ductus arteriosus decreased significantly at 12 and 24 hours in the sulindac group but not the terbutaline group . No significant differences were noted in the middle cerebral artery , umbilical artery , renal artery , or fetal urinary output within either group over time . Significant differences in the change from baseline in pulsatility index of the ductus arteriosus between the sulindac and terbutaline groups were noted at 5 , 12 , 24 , and 48 hours . A similar effect was noted in the change from baseline in pulsatility index of the middle cerebral artery at 48 and 72 hours . There was a significant decrease in the amniotic fluid index in both groups at 24 , 48 , and 72 hours . The amniotic fluid index in the sulindac group was significantly lower than that in the terbutaline group at 48 and 72 hours of therapy . CONCLUSIONS Sulindac constricted the fetal ductus arteriosus , with an effect noted within 5 hours of starting therapy . The constriction , which resolved in all cases within 48 hours of discontinuing therapy , had minimal effects on the pulsatility index of the middle cerebral artery , renal artery , and umbilical artery . Sulindac and terbutaline both result ed in a significant reduction in the amniotic fluid index , with sulindac having a greater effect OBJECTIVE : To compare oral rofecoxib with intravenous magnesium sulfate as a tocolytic . METHODS : This was a r and omized study of patients who were between 22 and 34 weeks of gestation with preterm labor . Patients were r and omly assigned to receive either daily oral rofecoxib ( 50 mg ) or intravenous magnesium sulfate for a maximum of 48 hours . Outcome variables included delay of delivery for 48 hours and the incidence of side effects . Data were analyzed by using the Student t test , Mann – Whitney U test , & khgr;2 test , and repeated- measures analysis of variance . Sample size calculations were based on previous studies of tocolytic efficacy . RESULTS : Two hundred fourteen patients were r and omly assigned ( 105 received rofecoxib and 109 received magnesium sulfate ) . Delivery was delayed for 48 hours in 95 ( 90.4 % ) and 96 ( 88 % ) of the patients in the rofecoxib and magnesium sulfate groups , respectively ( relative risk 0.97 ; 95 % confidence interval 0.89 , 1.06 ) . To show a statistically significant benefit in delay of delivery past 48 hours , a total of 2,686 patients would be required in each group . There was no difference between the groups over the course of the study in cervical dilatation , amniotic fluid index , or cervical length by vaginal ultrasonography . The median hospital days on the original admission were also similar at 2 for both groups ( P = .10 ) . There was a higher reported incidence of maternal side effects in the magnesium sulfate group ( relative risk 1.81 ; 95 % confidence interval 1.07 , 3.06 ) . There was no difference in the incidence of neonatal side effects . CONCLUSION : There was no difference between oral rofecoxib and intravenous magnesium sulfate in arresting preterm labor . LEVEL OF EVIDENCE : The effect of terbutaline , a " selective " beta2-receptor stimulator , was compared with that of placebo in 30 patients in premature labor . Treatment consisted of an intravenous infusion for at least 8 hours , and then of subcutaneous injections four times daily for 3 days together with peroral treatment , which was continued until the end of week 36 of pregnancy . In 12 of 15 terbutaline-treated patients ( 80 per cent ) premature labor was arrested beyond the treatment period , compared with three of 15 in the placebo group ( 20 per cent ) . This difference is statistically significant ( p less than 0.01 ) . No serious side effects were observed . During infusion , there was an increase in maternal heart rate . This was more pronounced in the terbutaline group ( 30 per cent ) than in the placebo group ( 9 per cent ) . There were no adverse effects on blood pressure , but fetal tachycardia was observed more frequently in the terbutaline than in the placebo group . The results suggest that terbutaline is a safe , potent , and well-tolerated inhibitor of premature labor We compared the effects of ritodrine and atosiban treatments on fetal cardiovascular behavior by computerized nonstress test ( c-NST ) analysis . Women diagnosed with preterm labor were r and omized to receive either atosiban or ritodrine . A c-NST was performed at least 12 hours after the last corticosteroid administration . Differences in fetal cardiovascular behavior were evident when treatment was given before 30 weeks ' gestation . Ritodrine induced higher fetal heart rates , lower long-term variation values , and lower low : high-frequency ratios compared with atosiban . Atosiban induced higher gestational ages at delivery and higher birth weights than ritodrine . The mean Apgar scores were similar for atosiban and ritodrine groups at 1 and 5 minutes . No 5-minute Apgar score was < 7 . With respect with atosiban , ritodrine treatment induces tachycardia and a lower variability of fetal heart rate . Such changes could be erroneously interpreted as signal of fetal distress , namely at lower gestational age Background and Objective : Preterm labor ( PTL ) is a common medical problem during pregnancies and is associated with neonatal mortality and morbidity . Beta-adrenergic agonists are among the most commonly used tocolytic agents . The aim of this study was to compare the effectiveness , safety and adverse effects of terbutaline with those of salbutamol in the prolongation of pregnancy beyond 48 hours and until 37 weeks of gestation . Patients and Methods : Two hundred women with PTL were r and omly assigned to receive subcutaneous terbutaline ( 250 μg ) or intravenous salbutamol ( 0.1 mg ) followed by oral terbutaline ( 20 mg/d ) or oral salbutamol ( 24 mg/d ) as maintenance . The efficacy , side effects and complications after 48 hours and until 37 weeks of gestation were analyzed and compared . Results : There was no significant difference between the two groups in success rate within 48 hours ( P= .091 ) . Gestational age at delivery ( P=.031 ) and the number of days for which the gestation was prolonged ( P=.024 ) were significantly higher in those receiving terbutaline . Adverse effects , including tachycardia ( P=.007 ) and anxiety ( P=.006 ) , were experienced more in the salbutamol group . Birth weight was significantly lower in the salbutamol group ( P=.001 ) . Conclusion : Terbutaline provided more effective tocolysis with fewer adverse effects and a better neonatal outcome . However , terbutaline and salbutamol are equally effective in the first 48 hours Background . Several studies have demonstrated the superior tocolytic effectiveness of nifedipine over ritodrine . Only 1 trial conducted a long‐term follow‐up of newborns and found no difference in psychosocial and motor functioning . In a r and omised , multicentre trial , we compared the tocolytic effectiveness of nifedipine and ritodrine and included a long‐term follow‐up of the newborns after 2 years of age . Methods . Patients with imminent preterm labour were r and omised and received either nifedipine or ritodrine . Side‐effects , tocolytic effectiveness and neonatal outcome were studied . Development of the children was studied after the age of 2 years by a parental question naire . Results . Ninety‐three patients were included . Birth was postponed for an average of 4.3 weeks in the ritodrine group and 5.0 weeks in the nifedipine group ( p = 0.4 ) . Patients who received ritodrine experienced significantly more side‐effects compared to patients who received nifedipine ( 29 versus 4 % , p<0.05 ) . No significant differences were found in either group for average birth weight , Apgar scores after 1 min , neonatal intensive care unit ( NICU ) admission and neonatal complications . Parental question naires after 2 years had a response rate of 70 % . Two‐thirds of the children had developed normally in both groups . In both groups , only a few children were severely retarded ( n = 4 ) . No significant differences in development were found between the 2 groups . Conclusions . Both nifedipine and ritodrine proved effective tocolytic drugs , however ritodrine caused significantly more maternal side‐effects . Neonatal outcome and long‐term development after 2 years of age were not significantly different . We favour nifedipine over ritodrine as a tocolytic drug The most commonly used agents for the treatment of preterm labor have been betamimetic drugs or magnesium sulfate . However due to the side effects and limited success of these drugs clinicians have looked for new alternative agents such as nifedipine . This prospect i ve r and omized study was conducted between June 1999 and July 2000 among patients in a Bongkok hospital admitted with preterm labor and gestational age between 28 and 34 completed weeks gestation . Its aim was to compare tocolytic efficacy of nifedipine with the betamimetic drug terbutaline and to assess maternal side effects of high dose nifedipine in pregnant Thai women . Through a computerized r and om number table these patients received either oral nifedipine or intravenous terbutaline . Overall the results showed that nifedipine a dihydropyridine calcium channel blocker is an effective smooth muscle relaxant with low toxicity and teratogenicity . It is noted that nifedipine was a comparable tocolytic agent when compared with terbutaline and it had a similar tocolytic efficacy . Furthermore nifedipine had significantly less maternal side effects than terbutaline . Thus this study demonstrates that nifedipine has a role in the treatment of preterm labor OBJECTIVE The objective of the study was to compare barusiban with placebo in threatened preterm labor . STUDY DESIGN This was a r and omized , double-blind , placebo-controlled , multicenter study . One hundred sixty-three women at 34 - 35 weeks plus 6 days , and with 6 or more contractions of 30 seconds duration during 30 minutes , cervical length 15 mm or less , and cervical dilatation > 1 and < 4 cm were r and omized to a single intravenous bolus of barusiban ( 0.3 , 1 , 3 , or 10 mg ) or placebo . The primary endpoint was percentage of women who did not deliver within 48 hours . RESULTS None of the barusiban doses reduced the number of uterine contractions compared with placebo . There was no significant difference in the percentage of women who did not deliver within 48 hours ( 72 % placebo and 65 - 88 % barusiban groups ; P = .21-.84 ) . Barusiban was not associated with an adverse safety profile in the woman , fetus , neonate , or infant . CONCLUSION An intravenous bolus of barusiban was no more effective than placebo in stopping preterm labor in pregnant women at late gestational age OBJECTIVE To compare the safety and tocolytic efficacy of oral nifedipine with intravenous terbutaline for the management of threatened preterm labor . MATERIAL AND METHOD Pregnant women between 24 and 36 completed weeks of single gestation with preterm labor were r and omized to either oral nifedipine ( n=20 ) or intravenous terbutaline ( n=20 ) treatment . Nifedipine ( immediate released capsule ) 10 mg was crushed and swallowed , 10 mg every 20 minutes was allowed if necessary with a maximum 40 mg in the first hour . After that 20 mg nifedipine every 4 hours was given , up to 72 hours . Terbutaline was initially infused with the rate 10 g/min with an increment 5 microg/min every 10 minutes if required , until 25 microg/min was reached . Once the contractions had stopped for 2 - 6 hours , the patients were switched to subcutaneous injection with 0.25 mg terbutaline every 4 hours for 24 hours . The main safety outcome was the changes in maternal diastolic blood pressure from baseline and 1 hour after starting the treatment ( deltaDBP(1hr ) ) . Secondary outcomes were the efficacy to delay delivery > or = 48 hours and 7 days , the adverse events and the birth outcomes . RESULTS deltaDBP(1hr ) was greater in the terbutaline group than that in the nifedipine group with no statistically significant difference . Hypotension ( defined as BP < or = 90/60 mmHg ) was found in one patient of the nifedipine group and two patients of the terbutaline group . Seventeen and 14 patients in the nifedipine group and 15 and 12 patients in the terbutaline group had delayed delivery > or = 48 hours and 7 days , respectively . Mothers in the nifedipine group experienced fewer side effects than those in the terbutaline group . Maternal heart rate , at I hour after starting the treatment , increased significantly higher in the terbutaline group than in the nifedipine group . Birth outcomes were measured in all nifedipine group patients , but in only 16 of the terbutaline group patients . Six mothers in each group delivered after 37 weeks . Intraventricular hemorrhage ( IVH ) occurred in three babies ( gestational aged 25 , 29 and 37 weeks ) born to mothers treated with terbutaline . In one baby , IVH related to trauma result ed from the delivery procedure . CONCLUSION The safety and efficacy of nifedipine compares with that of terbutaline for treatment of preterm labor Objective To compare the efficacy of tocolysis with specific regimens of nifedipine and ritodrine . Maternal side effects and neonatal outcome also were evaluated In the etiology of premature labor prostagl and ins fulfill a significant role . It is known that indomethacin is a strong inhibitor of prostagl and in synthesis . The effect of indomethacin on premature labor was studied in a prospect i ve r and omized double-blind study in 36 patients . Eighteen patients received indomethacin and eighteen received placebo . 200 - 300 mg of indomethacin was the total dosage in a 24 hours period . The activity of the uterus was monitored with a cardiotocograph . The mean duration of pregnancy and the mean birth weight in indomethacin group ( 36.4 weeks , 2833 g ) were both significantly greater ( p less than 0.001 ) than that in placebo group ( 31.2 weeks , 2028 g ) . In the indomethacin group 3 children weighted less than 2500 g compared with 14 in placebo group . In 15 of 18 indomethacin treated patients ( 83.3 % ) premature labor was arrested after indomethacin treatment compared with 4 of 18 in the placebo group ( 22.2 % ) . The indomethacin group had a mean 1 minute APGAR score of 9.3 + /- 0.2 whereas the placebo group showed a score of 7.8 + /- 0.5 ( p less than 0.01 ) . Three infants died from respiratory distress syndrome ; one in the indomethacin group ( 1810 g ) and two in the placebo group ( 600 and 1450 g ) . Autopsies in the infants demonstrated a typical picture of pulmonary atelectasis and hyaline membranes . There was no evidence of premature closure of the ductus arteriosus or pulmonary hypertension . 2 mothers in the indomethacin group suffered minor discomfort i.e. nausea , vomiting and vertigo . ( ABSTRACT TRUNCATED AT 250 WORDS AIM The aim of this study was to compare the efficacy and tolerability of atosiban vs ritodrine administered as single-drug or as combination therapy with the COX inhibitor ketoprofen in the treatment of preterm labor and to investigate how frequent is the need for combination therapy with ketoprofen . METHODS Ninety-one women with diagnosis of threatened preterm delivery at 24 - 33 weeks ' gestation were enrolled in an observational case-control study . Forty-seven received IV atosiban ( 6.75 mg initial dose , 300 microg/min loading dose for 3 hours , 100 microg/min maintenance dose for 48 - 96 hours ) and 44 IV ritodrine ( 0.05 - 0.3 mg/min ) . When response to the first drug in the first 2 - 4 hours was unsatisfactory , ketoprofen was added ( 100 mg loading dose IV and 100 - 150 mg maintenance dose every 12 hours ) for a maximum of 48 hours . RESULTS Ketoprofen was added in 51.1 % of the atosiban group and 47.7 % of the ritodrine group ( P 0.75 , not statistically significant ) . The percentages of women non delivered in the two groups were 85.1 % vs 81.8 % at 48 hours ( P=0.44 ) and 59.6 % vs 54.5 % at 7 days ( P=0.39 ) . One woman treated with atosiban reported transient dyspnea at the administration of the bolus dose ; 20.5 % of women who received ritodrine developed tachycardia and 4.5 % dyspnea ( P=0.001 ) . Neonatal mortality and morbidity were comparable in both groups and unrelated to ketoprofen exposure . CONCLUSION Atosiban efficacy was comparable to ritodrine , but with a superior safety profile . A large proportion of women in both groups required second-line ketoprofen therapy , with comparable neonatal outcomes OBJECTIVE The purpose of this study was to establish whether nimesulide causes fewer fetal side effects than indomethacin or sulindac after short-term maternal exposure for tocolysis . STUDY DESIGN This was a double-blind , double-dummy prospect i ve r and omized study with three drug treatment groups ( n = 10 per group ) that were comprised of subjects who were at 28 to 32 weeks of gestation with preterm contractions . The subjects were treated in the delivery suites of two busy inner-city teaching hospitals ; the intervention consisted of 48 hours of treatment and with 72 hours of follow-up observation with indomethacin 100 mg ( twice daily ) , sulindac 200 mg ( twice daily ) , or nimesulide 200 mg ( twice daily ) . The amniotic fluid index , hourly fetal urine production , and ductal Doppler pulsatility index observations were monitored before the treatment and at 4 , 24 , 48 , 72 , and 120 hours after the treatment was started . The statistical analysis used repeated measures analysis of variance , Bonferroni test , and Bl and -Altman agreement . Significance assumed when the probability value was < .05 . RESULTS Each drug caused a significant reduction in all three observations over the 48-hour treatment period , which recovered to pretreatment levels by 72 hours after treatment . There were no significant differences among drugs for any of these effects . CONCLUSION Nimesulide causes similar short-term fetal side effects to indomethacin and sulindac A r and omized prospect i ve trial was performed to compare the efficacy and safety of ritodrine and indomethacin in the long-term treatment of preterm labor . Forty patients with intact membranes in preterm labor at 23 to 34 weeks ' gestation were r and omized to receive either intravenous ritodrine or oral indomethacin as the first-line tocolytic agent . Successful intravenous ritodrine therapy was followed by oral terbutaline therapy , and indomethacin-treated patients continued to receive oral indomethacin . Treatment failures were defined as progressive preterm labor or patient intolerance , and these patients were treated with intravenous magnesium sulfate . Ritodrine and indomethacin were equally successful in delaying preterm birth as defined by interval to delivery , gestational age at delivery , delivery delayed greater than 7 days , attainment of 35 weeks of gestation , percentage of patients who required magnesium sulfate therapy , percentage of patients who were readmitted with premature rupture of membranes , absence of recurrent preterm labor , and infant birth weight . More than 80 % of mothers who received ritodrine voiced complaints of beta-sympathomimetic side effects , and one patient discontinued treatment as the result of intolerance . There were minimal patient complaints with indomethacin use . No statistically significant differences were noted in neonatal outcome as defined by Apgar scores , umbilical cord pH , intensive care days , ventilator days , or neonatal deaths . However , three cases of primary pulmonary hypertension were observed in the indomethacin group . We had not previously observed this problem with short-term ( 24 to 48 hours ) indomethacin therapy Ritodrine as the first-line drug in the treatment of established preterm labor has been supplanted in some centers by magnesium sulfate . To assess the relative efficacy and rates of side effects of these two agents , 120 patients were r and omly assigned to receive one of these two drugs . Patients were included if they had intact membranes and met strict criteria for the definition of labor . In both groups excellent outcome was achieved , with 96.3 % and 92.3 % of patients receiving ritodrine and magnesium sulfate , respectively , obtaining a delay in delivery of greater than 48 hours . Side effects were comparable in both groups , although they tended to be more serious in the patients receiving ritodrine . In patients receiving both drugs together , the rate of side effects was 77 % without a demonstrable benefit over a single agent . We conclude that ritodrine and magnesium sulfate are tocolytics of comparable efficacy and when used aggressively are highly successful in delaying delivery Reported are 1-year follow-up results of a r and omized clinical trial comparing three strategies of managing clinical ly significant patent ductus arteriosus at the time of diagnosis in premature infants : ( 1 ) immediate administration of a three-dose course of intravenously administered indomethacin in addition to usual medical therapy ( fluid restriction and use of diuretics or digitalis or both ) , with surgery as a backup measure , ( 2 ) usual medical therapy alone initially , with indomethacin as the first and surgery as the final backup measure , and ( 3 ) usual medical therapy alone initially , with surgery alone as backup . Of primary concern were the relative merits of these three managements strategies in the terms of the long-term occurrence of a wide range of health problems . Although at the time of neonatal hospitalization there was a significant excess of bleeding episodes in infants receiving indomethacin as part of initial treatment , and a significantly higher rate of retrolental fibroplasia in the those given usual medical therapy with surgery as backup , there were no statistically significant differences at 1 year of age related to these intermediate outcomes . In other regards , too , the treatment strategies appeared interchangeable in terms of the 1-year outcome OBJECTIVE To compare the tocolytic action and the side effects of nicardipine to those of salbutamol in patients presenting premature labor in order to propose nicardipine as a promising alternative to salbutamol in the treatment of premature labor . STUDY DESIGN Ninety patients admitted to the Saint-Antoine Hospital ( Paris , France ) for premature labor were included in this prospect i ve r and omized open study comparing nicardipine and salbutamol . Each study group included 45 patients . RESULTS The mean term of delivery in the nicardipine group was 38.4 + /- 1.7 and 37.6 + /- 2.1 weeks in the salbutamol group ( P < 0.05 ) . The percentage of deliveries after 37 gestational weeks was higher with nicardipine ( P < 0.05 ) . The birthweight of infants was 3131 + /- 488 g with patients treated with nicardipine and 3019 + /- 494 g with the salbutamol group ( NS ) . The Apgar scores were identical in the two groups at 1 and 5 min . There was no statistically significant difference in the number of neonates admitted into intensive care nor the premature infant center between the two groups . Nicardipine reduced the systolic and diastolic blood pressure whereas there was no change in the salbutamol group . Maternal pulse rate was significantly increased in the salbutamol group ( P < 0.01 ) and was unchanged in the nicardipine group . The most common side-effects with nicardipine were headaches , and with salbutamol , tremors and palpitations . CONCLUSIONS Nicardipine is a tocolytic agent as effective as salbutamol in the treatment of premature labor . The use of nicardipine is an interesting alternative to salbutamol , especially in cases of hypertension , diabetes or maternal cardiopathy We compared two dose regimens of tocolytic oral nifedipine . Women with singleton pregnancies admitted in preterm labor ( 24 to 34 weeks ) were r and omized to high-dose ( HD ) nifedipine ( N = 49 ; 20 mg loading dose , repeated in 30 minutes , daily 120 to 160 mg slow-release nifedipine for 48 hours followed by 80 to 120 mg daily until 36 weeks ) or low-dose ( LD ) nifedipine ( N = 53 ; 10 mg , up to four doses every 15 minutes , daily 60 to 80 mg slow-release nifedipine for 48 hours followed by 60 mg daily until 36 weeks ) . Uterine quiescence at 48 hours ( primary outcome ) ; delivery at 48 hours , 34 and 37 weeks ; and recurrent preterm labor were similar . Gestational age at delivery was higher in HD ( 36.0 + /- 2.8 versus 34.7 + /- 3.7 weeks , P = 0.049 ) . Rescue treatment was needed more in LD ( 24.5 versus 50.9 % , odds ratio = 0.3 ; 95 % confidence interval 0.1 to 0.7 ) . Maternal adverse effects , birth weight , intensive care nursery admission , and composite neonatal morbidity were similar . However , neonatal mechanical ventilation was needed less and nursery stay was shorter in HD . HD nifedipine does not seem to have an advantage over LD in achieving uterine quiescence at 48 hours . Further studies should address the optimal dose and formulation of tocolytic nifedipine Preterm labour and delivery remains a major cause of perinatal morbidity and mortality . Numerous drugs and interventions have been used to prevent and inhibit preterm labour but none have been found to be completely effective with the choice being further limited by troublesome side effects . This study compares in a prospect i ve and r and omised design the efficacy and safety of the calcium antagonist Nifedipine with the beta mimetic Isoxsuprine . 81.25 % of patients receiving Nifedipine and 70 % of those receiving Isoxsuprine achieved successful tocolysis . The mean prolongation of pregnancy with Nifedipine was 25+/-19.85 days and with Isoxsuprine it was 19.18+/-17.82 days . Maternal side effects were similar in both groups with hypotension and tachycardia being the commonest . Discontinuation rates were also similar with pulmonary oedema and severe hypotension being the reasons for foregoing tocolysis . It can be concluded that Nifedipine is a safe and effective alternative to Isoxsuprine for suppressing preterm labour We compared the tocolytic effect of indomethacin and nylidrin in a prospect i ve double-blind trial in which the appearance of the tocolytic treatment ( always intravenous infusion and rectal suppositories/oral capsules ) was identical to the subjects . Sixty healthy women in imminent preterm labor between 25 - 34 weeks of singleton gestation were included . Thirty of these women received indomethacin ( concomitantly with placebo infusion ) , with doses as follows : day 1 , 100-mg rectal suppository followed by two oral capsules ( 50 mg ) at 8-hour intervals ; days 2 and 3 , three 50-mg oral capsules each day . Thirty women received intravenous nylidrin ( concomitantly with rectal/oral placebo ) , initiated with the dose of 50 µg/minute and continued at the dose of 100 - 150 µg/minute for a maximum of 3 days . Preterm labor was arrested for 24 , 48 , and 72 hours in 100 , 96 , and 90 % , respectively , of subjects in the indomethacin group , compared with 100 , 76 , and 73 % of women in the nylidrin group ; the difference was significant ( P<.05 ) at 48 hours . Women progressed beyond 37 gestational weeks more commonly ( P<.05 ) with indomethacin ( 21 of 30 , 70 % ) than with nylidrin ( 13 of 30 , 43 % ) . Indomethacin treatment was accompanied by maternal side effects 20 % of the time , significantly less commonly ( P<.001 ) than with nylidrin ( 83 % ) . The neonatal outcome was similar in the two study groups . We conclude from this double-dummy technique trial that indomethacin is more effective and better tolerated than nylidrin in arresting imminent preterm labor OBJECTIVE The purpose of this study was to determine whether intravenous magnesium sulfate ( MgSO4 ) followed by oral nifidepine tocolysis in women with preterm labor between 32 0/7 and 34 6/7 weeks ' gestation reduces neonatal hospital stay . STUDY DESIGN Fifty-four women between 32 0/7 and 34 6/7 weeks with preterm labor were r and omized to receive either MgSO4 and oral nifidepine ( n = 24 ) or no tocolysis ( n = 30 ) . All women received betamethasone and prophylactic antibiotics . The primary outcome was total neonatal hospital stay . Data were analyzed using Chi-square and Mann Whitney U test . RESULTS The 2 groups had similar mean cervical dilation and gestational age at enrollment . There were no statistically significant differences in total neonatal hospital stay ( 5.8 + /- 7.2 days ; median of 3 days in the no tocolysis vs. 7.5 + /- 8.6 days ; median of 3 days in the tocolysis group ) , rate of preterm delivery ( 57 % vs. 75 % ) or need for oxygen supplementation ( 7 % vs. 21 % , p < 0.23 ) . The neonatal complications were similar in each group . CONCLUSION Tocolysis after 32 weeks gestation does not reduce neonatal hospital stay OBJECTIVE The purpose of this study was to test the hypothesis that infusion of the oxytocin antagonist atosiban results in decreased preterm uterine activity in the human . STUDY DESIGN A r and omized , double-blind , placebo-controlled trial was performed . One hundred twenty women from 20 to 36 weeks ' gestation with a complaint of labor who had more than four uterine contractions per hour after intravenous hydration but no evidence of cervical changes were r and omized to receive a 2-hour intravenous infusion of atosiban at a rate of 300 micrograms/min or placebo . Ond hundred-twelve subjects ( 56 in each arm ) were suitable for analysis of efficacy . Both groups remained at bed rest and received hydration . RESULTS The mean percent decrease in contraction frequency was greater in atosiban subjects compared with controls ( 55.3 % + /- 36.3 % vs 26.7 % + /- 40.4 % , mean + /- SD , p < 0.001 ) . A minimal ( < 20 % ) decrease or an increase in contraction frequency was noted in 25 placebo subjects ( 45 % ) and seven atosiban subjects ( 13 % ) . There was no clinical ly or statistically significant change in maternal blood pressure or heart rate during the infusion . The only adverse experiences possibly related to the drug were nausea and vomiting in one atosiban patient . CONCLUSION A 2-hour infusion of the oxytocin antagonist atosiban result ed in a significantly greater decline in contraction frequency compared with controls . Oxytocin appears to play a role in the maintenance of preterm uterine activity in the human Objective : To compare the tocolytic efficacy and side effects of parenteral and oral magnesium and terbutaline . Methods : Ninety-eight patients in labor between 23 - 35 weeks were prospect ively entered into a controlled trial of intravenous and oral magnesium versus subcutaneous and oral terbutaline . Tocolytic effectiveness was judged by delay of delivery for 48 hours or 1 week , and to 37 weeks or more . The need to change therapy to the alternate drug was identified , as were side effects . Entrance characteristics of the population , initial pelvic examination , and concomitant infection or cervicovaginal isolates were noted . Outcomes included gestational age at delivery , birth weights , and Apgar scores . Outcome analysis was based on initial tocolytic therapy . Results : Significantly more patients in the magnesium group delivered at 37 weeks or more : 34 of 46 versus 27 of 52 ( P<.05 ) . No significant differences were found for delivery by 48 hours or 1 week . The interval between treatment and delivery was greater for magnesium : 7.1 ± 3.9 versus 5.0 ± 3.2 weeks ( P<.005 ) . Failure to achieve 37 completed weeks was more often due to obstetric complications than to preterm labor itself . Tocolytic effectiveness was reduced if secondary therapy or re-treatment was required or if the patient had cervical dilatation of 3 cm or greater . Infectious complications were common but were not associated with tocolytic effectiveness . Side effects were more noticeable with oral magnesium and subcutaneous terbutaline . Conclusions : For short-term tocolysis , no significant difference was found between magnesium and terbutaline . Magnesium was associated with a higher term delivery rate . Idiopathic preterm labor accounted for only a small part of the overall prematurity in the study population In a r and omized trial , three alternative schemes of treatment of preterm labour with ritodrine ( long infusion , short infusion , and intramuscular injection ) were compared with st and ard treatment by bed rest and sedatives . None of the ritodrine treatments were found to be better in postponing delivery than the st and ard treatment . However , the Bishop scores of the patients in the st and ard treatment group tended to be lower than of the patients treated with ritodrine . Moreover , all cases of congenital malformation and polyhydramnios occurred in the patients treated with ritodrine . The incidence of respiratory insufficiency was significantly higher in infants of mothers treated with ritodrine . The mean birth weight was highest in the st and ard treatment group To observe the efficacy of magnesium sulfate in the treatment of preterm labor , 65 uncomplicated cases of preterm labor between 28 and 36 weeks of gestation were studied prospect ively during Sep. 1988-May 1991 . They were divided into two groups r and omly . 30 cases were treated with magnesium sulfate and 35 cases with barbiturates or bed rest . The prevention of delivery for at least 48 hours after the initiation of therapy was achieved in 23 of the 30 cases ( 76.67 % ) of the magnesium sulfate group and in 3 of the 35 cases ( 8.57 % ) in the control group . Delay of more than 7 days was achieved in 17 of the 30 cases ( 56.67 % ) and in 2 of the 35 cases ( 5.71 % ) . The postponement of delivery between the two groups . There was highly significantly difference ( P less than 0.01 ) . There was a significant correlation of cervical dilation at the onset of treatment to success of controlling preterm labor . In the magnesium sulfate group , the mean magnesium level to achieve tocolysis was 2.8 + /- 0.35 mmol/L ( mean + /- s ) . The side effects to the mothers , fetus , and the neonates were mild and not prominent . ( ABSTRACT TRUNCATED AT 250 WORDS In India the rate of preterm birth is high ( 9.5 % ) . Adequate neonatal intensive care facilities are available but fairly skewed in their location . Various agents and different routes have been tried for the management of preterm labor . This study was conducted over a period of one year in a teaching hospital in Surat India to evaluate the safety and efficacy profile of nifedipine and ritodrine in the management of preterm labor . A r and omized non-controlled trial design was used . Seventy consecutive women with symptoms of preterm labor and fulfilling design ated inclusion criteria were recruited with 35 women ( odd numbers ) being allocated to ritodrine group and 35 ( even numbers ) to nifedipine group . Informed consent was taken and the study was approved by the Hospital Ethics Committee . In group A women received intravenous ritodrine followed by oral ritodrine for 72 h. In group B nifedipine was administered orally for 72 h. Subjects with less than 34 weeks gestation received injection betamethasone 12 mg in 2 doses 12 h apart . Uterine activity cessation and maternal side effects were noted . The dosage schedules for nifedipine and ritodrine were based on the recommendations of King et al. and Arias et al. respectively . ( excerpt The efficacy of magnesium sulfate was analyzed in relation to ritodrine hydrochloride . Patients presenting in preterm labor between 20 and 35 weeks ' gestation were prospect ively r and omized . Tocolysis was achieved for more than 72 hours in 35 of 40 cases ( 88 % ) where magnesium sulfate was administered and 31 of 39 cases ( 79 % ) in which ritodrine hydrochloride was infused . Delay of greater than or equal to 7 days was achieved in 75 % and 72 % of cases , respectively . The mean dosage to achieve tocolysis was 4.5 gm/hr , in the magnesium sulfate group and 210.0 micrograms/hr in ritodrine hydrochloride-treated patients . The mean magnesium level to achieve tocolysis was 6.60 mg/dl . Side effects in the two groups were similar in number but less alarming in the magnesium sulfate group . Magnesium sulfate was found to be easy to administer and clinical ly efficacious . Its tocolytic action was found to be dose dependent and drug concentrations are easily determined . On the basis of this work and data from other investigators , magnesium sulfate should be used as the first line of tocolytic therapy with ritodrine hydrochloride as its pharmacologic backup 140 patients with a threatening premature birth at the greater than or equal to 24-less than 37 week of gestation were in this study r and omly treated with hexoprenalin or salbutamol . In 77 % in the hexoprenalin and in 74 % in the salbutamol group the weight of the newborn was greater than or equal to 2500 g. In 66 % in both study groups the birth occurred after the completed 37 weeks of gestation . During infusion of hexoprenalin tachycardia in mothers occurred statistically highly significantly less than during salbutamol . 11 % of the mothers in the hexoprenalin group had side-effects during infusion compared to 30 % in the salbutamol group . The correlation between the tocolysis-index ( Baumgarten ) and the prolongation-index ( Richter ) given by the regression lines facilitates in some measure the comparison of different tocolytic drugs concerning its tocolytic effect OBJECTIVE The aim of this study was to compare the efficacy and safety of oral nicardipine in acute therapy for preterm labor with those of parenteral magnesium sulfate . STUDY DESIGN Patients between 24 and 34 weeks ' gestation with documented preterm labor were r and omly assigned to receive oral nicardipine ( n = 57 ) or intravenous magnesium sulfate ( n = 65 ) as initial tocolytic therapy . Patients in the nicardipine group received a 40-mg loading dose and then 20 mg every 2 hours as needed to stop contractions ( total 80 mg ) . Patients in the magnesium sulfate group received a 6-g bolus followed by 2 to 4 g/h to provide uterine quiescence . Patients could be switched to another tocolytic regimen if they continued to have contractions after 6 hours of therapy . The main outcome variables examined were time to uterine quiescence , time gained in utero , recurrence of preterm labor , failure of tocolysis , and pertinent maternal and neonatal outcomes . RESULTS There were no significant differences in maternal demographic characteristics between the groups . Among patients who responded with uterine quiescence within 6 hours , there was a significant decrease in the time to uterine quiescence in the nicardipine group ( P < .01 ) . Patients in the magnesium sulfate group were more likely to have recurrence of preterm labor necessitating further tocolytic attempts ( P = .048 ) . The patients in the magnesium sulfate group had more adverse side effects , mainly nausea and vomiting ( P = .004 ) . There were no differences in birth weight , estimated gestational age at delivery , or neonatal complications between the 2 groups . CONCLUSIONS Oral nicardipine is an effective , safe , and well-tolerated tocolytic agent . In this prospect i ve clinical trial patients r and omly assigned to receive oral nicardipine had arrest of preterm labor more rapidly than did those r and omly assigned to receive parenteral magnesium sulfate . Patients who received magnesium sulfate were more likely to have adverse medication effects and recurrent preterm labor One hundred fifty-six women with preterm labor between 24 and 34 weeks ' gestation were r and omized to receive either intravenous magnesium sulfate or no tocolytic therapy . Magnesuim sulfate infusions of up to 3 gm/hr were used in 76 pregnancies and result ed in a mean serum magnesium concentration of 5.5 + /- 1.4 mEq/L ( mean + /- SEM ) . Compared with 80 control pregnancies , magnesium sulfate tocolysis had no significant effect on duration of gestation , birth weight , neonatal morbidity , and perinatal mortality . We conclude that clinical ly safe infusions of magnesium sulfate are ineffective when used to prevent preterm birth In travenous magnesium sulfate and alcohol were compared as treatments for premature labor . A successful treatment was the absence of contractions for a 24 hour interval . Early treatment was found to be essential for successful management of premature labor . There is a significant correlation of cervical dilatation at the onset of treatment to success at controlling premature labor . There was no statistically significant relation to weeks of gestation or parity to success at controlling premature labor . In this study magnesium sulfate was the better agent for controlling premature labor A r and omized controlled study was carried out at three medical centers to compare the efficacy and side effects of ethanol and ritodrine in the treatment of threatened premature labor . One hundred and thirty-five patients judged to be between the twentieth and thirty-sixth week of gestation and presenting with clinical symptoms of premature labor were included . Sixty-seven patients were treated with intravenous infusion of 10 per cent ethanol . Sixty-eight patients were treated with intravenous infusion of ritodrine for 12 hours followed by oral ritodrine . If labor recurred prematurely , up to two additional courses of ethanol or ritodrine were given . Delivery was postponed for more than 72 hours in 49 of 67 patients ( 73 per cent ) with ethanol and in 61 of 68 patients ( 90 per cent ) with ritodrine ; this difference was significant . Patients in the ethanol group gained a mean of 27.6 days while patients in the ritodrine group gained a mean of 44.0 days . Fifty-four per cent of the ethanol group and 72 per cent of the ritodrine group carried their infants to 36 weeks of gestation . Five infants in the ethanol group and one infant in the ritodrine group died from respiratory distress syndrome . The most frequent side effect of ethanol were nausea and vomiting . The most frequent side effects of ritodrine were tachycardia and blood pressure changes which were easily controlled by lowering the infusion rate . Ethanol and ritodrine were both found to be effective inhibitors of premature labor with ritodrine giving the most favorable results BACKGROUND / PURPOSE Management of preterm labor involves the use of tocolytic drugs to inhibit preterm uterine contractions . This study compared the efficacy and safety of intravenous administration of atosiban and ritodrine in the treatment of spontaneous preterm labor . METHODS A r and omized study was conducted in pregnant women of Chinese origin in Taiwan with threatened preterm delivery . Patients were r and omized to receive either atosiban ( n = 23 ) or ritodrine ( n = 22 ) . Tocolytic efficacy of the drug was assessed as the proportion of women who did not deliver and did not need alternative tocolytic treatment at 7 days after therapy initiation . Safety of the drugs was assessed as the number of adverse events or neonatal morbidity . RESULTS The number of women who did not deliver and did not require alternative tocolytic therapy at 7 days was similar between the atosiban and ritodrine groups . There were no serious adverse events , but maternal cardiovascular adverse events , particularly tachycardia , occurred significantly more in women treated with ritodrine ( 0 % atosiban vs. 18.18 % ritodrine , p < 0.05 ) . There was no difference in neonatal or infant outcome between the two drugs . CONCLUSION The present study showed similar effectiveness between atosiban and ritodrine , while tachycardia occurred more frequently in women treated with ritodrine . These results indicate that atosiban is an effective tocolytic drug without the conventional cardiovascular side effects often seen with beta-agonist treatment OBJECTIVE This study was undertaken to compare the efficacy and safety of intravenous administration of atosiban versus ritodrine for the treatment of preterm labor . STUDY DESIGN Women with preterm labor and intact membranes diagnosed at 23 to 33 gestational weeks ( n = 247 ) were r and omly assigned to treatment arms and received atosiban ( 6.75 mg intravenous bolus , 300 microg/min for 3 hours , then 100 microg/min intravenously ) or ritodrine ( 0.10 - 0.35 mg/min intravenously ) for as long as 18 hours . Tocolytic effectiveness was assessed in terms of the numbers of women who had not been delivered after 48 hours and after 7 days . Safety was assessed in terms of maternal side effects and neonatal morbidity . Secondary outcomes included mean gestational age at delivery and mean birth weight . An intent-to-treat analysis was performed with the Cochran-Mantel-Haenszel test . RESULTS The proportion of women who had not been delivered at 48 hours was 84.9 % ( n = 107 ) in the atosiban group and 86.8 % ( n = 105 ) in the ritodrine group . At 7 days 92 women had still not been delivered in both the atosiban ( 73.0 % ) and ritodrine ( 76.0 % ) groups . Neither of these differences was statistically significant . The incidence of maternal cardiovascular side effects was substantially lower in the atosiban group ( 4.0 % vs 84.3 % , P < .001 ) . In addition , intravenous therapy was terminated more frequently as a result of maternal adverse events in the ritodrine group ( 29.8 % ) than in the atosiban group ( 0.8 % ) . The overall occurrences of fetal adverse events in the two treatment groups were comparable . Neonatal morbidity was similar between the treatment groups after adjustment for unbalanced enrollment of women with multiple pregnancies and for gestational ages within treatment groups . CONCLUSION Atosiban was comparable in clinical effectiveness to conventional ritodrine therapy but was better tolerated than ritodrine , with no evidence of significant maternal or fetal adverse events . Neonatal morbidity , which was similar between the two treatment arms , was apparently related to the gestational age of the infant rather than to the exposure to either tocolytic agent Summary . The efficacy of an orally administered calcium antagonist , nifedipine , in suppressing premature uterine activity , was compared with intravenous ritodrine and no treatment . Nifedipine was found to be significantly more effective than ritodrine or withholding therapy , and was almost devoid of side‐effects Objective To compare the efficacy of nifedipine with ritodrine in the management of preterm labor . Methods One hundred eighty-five singleton pregnancies with preterm labor were assigned r and omly to either ritodrine intravenously ( n = 90 ) or nifedipine orally ( n = 95 ) . The principal outcome assessed was delay of delivery . Results Ritodrine was discontinued in 12 patients because of severe maternal side effects , and their results were excluded from further analysis . More women in the ritodrine group delivered within 24 hours ( 22 versus 11 , P = .006 ) , within 48 hours ( 29 versus 21 , P = .03 ) , within 1 week ( 45 versus 36 , P = .009 ) , and within 2 weeks ( 52 versus 43 , P = .005 ) compared with those receiving nifedipine . There were significantly fewer maternal side effects in the nifedipine group . Apgar scores and umbilical artery and vein pHs were similar in both groups . The number of admissions to the neonatal intensive care unit ( NICU ) in the nifedipine group was significantly lower than in the ritodrine group ( 68.4 versus 82.1 % , P = .04 ) . Conclusion Nifedipine in comparison with ritodrine in the management of preterm labor is significantly associated with a longer postponement of delivery , fewer maternal side effects , and fewer admissions to the NICU Women at risk of premature delivery were divided r and omly into 2 groups of 80 each . Mefenamic acid 500 mg 3 times a day or a placebo was given in a double blind fashion . Preterm delivery occurred in 15 % of the treated group and 40 % of the control group ( p < 0.005 ) . The mean birth weight in the test group was higher as compared to the controls . There were no cases of foetal malformations in either of the groups . The results support the use of Mefenamic acid in preventing premature labour OBJECTIVE To compare the safety and efficacy of high-dose intravenous ( IV ) nitroglycerin with those of IV magnesium sulfate for acute tocolysis of preterm labor . METHODS Thirty-one women with preterm labor before 35 weeks ' gestation were assigned r and omly to IV magnesium sulfate or IV nitroglycerin for tocolysis . Preterm labor was defined as the occurrence of at least two contractions in 10 minutes , with cervical change or ruptured membranes . Acute tocolysis was defined as tocolysis for up to 48 hours . Magnesium sulfate was administered as a 4-g bolus , then at a rate of 2 - 4 g/h . Nitroglycerin was administered as a 100-microg bolus , then at a rate of 1- to 10-microg/kg/min . The primary outcome measure was achievement of at least 12 hours of successful tocolysis . RESULTS Thirty patients were available for analysis . There were no significant differences in gestational age , cervical dilation , or incidence of ruptured membranes between groups at the initiation of tocolysis . Successful tocolysis was achieved in six of 16 patients receiving nitroglycerin , compared with 11 of 14 receiving magnesium sulfate ( 37.5 versus 78.6 % , P = .033 ) . Tocolytic failures ( nitroglycerin versus magnesium sulfate ) were due to persistent contractions with cervical change or rupture of previously intact membranes ( five of 16 versus two of 14 ) , persistent hypotension ( four of 16 versus none of 14 ) , and other severe side effects ( one of 16 versus one of 14 ) . Maternal hemodynamic alterations were more pronounced in patients who received nitroglycerin , and 25 % of patients assigned to nitroglycerin treatment had hypotension requiring discontinuation of therapy . CONCLUSION Tocolytic failures were more common with nitroglycerin than with magnesium sulfate . The hemodynamic alterations noted in patients receiving nitroglycerin , including a 25 % incidence of persistent hypotension , might limit the usefulness of IV nitroglycerin for the acute tocolysis of preterm labor |
13,899 | 22,837,391 | The results of this meta- analysis provide evidence that treatment with ALA ( 300 - 600 mg/day i.v .
for 2 - 4 weeks ) is safe and that the treatment can significantly improve both nerve conduction velocity and positive neuropathic symptoms . | OBJECTIVE To evaluate the effects and safety of 300 - 600 mg α-lipoic acid ( ALA ) given i.v .
for diabetic peripheral neuropathy ( DPN ) .
The treatment group involved the administration of ALA 300 - 600 mg i.v . | OBJECTIVE To evaluate the efficacy and safety of alpha-lipoic acid given intravenously , followed by oral treatment in type 2 diabetic patients with symptomatic polyneuropathy . RESEARCH DESIGN AND METHODS In a multicenter r and omized double-blind placebo-controlled trial ( Alpha-Lipoic Acid in Diabetic Neuropathy [ ALADIN ] III Study ) , 509 out patients were r and omly assigned to sequential treatment with 600 mg alpha-lipoic acid once daily intravenously for 3 weeks , followed by 600 mg alpha-lipoic acid three times a day orally for 6 months ( A-A ; n = 167 ) ; 600 mg alpha-lipoic acid once daily intravenously for 3 weeks , followed by placebo three times a day orally for 6 months ( A-P ; n = 174 ) ; and placebo once daily intravenously for 3 weeks , followed by placebo three times a day orally for 6 months ( P-P ; n = 168 ) . Outcome measures included the Total Symptom Score ( TSS ) for neuropathic symptoms ( pain , burning , paresthesias , and numbness ) in the feet , and the Neuropathy Impairment Score ( NIS ) . Data analysis was based on the intention to treat . RESULTS No significant differences between the groups were noted for the demographic variables and the nerve function parameters at baseline . The TSS in the feet decreased from baseline to day 19 ( median [ range ] ) by -3.7 ( -12.6 to 5.0 ) points in the group given alpha-lipoic acid intravenously and by -3.0 ( -12.3 to 8.0 ) points in the placebo group ( P = 0.447 ) , but the area under curve on a daily basis was significantly smaller in the active as compared with the placebo group ( 85.6 [ 0 - 219 ] vs. 95.9 [ 5.5 - 220 ] ) ; P = 0.033 ) . After 7 months , the changes in the TSS from baseline were not significantly different between the three groups studied , which could be due to increasing intercenter variability in the TSS during the trial . The NIS decreased after 19 days by -4.34+/-0.35 points ( mean + /- SEM ) in A-A and A-P and -3.49+/-0.58 points in P-P ( P = 0.02 for alpha-lipoic acid versus placebo ) and after 7 months by -5.82+/-0.73 points in A-A , -5.76+/-0.69 points in A-P , and -4.37+/-0.83 points in P-P ( P = 0.09 for A-A vs. P-P ) . The rates of adverse events were not different between the groups throughout the study . CONCLUSIONS These findings indicate that a 3-week intravenous treatment with alpha-lipoic acid , followed by a 6-month oral treatment , had no effect on neuropathic symptoms distinguishable from placebo to a clinical ly meaningful degree , possibly due to increasing intercenter variability in symptom scoring during the study . However , this treatment was associated with a favorable effect on neuropathic deficits without causing significant adverse reactions . Long-term trials that focus on neuropathic deficits rather than symptoms as the primary criterion of efficacy are needed to see whether oral treatment with alpha-lipoic acid over several years may slow or reverse the progression of diabetic neuropathy BACKGROUND Amelioration of insulin resistance could improve both glycaemic control and cardiovascular risk factors in patients with type 2 diabetes mellitus . Alpha-lipoic acid has been shown to improve insulin action after parenteral administration . OBJECTIVE the aim of the study was to assess the effect of oral administration of alpha-lipoic acid on insulin sensitivity in patients with type 2 diabetes . DESIGN twelve patients ( mean+/-sD ; age 52.9+/-9.9 yrs ; body mass index 33.9+/-7.4 kg/m(2 ) ) were treated with oral alpha-lipoic acid , 600 mg twice daily over a period of 4 weeks . twelve subjects with normal glucose tolerance served as a control group in terms of insulin sensitivity ( Is ) . Is was measured by a 2h manual hyperinsulinaemic ( insulin infusion rate-40 mU/m(2 ) body surface area/min ) euglycaemic ( blood glucose kept at 5 mmol/l ) clamp technique and expressed as a glucose disposal rate ( M ) and insulin sensitivity index ( IsI ) . RESULTS At the end of the treatment period , Is of diabetic patients was significantly increased : M from 3.202+/-1.898 to 5.951+/-2.705 mg/kg/min ( mean+/-sD ) , p<0.01 ; and IsI from 4.706+/-2.666 to 7.673+/-3.559 mg/kg/min per mIU/l x 100 ( mean+/-sD ) , p<0.05 . the difference was not statistically significant between the Is of diabetic patients after alpha-lipoic acid therapy and control subjects . CONCLUSION short-term oral alpha-lipoic acid treatment increases peripheral insulin sensitivity in patients with type 2 diabetes mellitus BACKGROUND The diabetic state , in both humans and experimental animals , is associated with oxidative stress . Lipid peroxidation of nerve membranes has been suggested as a mechanism by which peripheral nerve ischemia and hypoxia could cause neuropathy . Lipoic acid ( LA ) is a powerful inhibitor of iron-dependent lipid peroxidation and reactive oxygen species . The treatment of diabetic peripheral and cardiac autonomic neuropathy with LA is based on good clinical and experimental evidence . MATERIAL S AND METHODS To investigate the magnitude of the oxidative stress , serum ceruloplasmin ( Cp ) and lipid peroxide ( Lp ) levels were measured in 10 patients with diabetic neuropathy , before and 70 days after treatment with single dose of 600 mg LA/day . For other 12 healthy age- and sex-matched control subjects the serum Cp and Lp levels were evaluated . RESULTS Our results show that hyperglycemia is a factor for an increase in serum ceruloplasmin in patients with diabetic neuropathy compared to healthy subjects ( p < 0.0001 ) . High serum ceruloplasmin ( Cp ) level in patients with diabetes may be related to antioxidant defense . The treatment of diabetic neuropathy with LA does not affect significantly the serum Cp activity . The serum Lp levels after LA administration were significantly lower ( p < 0.005 ) than those before treatment . CONCLUSIONS The antioxidant therapy with LA improves and may prevent diabetic neuropathy . This improvement is associated with a reduction in the indexes of lipid peroxidation . Oxidative stress appears to be primarily due to the processes of nerve ischemia and hyperglycemia autooxidation Diabetic polyneuropathy is a serious complication in patients with diabetes mellitus . In addition to the maintenance of a sufficient metabolic control , alpha-lipoic acid ( ALA ) ( Thioctacid , Asta Medica ) is known to have beneficial effects on diabetic polyneuropathy although the exact mechanism by which ALA exerts its effect is unknown . In order to study the effect of ALA on microcirculation in patients with diabetes mellitus and peripheral neuropathy one group of patients ( 4 female , 4 male , age 60+/-3 years , diabetes duration 19+/-4 years , BMI 24.8+/-1.3 kg/m2 ) received 1200 mg ALA orally per day over 6 weeks ( trial 1 ) . A second group of patients ( 5 female , 4 male , age 65+/-3 years , diabetes duration 14+/-4 years , BMI 23.6+/-0.7 kg/m2 ) was studied before and after they had received 600 mg ALA or placebo intravenously over 15 minutes in order to investigate whether ALA has an acute effect on microcirculation ( trial 2 ) . Patients were investigated by nailfold video-capillaroscopy . Capillary blood cell velocity was examined at rest and during postreactive hyperemia ( occlusion of the wrist for 2 minutes , 200 mmHg ) which is a parameter of the perfusion reserve on dem and . The oral therapy with ALA result ed in a significant decrease in the time to peak capillary blood cell velocity ( tpCBV ) during postocclusive hyperemia ( trial 1 : 12.6+/-3.1 vs 35.4+/-10.9 s , p<0.05 ) . The infusion of ALA also decreased the tpCBV in patients with diabetic neuropathy ( trial 2 : before : 20.8+/-4,5 , ALA : 11.74+/-4.4 , placebo : 21.9 - 5.0 s , p<0.05 ALA vs both placebo and before infusions ) indicating that ALA has an acute effect on microcirculation . Capillary blood cell velocity at rest ( rCBV ) , hemodynamic parameters , hemoglobinA1c and local skin temperature remained unchanged in both studies . These results demonstrate that in patients with diabetic polyneuropathy ALA improves microcirculation as indicated by an increased perfusion reserve on dem and . The observed effects are apparently acute effects . With the restriction of the pilot character of this investigation the findings support the assumption that ALA might exert its beneficial effects at least partially by improving microcirculation which is likely to occur also at the level of the vasa nervorum OBJECTIVE —The aim of this trial was to evaluate the effects of α-lipoic acid ( ALA ) on positive sensory symptoms and neuropathic deficits in diabetic patients with distal symmetric polyneuropathy ( DSP ) . RESEARCH DESIGN AND METHODS —In this multicenter , r and omized , double-blind , placebo-controlled trial , 181 diabetic patients in Russia and Israel received once-daily oral doses of 600 mg ( n = 45 ) ( ALA600 ) , 1,200 mg ( n = 47 ) ( ALA1200 ) , and 1,800 mg ( ALA1800 ) of ALA ( n = 46 ) or placebo ( n = 43 ) for 5 weeks after a 1-week placebo run-in period . The primary outcome measure was the change from baseline of the Total Symptom Score ( TSS ) , including stabbing pain , burning pain , paresthesia , and asleep numbness of the feet . Secondary end points included individual symptoms of TSS , Neuropathy Symptoms and Change ( NSC ) score , Neuropathy Impairment Score ( NIS ) , and patients ’ global assessment of efficacy . RESULTS —Mean TSS did not differ significantly at baseline among the treatment groups and on average decreased by 4.9 points ( 51 % ) in ALA600 , 4.5 ( 48 % ) in ALA1200 , and 4.7 ( 52 % ) in ALA1800 compared with 2.9 points ( 32 % ) in the placebo group ( all P < 0.05 vs. placebo ) . The corresponding response rates ( ≥50 % reduction in TSS ) were 62 , 50 , 56 , and 26 % , respectively . Significant improvements favoring all three ALA groups were also noted for stabbing and burning pain , the NSC score , and the patients ’ global assessment of efficacy . The NIS was numerically reduced . Safety analysis showed a dose-dependent increase in nausea , vomiting , and vertigo . CONCLUSIONS —Oral treatment with ALA for 5 weeks improved neuropathic symptoms and deficits in patients with DSP . An oral dose of 600 mg once daily appears to provide the optimum risk-to-benefit ratio Aims To evaluate the efficacy and safety of short‐term oral treatment with the antioxidant thioctic acid ( TA ) on neuropathic symptoms and deficits in patients with Type 2 diabetes mellitus with symptomatic polyneuropathy Anti-oxidant treatment has been shown to prevent nerve dysfunction in experimental diabetes mellitus , thus providing a rationale of potential therapeutic value for diabetic patients . The effects of the anti-oxidant alpha-lipoic acid ( thioctic acid ) were studied in a 3-week multicentre , r and omized , double-blind placebo-controlled trial ( Alpha-Lipoic Acid in Diabetic Neuropathy ; ALADIN ) in 328 non-insulin-dependent diabetic patients with symptomatic peripheral neuropathy who were r and omly assigned to treatment with intravenous infusion of alpha-lipoic acid using three doses ( 1200 , 600 , or 100 mg ALA ) or placebo ( PLAC ) . Neuropathic symptoms ( pain , burning , paraesthesiae , and numbness ) were scored at baseline and at each visit ( days 2 - 5 , 8 - 12 , and 15 - 19 ) prior to infusion . In addition , the Hamburg Pain Adjective List , a multidimensional specific pain question naire , and the Neuropathy Symptom and Disability Scores were assessed at baseline and day 19 . According to the protocol 260 ( 65/63/66/66 ) patients completed the study . The total symptom score in the feet decreased from baseline to day 19 by -4.5 + /- 3.7 ( -58.6 % ) points ( mean + /- SD ) in ALA 1200 , -5.0 + /- 4.1 ( -63.5 % ) points in ALA 600 , -3.3 + /- 2.8 ( -43.2 % ) points in ALA 100 , and -2.6 + /- 3.2 ( -38.4 % ) points in PLAC ( ALA 1200 vs PLAC : p = 0.003 ; ALA 600 vs PLAC : p < 0.001 ) . The response rates after 19 days , defined as an improvement in the total symptom score of at least 30 % , were 70.8 % in ALA 1200 , 82.5 % in ALA 600 , 65.2 % in ALA 100 , and 57.6 % in PLAC ( ALA 600 vs PLAC ; p = 0.002 ) . The total scale of the Pain Adjective List was significantly reduced in ALA 1200 and ALA 600 as compared with PLAC after 19 days ( both p < 0.01 ) . The rates of adverse events were 32.6 % in ALA 1200 , 18.2 % in ALA 600 , 13.6 % in ALA 100 , and 20.7 % in PLAC . These findings substantiate that intravenous treatment with alpha-lipoic acid using a dose of 600 mg/day over 3 weeks is superior to placebo in reducing symptoms of diabetic peripheral neuropathy , without causing significant adverse reactions Short-term trials with the antioxidant thioctic acid ( TA ) appear to improve neuropathic symptoms in diabetic patients , but the long-term response remains to be established . Therefore , Type 1 and Type 2 diabetic patients with symptomatic polyneuropathy were r and omly assigned to three treatment regimens : ( 1 ) 2 x 600(mg of TA ( TA 1200 ) , ( 2 ) 600)mg of TA plus placebo ( PLA ) ( TA 600 ) or ( 3 ) placebo and placebo ( PLA ) . A trometamol salt solution of TA of 1200 or 600 mg or PLA was intravenously administered once daily for five consecutive days before enrolling the patients in the oral treatment phase . The study was prospect i ve , PLA-controlled , r and omized , double-blind and conducted for two years . Severity of diabetic neuropathy was assessed by the Neuropathy Disability Score ( NDS ) and electrophysiological attributes of the sural ( sensory nerve conduction velocity ( SNCV ) , sensory nerve action potential ( SNAP ) ) and the tibial ( motor nerve conduction velocity ( MNCV ) , motor nerve distal latency ( MNDL ) ) nerve . Statistical analysis was performed after independent review ers excluded all patients with highly variable data allowing a final analysis of 65 patients ( TA 1200 : n = 18 , TA 600 : n = 27 ; PLA : n = 20 ) . At baseline no significant differences were noted between the groups regarding the demographic variables and peripheral nerve function parameters for these 65 patients . Statistically significant changes after 24 months between TA and PLA were observed ( mean + /- SD ) for sural SNCV : + 3.8 + /- 4.2 m/s in TA 1200 , + 3.0+/-3.0 m/s in TA 600 , -0.1+/-4.8 m/s in PLA ( p < 0.05 for TA 1200 and TA 600 vs. PLA ) ; sural SNAP : + 0.6+/-2.5 microV in TA 1200 , + 0.3+/-1.4 microV in TA 600 , -0.7 + /- 1.5 microV in PLA ( p = 0.076 for TA 1200 vs. PLA and p < 0.05 for TA 600 vs. PLA ) , and in tibial MNCV : + /- 1.2 + /- 3.8 m/s in TA 1200 , -0.3 + /- 5.2 m/s in TA 600 , 1.5 + /- 2.9 m/s in PLA ( p < 0.05 for TA 1200 vs. PLA ) . No significant differences between the groups after 24 months were noted regarding the tibial MNDL and the NDS . We conclude that in a subgroup of patients after exclusion of patients with excessive test variability throughout the trial , TA appeared to have a beneficial effect on several attributes of nerve conduction OBJECTIVE Because alpha-lipoic acid ( ALA ) , a potent antioxidant , prevents or improves nerve conduction attributes , endoneurial blood flow , and nerve ( Na(+ ) K(+ ) ATPase activity in experimental diabetes and in humans and may improve positive neuropathic sensory symptoms , in this report we further assess the safety and efficacy of ALA on the Total Symptom Score ( TSS ) , a measure of positive neuropathic sensory symptoms . RESEARCH DESIGN AND METHODS Metabolically stable diabetic patients with symptomatic ( stage 2 ) diabetic sensorimotor polyneuropathy ( DSPN ) were r and omized to a parallel , double-blind study of ALA ( 600 mg ) ( n = 60 ) or placebo ( n = 60 ) infused daily intravenously for 5 days/week for 14 treatments . The primary end point was change of the sum score of daily assessment s of severity and duration of TSS . Secondary end points were sum scores of neuropathy signs ( NIS ) , symptoms ( NSC ) , attributes of nerve conduction , quantitative sensation tests ( QSTs ) , and an autonomic test . RESULTS At r and omization , the groups were not significantly different by the criteria of metabolic control or neuropathic end points . After 14 treatments , the TSS of the ALA group had improved from baseline by an average of 5.7 points and the placebo group by an average of 1.8 points ( P < 0.001 ) . Statistically significant improvement from baseline of the ALA , as compared with the placebo group , was also found for each item of the TSS ( lancinating and burning pain , asleep numbness and prickling ) , NIS , one attribute of nerve conduction , and global assessment of efficacy . CONCLUSIONS Intravenous racemic ALA , a potent antioxidant , rapidly and to a significant and meaningful degree , improved such positive neuropathic sensory symptoms as pain and several other neuropathic end points . This improvement of symptoms was attributed to improved nerve pathophysiology , not to increased nerve fiber degeneration . Because of its safety profile and its effect on positive neuropathic sensory symptoms and other neuropathic end points , this drug appears to be a useful ancillary treatment for the symptoms of diabetic polyneuropathy |
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